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Leaflet TRODELVY 200mg powder for concentrate for solution for infusion
- Product code:
- W68365001
- Quantity:
- 1
- Indicated for:
- breast cancer
- Route of administration:
- infusion
- Substance:
- sacituzumab govitecan (antibody-drug conjugate)
- ATC
- L01FX17 — Antineoplastic and immunomodulating agents | Monoclonal antibodies and antibody drug conjugates | Other monoclonal antibodies and antibody drug conjugates
Sacituzumab govitecan is an antibody-drug conjugate used in the treatment of metastatic triple-negative breast cancer (TNBC) and other advanced cancers. It consists of a monoclonal antibody targeting the Trop-2 protein, which is frequently expressed on the surface of tumor cells, and a chemotherapeutic agent (SN-38) that is directly delivered into cancer cells.
Sacituzumab govitecan is administered intravenously, usually once weekly, and is indicated for patients with TNBC who have previously received at least two lines of systemic therapy. It is used to reduce tumor size, slow disease progression, and improve overall survival.
Common side effects include nausea, diarrhea, fatigue, alopecia, and neutropenia. In rare cases, severe adverse reactions such as hypersensitivity reactions or hematologic toxicity may occur. Regular monitoring of hematologic parameters and liver function is essential.
Sacituzumab govitecan represents an innovative therapeutic option for patients with advanced cancer, offering a targeted and effective approach to treating aggressive tumors.
Sacituzumab govitecan is administered intravenously, usually once weekly, and is indicated for patients with TNBC who have previously received at least two lines of systemic therapy. It is used to reduce tumor size, slow disease progression, and improve overall survival.
Common side effects include nausea, diarrhea, fatigue, alopecia, and neutropenia. In rare cases, severe adverse reactions such as hypersensitivity reactions or hematologic toxicity may occur. Regular monitoring of hematologic parameters and liver function is essential.
Sacituzumab govitecan represents an innovative therapeutic option for patients with advanced cancer, offering a targeted and effective approach to treating aggressive tumors.
General data about TRODELVY 200mg
- Substance:
- sacituzumab govitecan
- Date of latest medicines list:
- 01-09-2026
- Product code:
- W68365001
- Concentration:
- 200mg
- Pharmaceutical form:
- powder for concentrate for solution for infusion
- Quantity:
- 1
- Product type:
- Original
- Price:
- 5444.00 RON
- Prescription status:
- P-RF — Medicines dispensed with a medical prescription that is retained by the pharmacy and cannot be renewed.
Official documents
- Added to database:
- 24/11/2021
- Source record updated:
- 15/09/2026
Precautions:
Additional monitoring
This medicine is subject to additional monitoring.
Contents of the package leaflet for the medicine TRODELVY 200mg powder for concentrate for solution for infusion
Find in leaflet
Leaflet TRODELVY 200mg
1. NAME OF THE MEDICINAL PRODUCT
Trodelvy 200 mg powder for concentrate for solution for infusion.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
One vial of powder contains 200 mg sacituzumab govitecan.
After reconstitution, one mL of solution contains 10 mg sacituzumab govitecan.
Sacituzumab govitecan is a Trop-2-directed antibody-drug conjugate (ADC). Sacituzumab is ahumanised monoclonal antibody (hRS7 IgG1κ) that recognises Trop-2. The small molecule, SN-38, isa topoisomerase I inhibitor, which is covalently attached to the antibody by a hydrolysable linker.
Approximately 7-8 molecules of SN-38 are attached to each antibody molecule.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Powder for concentrate for solution for infusion.
Off-white to yellowish powder.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Triple-Negative Breast Cancer
Trodelvy is indicated:
* in combination with pembrolizumab, for the treatment of adult patients with unresectablelocally advanced or metastatic triple-negative breast cancer (TNBC) who have not receivedprior systemic therapy for metastatic disease and whose tumours express PD-L1 with acombined positive score (CPS) ≥ 10 (see sections 4.2 and 5.1).
* as monotherapy for the treatment of adult patients with unresectable locally advanced ormetastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapyfor metastatic disease and who are not candidates for PD-1 or PD-L1 inhibitor therapy (seesection 5.1).
* as monotherapy for the treatment of adult patients with unresectable or metastatic TNBC whohave received two or more prior systemic therapies, including at least one of them for advanceddisease (see section 5.1)
HR-Positive, HER2-Negative Breast Cancer
Trodelvy as monotherapy is indicated for the treatment of adult patients with unresectable ormetastatic hormone receptor (HR)-positive, HER2-negative breast cancer who have receivedendocrine-based therapy, and at least two additional systemic therapies in the advanced setting (seesection 5.1).
4.2 Posology and method of administration
Trodelvy must only be prescribed and administered to patients by healthcare professionals experiencedin the use of anti-cancer therapies and administered in an environment where full resuscitationfacilities are available.
Patient Selection
PD-L1 testing for treatment with sacituzumab govitecan in combination with pembrolizumab shouldbe assessed by a CE-marked in vitro diagnostic (IVD) intended for use with pembrolizumab. If the
CE-marked IVD is not available, an alternative validated test should be used (see sections 4.1 and 5.1).
PosologyThe recommended dose of sacituzumab govitecan as monotherapy or in combination withpembrolizumab is 10 mg/kg body weight administered as an intravenous infusion once weekly on Day1 and Day 8 of 21-day treatment cycles. Treatment should be continued until disease progression orunacceptable toxicity.
Patients should be administered sacituzumab govitecan before pembrolizumab when given on thesame day.
Refer to the pembrolizumab Summary of Product Characteristics (SmPC) for dosing information onpembrolizumab.
Prevention treatment
Prior to each dose of sacituzumab govitecan, treatment for prevention of infusion-related reactions andprevention of chemotherapy-induced nausea and vomiting (CINV) is recommended (see section 4.4).
Prophylaxis for neutropenia
Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) should be consideredstarting in the first cycle in patients at increased risk of febrile neutropenia (see section 4.4).
Dose modifications for adverse reactions for sacituzumab govitecan
Management of adverse reactions may require temporary interruption, dose reduction, or treatmentdiscontinuation of sacituzumab govitecan. The recommended dose reduction schedule is presented in
Table 1 and the recommended dose modifications for adverse reactions are provided in Table 2. Thesacituzumab govitecan dose should not be re-escalated after a dose reduction for adverse reactions hasbeen made.
Table 1: Dose reduction schedule
Dose reduction schedule Dose level
Recommended starting dose 10 mg/kg
First dose reduction Reduce to 7.5 mg/kg
Second dose reduction Reduce to 5 mg/kg
Requirement for further dose reduction Discontinue treatment
Table 2: Recommended dose modifications for adverse reactions
Adverse reactions Severity Dose modification
Neutropenia * Grade 3-4 neutropenia * Withhold treatment until resolved to(Absolute Neutrophil Count ≤ Grade 1 (ANC ≥ 1500/mm3) for[ANC]<1000/mm3) Day 1 dose or Grade 2 (ANC
* Grade 3-4 febrile ≥ 1000/mm3) for Day 8 dose (seeneutropenia section 4.4).(ANC<1000/mm3) * Administer G-CSF during treatment asclinically indicated.
* For subsequent Grade 3-4 febrileneutropenia events or subsequentprolonged Grade 3-4 neutropenia events,reduce one dose level with eachrecurrence or discontinue according to
Table 1.
Nausea/Vomiting/ * Grade 3-4 nausea, vomiting * Withhold treatment until resolved to
Diarrhoea or diarrhoea due to treatment ≤ Grade 1 (see section 4.4).
that is not controlled with * Reduce one dose level with eachantiemetics and anti- occurrence or discontinue according todiarrheal agents Table 1.
Infusion-related * Grade 1-3 infusion-related * Slow or interrupt the infusion rate ofreaction reactions sacituzumab govitecan
* Grade 4 infusion-related * Discontinue treatmentreactions
Other Toxicities * Other Grade 3-4 toxicities of * Withhold treatment until resolved toany duration despite optimal ≤ Grade 1.medical management * Reduce one dose level with eachoccurrence or discontinue according to
Table 1.
Dose modifications for adverse reactions for sacituzumab govitecan in combination withpembrolizumab
When sacituzumab govitecan is administered in combination with pembrolizumab, treatment with oneor both medicines should either be interrupted, discontinued or the dose of sacituzumab govitecanshould be reduced to manage adverse reactions as appropriate, as described in Table 1 and Table 2.
For recommendations for management of adverse reactions of pembrolizumab, refer to thepembrolizumab SmPC.
Special populationsElderly
No dose adjustment is required in patients ≥ 65 years old. Data from sacituzumab govitecan in patients≥ 75 years are limited.
Hepatic impairmentNo adjustment to the starting dose is required when administering sacituzumab govitecan to patientswith mild hepatic impairment (bilirubin ≤ 1.5 upper limit of normal [ULN] and aspartateaminotransferase [AST]/alanine aminotransferase [ALT] < 3 ULN).
The safety of sacituzumab govitecan in patients with moderate or severe hepatic impairment has notbeen established. Sacituzumab govitecan has not been studied in patients with any of the following:serum bilirubin > 1.5 ULN, or AST or ALT > 3 ULN in patients without liver metastases, or AST or
ALT > 5 ULN in patients with liver metastases. The use of sacituzumab govitecan should be avoidedin these patients.
Renal impairmentNo adjustment to the starting dose is required when administering sacituzumab govitecan to patientswith mild or moderate renal impairment.
Sacituzumab govitecan has not been studied in patients with severe renal impairment or end-stagerenal disease (Creatinine Clearance [CrCl] < 15 mL/min).
Paediatric populationThe safety and efficacy of sacituzumab govitecan in children aged 0 to 18 years have not beenestablished. No data are available.
Method of administrationSacituzumab govitecan is for intravenous use only. It must be reconstituted and diluted by a healthcareprofessional experienced in the handling of anti-cancer therapies. It must be administered as anintravenous infusion, not as an intravenous push or bolus.
First infusion: the infusion should be administered over a period of 3 hours.
Subsequent infusions: the infusion should be administered over a period of 1 to 2 hours if priorinfusions were tolerated.
Patients have to be observed during each infusion and for at least 30 minutes after each infusion forsigns or symptoms of infusion-related reactions (see section 4.4).
For instructions on reconstitution and dilution of the medicinal product before administration, seesection 6.6.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Traceability
In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.
NeutropeniaSacituzumab govitecan can cause severe or life-threatening neutropenia (see section 4.8). Fatalinfections in the setting of neutropenia have been observed in clinical studies with sacituzumabgovitecan, primarily in the first two cycles of treatment.
Primary prophylaxis with G-CSF should be considered starting in the first cycle of treatment inpatients at increased risk of febrile neutropenia, e.g., older patients (in particular aged 65 years andolder), patients with previous neutropenia, poor performance status, organ dysfunction (includingrenal, liver or cardiovascular dysfunction), or multiple comorbid conditions. Monitor ANC duringtreatment.
Sacituzumab govitecan should not be administered if the ANC is below 1500/mm3 on Day 1 of anycycle or if the neutrophil count is below 1000/mm3 on Day 8 of any cycle. Sacituzumab govitecanshould not be administered in case of neutropenic fever. Dose modifications may be required due toneutropenia or febrile neutropenia. Treat neutropenia with G-CSF and consider prophylaxis insubsequent cycles as clinically indicated (see sections 4.2 and 4.8).
DiarrhoeaSacituzumab govitecan can cause severe diarrhoea (see section 4.8). Diarrhoea in some cases wasobserved to have led to dehydration and subsequent acute kidney injury. Sacituzumab govitecanshould not be administered in case of Grade 3-4 diarrhoea at the time of scheduled treatment andtreatment should only be continued when resolved to ≤ Grade 1 (see section 4.2 and 4.8). At the onsetof diarrhoea, and if no infectious cause can be identified, treatment with loperamide should beinitiated. Additional supportive measures (e.g. fluid and electrolyte substitution) may also beemployed as clinically indicated.
Patients who exhibit an excessive cholinergic response to treatment with sacituzumab govitecan (e.g.abdominal cramping, diarrhoea, salivation, etc.) can receive appropriate treatment (e.g. atropine) forsubsequent treatments with sacituzumab govitecan.
HypersensitivitySacituzumab govitecan can cause severe and life-threatening hypersensitivity (see section 4.8).
Anaphylactic reactions have been observed in clinical studies with sacituzumab govitecan and the useof sacituzumab govitecan is contraindicated in patients with a known hypersensitivity to sacituzumabgovitecan (see section 4.3).
Pre-infusion treatment, including antipyretics, H1 and H2 blockers, or corticosteroids (e.g. 50 mghydrocortisone or equivalent, orally or intravenously), for patients receiving sacituzumab govitecan isrecommended. Patients should be closely observed for infusion-related reactions during eachsacituzumab govitecan infusion and for at least 30 minutes after completion of each infusion. Theinfusion rate of sacituzumab govitecan should be slowed down or infusion interrupted if the patientdevelops an infusion-related reaction. Sacituzumab govitecan should be permanently discontinued iflife-threatening infusion-related reactions occur (see section 4.2).
Nausea and vomiting
Sacituzumab govitecan is emetogenic (see section 4.8). Antiemetic preventive treatment with two orthree medicinal products (e.g. dexamethasone with either a 5-hydroxytryptamine 3 [5-HT3] receptorantagonist or a Neurokinin-1 [NK-1] receptor antagonist as well as other medicinal products asindicated) is recommended for prevention of chemotherapy-induced nausea and vomiting (CINV).
Sacituzumab govitecan should not be administered in case of Grade 3 nausea or Grade 3-4 vomiting atthe time of scheduled treatment administration and treatment should only be continued with additionalsupportive measures when resolved to ≤ Grade 1 (see section 4.2). Additional antiemetics and othersupportive measures may also be employed as clinically indicated. All patients should be given take-home medicinal products with clear instructions for prevention and treatment of nausea and vomiting.
Use in patients with reduced UGT1A1 activity
SN-38 (the small molecule moiety of sacituzumab govitecan) is metabolised via uridinediphosphate-glucuronosyl transferase (UGT1A1). Genetic variants of the UGT1A1 gene such as the
UGT1A1*28 allele lead to reduced UGT1A1 enzyme activity. Individuals who are homozygous for
UGT1A1*28 allele are at increased risk for neutropenia, febrile neutropenia, and anaemia and are atincreased risk for other adverse reactions following initiation of sacituzumab govitecan treatment (seesection 4.8). A higher incidence of Grade 3-4 neutropenia, febrile neutropenia, and anaemia wasobserved in patients homozygous for the UGT1A1*28 allele and patients heterozygous for the
UGT1A1*6 allele compared to patients homozygous for the wild-type allele. Approximately 20% ofthe Black population, 10% of the White population, and 2% of the East Asian population arehomozygous for the UGT1A1*28 allele. Approximately 0.2% of the Black population, 0.3% of the
White population, and 27% of the East Asian population are heterozygous for the UGT1A1*6 allele.
Variants in other alleles potentially associated with reduced UGT1A1 enzyme activities might beprevalent in certain populations. Patients with known reduced UGT1A1 activity should be closelymonitored for adverse reactions. When unknown, no testing of UGT1A1 status is required as themanagement of adverse reactions including the recommended dose modifications will be the same forall patients.
Embryo-foetal toxicity
Based on its mechanism of action, sacituzumab govitecan can cause teratogenicity and/orembryo-foetal lethality when administered to a pregnant woman. Sacituzumab govitecan contains agenotoxic component, SN-38, and targets rapidly dividing cells. Pregnant women and women ofchildbearing potential should be informed of the potential risk to the foetus. The pregnancy status offemales of reproductive potential should be verified prior to the initiation of sacituzumab govitecan(see section 4.6).
SodiumThis medicinal product will be further prepared for administration with sodium-containing solution(see section 6.6) and this should be considered in relation to the total sodium intake to the patient fromall sources per day.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
UGT1A1 inhibitors
Concomitant administration of sacituzumab govitecan with inhibitors of UGT1A1 may increase theincidence of adverse reactions due to potential increase in systemic exposure to SN-38. Sacituzumabgovitecan should be used with caution in patients receiving UGT1A1 inhibitors (e.g. propofol,ketoconazole, EGFR tyrosine kinase inhibitors).
UGT1A1 inducers
Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers.
Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inducers (e.g.carbamazepine, phenytoin, rifampicin, ritonavir, tipranavir).
Based on the limited data available from patients who received UGT1A1 inhibitors (n=15) or inducers(n=7) while being treated with sacituzumab govitecan, free SN-38 exposures in these patients werecomparable to those in patients who did not receive UGT1A1 inhibitor or inducer.
4.6 Fertility, pregnancy and lactation
Women of childbearing potential/Contraception in males and females
Women of childbearing potential have to use effective contraception during treatment and for6 months after the last dose.
Male patients with female partners of childbearing potential have to use effective contraception duringtreatment with sacituzumab govitecan and for 3 months after the last dose.
PregnancyThere are no available data on the use of sacituzumab govitecan in pregnant women. However, basedon its mechanism of action, sacituzumab govitecan can cause teratogenicity and/or embryo-foetallethality when administered during pregnancy. Sacituzumab govitecan contains a genotoxiccomponent, SN-38, and targets rapidly dividing cells.
Sacituzumab govitecan should not be used during pregnancy unless the clinical condition of thewoman requires treatment with sacituzumab govitecan.
The pregnancy status of women of childbearing potential should be verified prior to the initiation ofsacituzumab govitecan.
Women who become pregnant must immediately contact their doctor.
Breast-feedingIt is unknown whether sacituzumab govitecan or its metabolites are excreted in human milk. A risk tobreastfed newborns/infants cannot be excluded. Breast-feeding should be discontinued duringtreatment with sacituzumab govitecan and for 1 month after the last dose.
FertilityBased on findings in animals, sacituzumab govitecan may impair fertility in females of reproductivepotential (see section 5.3). No human data on the effect of sacituzumab govitecan on fertility areavailable.
4.7 Effects on ability to drive and use machines
Sacituzumab govitecan has minor influence on the ability to drive and use machines, e.g. dizziness,fatigue (see section 4.8).
4.8 Undesirable effects
Summary of the safety profile
Sacituzumab govitecan as monotherapy
The most common adverse reactions reported in patients treated with sacituzumab govitecan were:neutropenia (67.3%), nausea (62.1%), diarrhoea (59.9%), fatigue (57.4%), alopecia (48.3%),anaemia (40.1%), constipation (36.7%), vomiting (31.3%), and decreased appetite (23.3%).
The most common grade 3 or higher adverse reactions were neutropenia (48.6%), diarrhoea (10.0%),leukopenia (9.6%), anaemia (7.7%), fatigue (5.8%), febrile neutropenia (5.6%), and lymphopenia(3.1%).
The most frequently reported serious adverse reactions in patients treated with sacituzumab govitecanwere febrile neutropenia (4.5%), diarrhoea (3.7%), neutropenia (2.9%) and pneumonia (2.1%).
Sacituzumab govitecan in combination with pembrolizumab
Adverse reactions occurring in patients treated with sacituzumab govitecan in combination withpembrolizumab were generally similar to those observed with sacituzumab govitecan orpembrolizumab in breast cancer treatment. The most frequent adverse reactions in patients treated withsacituzumab govitecan in combination with pembrolizumab were diarrhoea (70.1%), nausea (67.9%),neutropenia (62.9%), fatigue (58.4%), alopecia (51.6%), constipation (40.7%), anaemia (36.7%) andvomiting (29.4%), and the most frequent grade 3 or higher adverse reactions were neutropenia (43.0%)and diarrhoea (10.0%).
The combination of sacituzumab govitecan with pembrolizumab did not increase the frequency orseverity of pembrolizumab-associated immune-mediated adverse reactions.
When sacituzumab govitecan is administered in combination with pembrolizumab, refer to the SmPCfor the respective combination therapy components prior to initiation of treatment. Adverse reactionsknown to occur with sacituzumab govitecan or combination therapy components given alone mayoccur during treatment with these medicinal products in combination, even if these reactions were notreported in clinical studies with combination therapy.
Tabulated list of adverse reactionsThe frequencies of adverse reactions are based on pooled data from four clinical studies involving963 patients who received sacituzumab govitecan 10 mg/kg body weight for the treatment ofmetastatic TNBC and HR+/HER2- breast cancer. The median exposure to sacituzumab govitecan inthis data set was 5.29 months.
The safety of sacituzumab govitecan in combination with pembrolizumab has also been evaluated in aclinical study of 221 patients with metastatic TNBC whose tumours express PD-L1 receivingsacituzumab govitecan 10 mg/kg on Days 1 and 8 and pembrolizumab 200 mg on Day 1 of a 21-daycycle. The median exposure of sacituzumab govitecan in the combination therapy data set was 8.9months.
Adverse reactions observed in clinical studies of sacituzumab govitecan as monotherapy or incombination with pembrolizumab or reported from post-marketing use of sacituzumab govitecan arelisted in Table 3. The adverse reaction frequencies are based on all-cause adverse event frequencies,where a proportion of the events for an adverse reaction may have other causes than sacituzumabgovitecan, such as the disease, other medicinal products or unrelated causes. The severity of adversedrug reactions was assessed based on the Common Terminology Criteria for Adverse Events(CTCAE), defining grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening,and 5 = death.
Adverse reactions are listed by System Organ Class and frequency category. Frequency categories aredefined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100);rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); and not known (cannot be estimated from theavailable data). Within each frequency grouping, adverse reactions are presented in the order ofdecreasing seriousness.
Table 3: List of adverse reactions
System organ class Monotherapy In combination with pembrolizumab(SOC) and
Frequency
Infections and infestationsVery common Urinary tract infection Urinary tract infection
Upper respiratory tract infection Upper respiratory tract infection
Common Sepsis Sepsis
Pneumonia Pneumonia
Influenza Influenza
Bronchitis Bronchitis
Nasopharyngitis Nasopharyngitis
Sinusitis Sinusitis
Oral herpes Oral herpes
Blood and lymphatic system disordersVery common Neutropenia1 Neutropenia1
Anaemia2 Anaemia2
Leukopenia3 Leukopenia3
Lymphopenia4
Common Febrile neutropenia Febrile neutropenia
Thrombocytopenia5 Lymphopenia4
Thrombocytopenia5
Immune system disordersVery common Hypersensitivity6 Hypersensitivity6
System organ class Monotherapy In combination with pembrolizumab(SOC) and
Frequency
Metabolism and nutrition disordersVery common Decreased appetite Decreased appetite
HypokalaemiaHypomagnesaemia
Common Dehydration Dehydration
Hyperglycaemia Hyperglycaemia
Hypophosphataemia Hypokalaemia
Hypocalcaemia Hypomagnesaemia
Hyponatraemia Hypophosphataemia
HypocalcaemiaHyponatraemia
Psychiatric disordersCommon Insomnia Insomnia
Anxiety Anxiety
Nervous system disordersVery common Headache Headache
Dizziness Dizziness
Common Dysgeusia Dysgeusia
Vascular disordersCommon Hypotension Hypotension
Respiratory, thoracic and mediastinal disordersVery common Dyspnoea7 Cough
Cough
Common Epistaxis Dyspnoea7
Productive cough Epistaxis
Rhinorrhoea Productive cough
Nasal congestion Rhinorrhoea
Upper airway cough syndrome Nasal congestion
Uncommon Upper airway cough syndrome
Gastrointestinal disordersVery common Diarrhoea Diarrhoea
Vomiting Vomiting
Constipation Constipation
Stomatitis Stomatitis
Nausea Nausea
Abdominal pain Abdominal Pain
Common Neutropenic colitis8 Colitis
Colitis Abdominal pain upper
Abdominal pain upper Dyspepsia
Dyspepsia Gastrooesophageal reflux disease
Gastrooesophageal reflux disease Abdominal distension
Abdominal distension
Uncommon Enteritis Neutropenic colitis8
Enteritis
Skin and subcutaneous tissue disordersVery common Alopecia Alopecia
Rash Rash
Pruritus Pruritus
Common Rash maculopapular Rash maculopapular
Skin hyperpigmentation Skin hyperpigmentation
Dermatitis acneiform Dermatitis acneiform
Dry skin Dry skin
Musculoskeletal and connective tissue disordersVery common Back pain Back pain
Arthralgia Arthralgia
Common Musculoskeletal chest pain Musculoskeletal chest pain
Muscle spasms Muscle spasms
System organ class Monotherapy In combination with pembrolizumab(SOC) and
Frequency
Renal and urinary disordersCommon Haematuria Haematuria
Proteinuria Proteinuria
Dysuria Dysuria
General disorders and administration site conditionsVery common Fatigue9 Fatigue9
Common Pain Pain
Chills Chills
InvestigationsVery common Blood alkaline phosphatase increased Weight decreased
Blood alkaline phosphatase increased
Common Weight decreased Blood lactate dehydrogenase increased
Activated partial thromboplastin timeprolonged
Blood lactate dehydrogenase increased
Injury, poisoning and procedural complicationsCommon Infusion related reaction Infusion related reaction1: Includes the following preferred terms: neutropenia; neutrophil count decreased.2: Includes the following preferred terms: anaemia; haemoglobin decreased; red blood cell count decreased.3: Includes the following preferred terms: leukopenia; white blood cell count decreased.4: Includes the following preferred terms: lymphopenia; lymphocyte count decreased.5: Includes the following preferred terms: thrombocytopenia; platelet count decreased.6: Hypersensitivity events reported up to the end of the day after treatment was administered. Includes events coded to thefollowing preferred terms: rash, infusion related reaction, hypersensitivity, periorbital oedema, catheter site dermatitis,contrast media reaction, dermatitis allergic, dermatitis contact, eczema, rash erythematous, urticaria, anaphylactic reaction,bronchospasm, conjunctivitis allergic, dermatitis, dermatitis acneiform, dermatitis exfoliative generalised, drughypersensitivity, infusion related hypersensitivity reaction, rash macular, rash maculo-papular, rash papular, rash pustular,rhinitis allergic, swelling face, swelling of eyelid, swollen tongue, Type IV hypersensitivity reaction, cough with pruritus,cough with rash, dyspnoea with pruritus, dyspnoea with rash, dyspnoea with wheezing and rash, hypotension withdyspnoea7: Includes the following preferred terms: dyspnoea; dyspnoea exertional8: Includes the preferred term of neutropenic colitis and events reported as typhlitis9: Includes the following preferred terms: fatigue, asthenia
Description of selected adverse reactionsThe data below reflect information for significant adverse reactions for sacituzumab govitecan asmonotherapy in clinical trials (see section 5.1). The management guidelines for these adverse reactionsare described in sections 4.2 and 4.4.
NeutropeniaThe median time to onset of neutropenia (including febrile neutropenia) following the start of the firsttreatment cycle was 20 days. The median duration of neutropenia was 10 days.
Neutropenia occurred in 67.3% of patients treated with sacituzumab govitecan, including Grade 3-4neutropenia in 48.6% of patients. Neutropenia was the reason for dose reduction in 14.2% of patients.
Neutropenic colitis was observed in 1.3% of patients. Fatal infections secondary to neutropenia(including neutropenic colitis) occurred in 0.6% of patients.
Febrile neutropenia occurred in 5.6% of patients treated with sacituzumab govitecan. Febrileneutropenia was the reason for dose reduction in 2.7% of patients.
Use in patients with reduced UGT1A1 activity
The incidence of Grade 3-4 neutropenia was 59.6% in patients homozygous for the UGT1A1*28allele, 50.7% in patients heterozygous for the UGT1A1*28 allele, and 44.9% in patients homozygousfor the wild-type allele. The incidence of Grade 3-4 febrile neutropenia was 10.6% in patientshomozygous for the UGT1A1*28 allele, 5.9% in patients heterozygous for the UGT1A1*28 allele,and 4.3% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anaemia was10.6% in patients homozygous for the UGT1A1*28 allele, 6.4% in patients heterozygous for the
UGT1A1*28 allele, and 6.3% in patients homozygous for the wild-type allele. For patientsheterozygous for the UGT1A1*6 allele, the incidences of Grade 3-4 neutropenia, febrile neutropenia,and anaemia were 53.8%, 7.7%, and 7.7%, respectively.
Compared to patients homozygous for the wild-type allele, earlier median onset of neutropenia andanaemia was observed in patients homozygous for the UGT1A1*28 allele and in patients heterozygousfor the UGT1A1*28 allele.
DiarrhoeaThe median time to onset of diarrhoea following the start of the first treatment cycle was 13 days. Themedian duration of diarrhoea was 7 days.
Diarrhoea occurred in 59.9% of patients treated with sacituzumab govitecan. Grade 3 events occurredin 10.0% of patients. Four of 963 patients (< 1%) discontinued treatment because of diarrhoea.
HypersensitivityHypersensitivity reactions reported up to the end of the day following dosing occurred in 12.8% ofpatients treated with sacituzumab govitecan. Grade 3 and above hypersensitivity occurred in 0.5% ofpatients treated with sacituzumab govitecan. The incidence of hypersensitivity reactions leading topermanent discontinuation of sacituzumab govitecan was 0.2%.
ImmunogenicityAcross clinical studies in patients treated with sacituzumab govitecan, 13 (1.2%) of 1058 patientsdeveloped antibodies to sacituzumab govitecan following administration; 10 of these patients (0.9% ofall patients treated with sacituzumab govitecan) had neutralizing antibodies against sacituzumabgovitecan. In study ASCENT-04, no treatment-emergent antibodies against sacituzumab govitecanwere observed in 207 patients who were evaluable for antibodies against sacituzumab govitecan andreceived sacituzumab govitecan 10 mg/kg in combination with pembrolizumab.
Special PopulationsThere was a higher discontinuation rate due to adverse reactions in patients aged 65 years or older(8%) compared with younger patients (4%) with metastatic breast cancer. Higher incidence rates offebrile neutropenia and severe diarrhoea were observed in patients aged 65 years or older. A higherincidence rate of fatal infections was observed in patients aged 65 years or older. There was a higherincidence rate of serious adverse events in patients aged 75 years or older (52%) compared to patientsaged 65 years or older (35%) and patients younger than 65 years (25%) with metastatic breast cancer.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.
4.9 Overdose
In clinical studies, doses of up to 18 mg/kg (approximately 1.8 times the maximum recommendeddose of 10 mg/kg body weight) led to a higher incidence of severe neutropenia.
In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions,in particular severe neutropenia, and appropriate treatment instituted.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antineoplastic agents, monoclonal antibodies and antibody drugconjugates, other monoclonal antibodies, and antibody drug conjugates, ATC code: L01FX17.
Mechanism of actionSacituzumab govitecan binds to Trop-2-expressing tumour cells and is internalised with thesubsequent release of SN-38 from a hydrolysable linker. SN-38 interacts with topoisomerase I andprevents re-ligation of topoisomerase I-induced single strand breaks. The resulting DNA damage leadsto apoptosis and cell death.
Clinical efficacy and safetyTriple Negative Breast Cancer (TNBC)
In Combination with Pembrolizumab in Previously Untreated, Unresectable Locally Advanced or
Metastatic TNBC whose tumours express PD-L1 (ASCENT-04)
The efficacy of sacituzumab govitecan in combination with pembrolizumab was evaluated in amulticentre, open-label, randomised study (ASCENT-04) conducted in 443 patients with unresectablelocally advanced or metastatic TNBC who had not received prior systemic therapy for advanceddisease and whose tumours express PD-L1 (defined using the PD-L1 IHC 22C3 assay as tumours witha CPS ≥ 10) at screening. Patients may have received chemotherapy with or without a PD-1 or PD-L1inhibitor and/or radiotherapy in early-stage TNBC, however at least 6 months must have elapsedbetween the completion of curative systemic breast cancer therapy or surgery, whichever occurred last,and first local or distant recurrence. No prior treatment with topoisomerase 1 inhibitors or antibodydrug conjugates containing a topoisomerase inhibitor was allowed.
Patients with active chronic inflammatory bowel disease or gastrointestinal (GI) perforation within 6months of enrolment or with active serious infections requiring systemic antimicrobial therapy wereexcluded.
Randomisation was stratified by treatment-free interval (de novo versus disease recurrence within 6 to12 months from completion of treatment in the curative setting versus disease recurrence > 12 monthsfrom completion of treatment in the curative setting), and by geographic region (United
State/Canada/Western Europe versus Rest of World), and prior exposure to PD-1 or PD-L1 inhibitor(yes versus no).
Patients were randomised (1:1) to receive either:
* Sacituzumab govitecan 10 mg/kg as an intravenous (IV) infusion on Days 1 and 8 of 21-daycycles and pembrolizumab 200 mg on Day 1 of 21-day cycles. Pembrolizumab wasadministered for a maximum of 35 cycles (approximately 24 months).
* Pembrolizumab 200 mg on Day 1 of 21-day cycles in combination with nab-paclitaxel 100mg/m2 on Days 1, 8 and 15 every 28 days, or paclitaxel 90 mg/m2 on Days 1, 8, and 15 every 28days, or gemcitabine 1000 mg/m2 and carboplatin AUC 2 mg/mL/min on Days 1 and 8 every 21days. Pembrolizumab was administered for a maximum of 35 cycles (approximately 24months).
Patients were treated until blinded independent central review (BICR)-verified disease progression,unacceptable toxicity, death, or consent withdrawal. Tumour imaging was obtained every 8 weeks forthe first 18 months followed by every 12 weeks thereafter. Following BICR-verified radiographicdisease progression and study treatment discontinuation, patients who were randomised to treatment ofphysician’s choice (TPC) and pembrolizumab were able to be enrolled in the crossover phase of thisstudy to receive sacituzumab govitecan monotherapy.
The primary efficacy outcome was progression-free survival (PFS) by BICR per RECIST v1.1.
Additional efficacy outcomes measures included overall survival (OS) and objective response rate(ORR).
The median age of patients in the study population was 55 years (range: 23-88 years), and 26% ofpatients were 65 years or over. All patients were female (100%). The majority of patients were White(58%) and Asian (24%); 6% were American Indian or Alaska Native, 5% were Black, and 3% wereother race. Thirty-four percent of patients presented with de novo metastatic disease at screening, 18%with recurrent disease within 6 to 12 months from completion of treatment in the curative setting and48% with recurrent disease > 12 month from completion of treatment in the curative setting. One-pointfour percent (1.4%) of patients received a prior PD-1 or PD-L1 inhibitor. At study entry, all patientshad an ECOG performance status of 0 (70%) or 1 (30%), 36% of patients were pre-menopausal and64% were post-menopausal. The majority of patients (95%) had metastatic disease at screening, brainmetastases were observed in 3% of patients. BRCA mutation analysis by Whole Exome Sequencingwas available for 75% of participants, of which 21% of the participants had BRCA1 or BRCA2mutated tumours.
Sacituzumab govitecan in combination with pembrolizumab demonstrated a statistically significantimprovement in PFS versus TPC in combination with pembrolizumab as assessed by BICR. At thetime of the interim analysis of OS, patients had a median follow-up of 22.5 months. The efficacyresults are summarized in Table 4, Figure 1 and Figure 2.
Table 4: Efficacy endpoints (ASCENT-04)
Sacituzumab govitecan TPC in10 mg/kg in combination combination withwith Pembrolizumab Pembrolizumabn=221 n=222
Progression-Free Survival by BICR1
Number (%) of patients with events 109 (49%) 140 (63%)
Median PFS in months (95% CI) 11.2 (9.3, 16.7) 7.8 (7.3, 9.3)
Hazard ratio (95% CI)2 0.65 (0.51, 0.84)p-value3 0.0009
Objective Response Rate by BICR1
ORR (95% CI)4 60% (53, 66) 53% (46, 60)
Overall Survival5
Number (%) of patients with events 97 (43.9%) 106 (47.7%)
Median OS in months (95% CI) 31.21 (25.56, NR) 28.39 (24.44, NR)
Hazard ratio (95% CI)2 0.915 (0.694, 1.206)1 Based on PFS primary analysis with median follow-up time 14 months (data cut-off 3 March 2025)2 Hazard ratio based on the stratified Cox proportional hazard model3 Stratified log-rank test adjusted for stratification factors: treatment-free interval (de novo vs recurrent disease within 6 to 12months vs recurrent disease occurring > 12 months from completion of treatment in the curative setting) and geographicregion (US/Canada/Western Europe vs Rest of World4 Based on 2-sided 95% CIs using the Clopper-Pearson method5 Based on interim OS analysis (data cut-off 16 February 2026)
BICR = Blinded Independent Central Review; CI = Confidence Interval
NR= Not reached
TPC = nab-paclitaxel, paclitaxel, or gemcitabine
Figure 1: Progression free survival by BICR in ASCENT-04
Figure 2: Overall survival in ASCENT-04
Previously Untreated, Unresectable Locally Advanced or Metastatic TNBC in patients who are notcandidates for PD-1/PD-L1 inhibitor therapy (ASCENT-03)
The efficacy of sacituzumab govitecan was evaluated in a multicentre, open-label, randomised study(ASCENT-03) conducted in 558 patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who had not received previous systemic therapy for advanceddisease and who were not candidates for PD-1 or PD-L1 inhibitor therapy. The study enrolled patientswith tumours that are PD-L1 negative (defined as having a tumour CPS < 10 using the IHC 22C3assay), and patients with tumours that are PD-L1 positive (defined as having a CPS ≥ 10 using the IHC22C3 assay) if they received a PD-1 or PD-L1 inhibitor in the (neo)adjuvant setting or if they had acomorbidity precluding treatment with PD-1 or PD-L1 inhibitor therapy.
Patients may have received chemotherapy with or without a PD-1 or PD-L1 inhibitor and/orradiotherapy in the early-stage of TNBC, however at least 6 months must have elapsed between thecompletion of systemic (neo) adjuvant breast cancer therapy or surgery, whichever occurred last, andfirst local or distant recurrence. No prior treatment with topoisomerase 1 inhibitors or antibody drugconjugates containing a topoisomerase inhibitor was allowed.
Patients were randomised (1:1) to receive sacituzumab govitecan 10 mg/kg as an intravenous infusionon Days 1 and 8 of a 21-day cycle (n=279) or Treatment of Physician’s Choice (TPC) (n=279). TPCwas determined by the investigator before randomisation from one of the following regimens:gemcitabine and carboplatin, paclitaxel or nab-paclitaxel. Randomisation was stratified by de novo vsrecurrent disease within 6 to 12 months from completion of treatment in the curative setting versusrecurrent disease > 12 months from completion of treatment in the curative setting, and by geographicregion (United States, Canada, Western Europe vs. Rest of World).
Patients were treated until BICR-verified disease progression, unacceptable toxicity, death, or consentwithdrawal. Tumour imaging was obtained every 6 weeks for the first year followed by every12 weeks thereafter. Following BICR-verified objective disease progression and study treatmentdiscontinuation, patients who were randomised to TPC chemotherapy were able to receivesacituzumab govitecan supplied on trial in the crossover phase of this study if eligible.
The primary efficacy outcome was progression-free survival (PFS) by BICR per RECIST v1.1.
Additional efficacy outcomes measures included overall survival (OS) and objective response rate(ORR) by BICR.
The median age of the study population was 55 years (range: 23-86 years), and 26% of patients were65 years or over; 99.5% of patients were female. The majority of patients were White (64%); 23%were Asian, 3% were Black, and 4% were other race. Thirty-one percent (31%) of patients had denovo disease, 21% of patients had recurrent disease with a disease-free interval (DFI) 6 to 12 monthsand 48% of patients with DFI > 12 months. Ninety-nine point five percent (99.5%) of patients enrolledhad tumours that were PD-L1 negative and 0.5% of patients had tumours that were PD-L1 positive. Atstudy entry, all patients had an ECOG performance status of 0 (66%) or 1 (34%). The majority ofpatients (97.8%) had metastatic disease at screening; brain metastases were observed in 5% ofpatients. BRCA 1/2 mutation status was known for 76% of participants, out of which 18% of testedstudy participants had positive BRCA mutations.
Sacituzumab govitecan demonstrated a statistically significant improvement in PFS versus TPC by
BICR. At the time of the first interim OS analysis, patients had a median follow-up of 17.7 months.
Efficacy results are summarized in Table 5, Figure 3 and Figure 4.
Table 5. Efficacy endpoints (ASCENT-03)
Sacituzumab govitecan TPC
N=279 N=279
Progression-free survival by BICR1
Number (%) of patients with events 161 (58%) 188 (67%)
Median PFS in months (95% CI) 9.7 6.9(8.1, 11.1) (5.6, 8.2)
Hazard ratio (95% CI)2 0.62 (0.50, 0.77)p-value3 < 0.0001
Objective response rate by BICR1
ORR, (95% CI)4 48% 46%(42%, 54%) (40%, 52%)
Overall survival5
Sacituzumab govitecan TPC
N=279 N=279
Number (%) of patients with events 139 (50%) 144 (52%)
Median OS in months (95% CI) 21.5 (18.9, 26.5) 21.3 (18.7, 25.2)
Hazard ratio (95% CI)2 0.95 (0.75, 1.20)1. Based on PFS primary analysis (data cut-off 2 April 2025) with median follow-up time 13.2 months.2. Hazard ratio with 95% CIs based on the stratified Cox proportional hazards model adjusted for randomisationstratification factors: disease stratification (de novo vs recurrent disease within 6 to 12 months vs recurrent diseaseoccurring > 12 months from completion of treatment in the curative setting) and geographic region(US/Canada/Western Europe vs rest of the world).
3. 2-sided p-value based on log-rank test adjusted for randomisation stratification factors: disease stratification (de novovs recurrent disease within 6 to 12 months vs recurrent disease occurring > 12 months from completion oftreatment in the curative setting) and geographic region (US/Canada/Western Europe vs rest of the world)4. The 95% CI is based on the Clopper-Pearson exact method.5. Based on first interim OS analysis (data cut-off 27 October 2025) with median follow-up time 17.7 months
BICR = Blinded Independent Central Review; CI = Confidence Interval
TPC = gemcitabine and carboplatin, paclitaxel, or nab-paclitaxel
Figure 3: Progression free survival by BICR in ASCENT-03 (data cut-off date 2 April 2025)
Trodelvy
TPC
Censored
Time (months)
Number of Patients at Risk
Trodelvy
TPC
Probability of PFS (%)
Figure 4: Overall survival in ASCENT-03 (data cut-off date 27 Oct 2025)
Trodelvy
TPC
Censored
Time (months)
Number of Patients at Risk
Trodelvy
TPC
Unresectable or metastatic Triple Negative Breast Cancer (ASCENT)
The efficacy and safety of sacituzumab govitecan was assessed in ASCENT (IMMU-132-05), aninternational Phase 3, multicentre, open-label, randomised study conducted in 529 patients withunresectable locally advanced or metastatic TNBC who had relapsed after at least two priorchemotherapies (no upper limit) for breast cancer. Earlier adjuvant or neoadjuvant therapy for morelimited disease qualified as one of the required prior regimens if the development of unresectable,locally advanced or metastatic disease occurred within a 12-month period of time after completion ofchemotherapy. All patients received previous taxane treatment in either the adjuvant, neoadjuvant, oradvanced stage unless they had a contraindication or were intolerant to taxanes. Poly-ADP ribosepolymerase (PARP) inhibitors were allowed as one of the two prior chemotherapies for patients with adocumented germline BRCA1/BRCA2 mutation.
Patients were randomised (1:1) to receive sacituzumab govitecan 10 mg/kg as an intravenous infusionon Day 1 and Day 8 of a 21-day treatment cycle or TPC which was dosed based on body surface areaand per the approved product information. TPC was determined by the investigator beforerandomisation from one of the following single-agent regimens: eribulin (n = 139), capecitabine(n = 33), gemcitabine (n = 38), or vinorelbine (except if patient had ≥ Grade 2 neuropathy, n = 52).
Patients with stable brain metastases (pre-treated, non-progressive, without anti-seizure medicinalproducts and on stable corticosteroid dose for at least 2 weeks) were eligible. Magnetic resonanceimaging (MRI) to determine brain metastases was required only for patients with known or suspectedbrain metastases. Patients with known Gilbert’s disease, bone-only disease, known history of unstableangina, myocardial infarction, or congestive heart failure, active chronic inflammatory bowel diseaseor gastrointestinal (GI) perforation, human immunodeficiency virus (HIV), active hepatitis B or Cinfection, live vaccine within 30 days, or who have previously received irinotecan were excluded.
Patients were treated until disease progression or unacceptable toxicity. The primary efficacy endpointwas PFS in patients without brain metastases at baseline (i.e. BMNeg) as measured by a BICR groupof radiology experts using RECIST v1.1 criteria. Secondary efficacy endpoints included PFS by BICRfor the overall population, including all patients with and without brain metastases, overall survival(OS), objective response rate (ORR) and duration of response (DOR).
The primary analysis included 235 BMNeg patients in the sacituzumab govitecan group and233 BMNeg patients in the TPC group. The analysis of the overall population included 267 patients inthe sacituzumab govitecan group and 262 patients in the TPC group.
The demographics and baseline characteristics of the overall population (n = 529) were: median age of54 years (range: 27-82 years) and 81% < 65 years; 99.6% female; 79% White; 12% Black; mediannumber of prior systemic therapies was 4; 69% had previously received 2 to 3 prior chemotherapies;31% had previously received > 3 prior chemotherapies; 42% had hepatic metastases; 12% had presentor a history of brain metastases. 8% were BRCA1/BRCA2 mutational status positive; BRCA statuswas available for 339 patients. At study entry, all patients had an ECOG performance status of 0(43%) or 1 (57%). The median time from diagnosis of Stage 4 to study entry was 16.2 months (range:
- 0.4 to 202.9 months). The most frequent prior chemotherapies were cyclophosphamide (83%),anthracycline (83%) including doxorubicin (53%), paclitaxel (78%), carboplatin (65%), capecitabine(67%), gemcitabine (36%), docetaxel (35%), and eribulin (33%). Overall, 29% of patients hadreceived prior PD-1 or PD-L1 therapy. Thirteen percent of patients in the sacituzumab govitecan groupin the overall population received only 1 prior line of systemic therapy in the metastatic setting.
The efficacy results in the BMNeg population showed a statistically significant improvement ofsacituzumab govitecan over TPC in PFS and OS with hazard ratios (HR) of 0.41 (n=468; 95% CI:0.32, 0.52; p-value: <0.0001) and 0.48 (n=468; 95% CI: 0.38, 0.59; p-value: <0.0001), respectively.
The median PFS was 5.6 months vs 1.7 months; the median OS was 12.1 months vs 6.7 months, inpatients treated with sacituzumab govitecan and TPC, respectively.
The efficacy results in the overall population were consistent with the BMNeg population in the pre-specified final analysis (11 March 2020 cut-off date) and are summarised in Table 6.
Table 6: Efficacy endpoints (overall population) - pre-specified final analysis (ASCENT)
Pre-specified Final Analysis(11 March 2020 cut-off date)
Sacituzumab govitecan Treatment of physician’sn=267 choice (TPC)n=262
Progression-free survival1
Number of events (%) 190 (71.2) 171 (65.3)
Median PFS in months (95% CI) 4.8 1.7(4.1,5.8) (1.5, 2.5)
Hazard ratio (95% CI) 0.43 (0.35, 0.54)p-value2 <0.0001
Overall survival
Number of deaths (%) 179 (67.0) 206 (78.6)
Median OS in months (95% CI) 11.8 6.9(10.5, 13.8) (5.9, 7.7)
Hazard ratio (95% CI) 0.51 (0.41, 0.62)p-value2 <0.0001
Overall response rate (ORR)
Number of responders (%) 83 (31) 11 (4)
Odds ratio (95% CI) 10.99 (5.66, 21.36)p-value3 <0.0001
Complete response, n (%) 10 (4) 2 (1)
Partial response, n (%) 73 (27) 9 (3)
Duration of response (DOR)
Median DOR in months 6.3 3.6(95% CI) (5.5, 9.0) (2.8, NE)1 PFS is defined as the time from the date of randomization to the date of the first radiological disease progressionor death due to any cause, whichever comes first.2 Stratified log-rank test adjusted for stratification factors: number of prior chemotherapies, presence of knownbrain metastases at study entry, and region.3 Based on Cochran-Mantel-Haenszel test.
CI = Confidence Interval
In an updated efficacy analysis (final database lock 25 February 2021), results were consistent with thepre-specified final analysis. The median PFS by BICR was 4.8 months vs 1.7 months, in patientstreated with sacituzumab govitecan and TPC, respectively (HR of 0.41; 95% CI: 0.33, 0.52). Themedian OS was 11.8 months vs 6.9 months, respectively (HR of 0.51; 95% CI: 0.42, 0.63). Kaplan-
Meier curves for updated PFS by BICR and OS are presented in Figures 5 and 6.
Figure 5: Progression free survival (overall population; final database lock 25 February 2021)by BICR in ASCENT
Trodelvy
TPC
Censored
Time (months)
Number of Patients at Risk
Trodelvy 267 184 135 82 55 34 23 17 11 8 5 1 0
TPC 262 86 36 12 6 3 1 1 0 0 0 0 0
Figure 6: Overall survival (overall population; final database lock 25 February 2021) in
ASCENT
Trodelvy
TPC
Censored
Time (months)
Number of Patients at Risk
Trodelvy 267 250 232 209 178 152 125 108 79 62 49 37 25 14 7 2 0
TPC 262 222 174 132 101 66 54 45 34 31 26 12 7 3 2 0 0
Probability of OS (%) Probability of PFS (%)
Sub-group analysis
In subgroup analyses, improvements in PFS and OS in patients treated with sacituzumab govitecancompared to TPC were consistent across patient subgroups irrespective of age, race, BRCA status,prior number of systemic therapies overall (2 and >2, 2-3 and >3) and in the metastatic setting (1 and>1), prior therapy with anthracycline or PDL1, and liver metastases.
Brain metastases
An exploratory analysis of PFS and OS in patients with previously treated, stable brain metastasesshowed a stratified HR of 0.65 (n=61; 95% CI: 0.35, 1.22) and 0.87 (n=61; 95% CI: 0.47, 1.63),respectively. The median PFS was 2.8 months vs 1.6 months; the median OS was 6.8 months vs 7.5months, in patients treated with sacituzumab govitecan and TPC, respectively.
Trop-2 expression
Additional subgroup analyses were conducted to evaluate the efficacy by tumour Trop-2 expressionlevels and the results were consistent across the different scoring methods used. In patients with low
Trop-2 levels using membrane H-score by quartiles, benefit of sacituzumab govitecan over TPC wasshown for both PFS (HR 0.64; 95% CI: 0.37, 1.11) and OS (HR of 0.71; 95% CI: 0.42, 1.21).
HR-Positive, HER2-Negative Breast Cancer
Unresectable or metastatic HR-positive/ HER2-negative breast cancer (TROPiCS-02)
The efficacy of sacituzumab govitecan was evaluated in a multicentre, open-label, randomised study
TROPiCS-02 (IMMU-132-09) conducted in 543 patients with unresectable locally advanced ormetastatic HR-positive, HER2-negative (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer whose diseasehas progressed after the following in any setting: a CDK 4/6 inhibitor, endocrine therapy, and ataxane; patients received at least two prior chemotherapies in the metastatic setting (one of whichcould be in the neoadjuvant or adjuvant setting if progression or recurrence occurred within 12 monthsof completion of the chemotherapy). Patients with bone-only disease, active chronic inflammatorybowel disease and known history of bowel obstruction, known history of unstable angina ormyocardial infarction or congestive heart failure or active hepatitis B or C infection were excludedfrom the study.
Patients were randomised (1:1) to receive sacituzumab govitecan 10 mg/kg as an intravenous infusionon Days 1 and 8 of a 21-day cycle (n=272) or TPC (n=271). TPC was determined by the investigatorbefore randomisation from one of the following single-agent regimens: eribulin (n=130), vinorelbine(n=63), gemcitabine (n=56), or capecitabine (n=22). Randomisation was stratified based on priorchemotherapy regimens for metastatic disease (2 vs. 3-4), visceral metastasis (yes vs. no), andendocrine therapy in the metastatic setting for at least 6 months (yes vs. no).
Patients were treated until disease progression or unacceptable toxicity. The primary efficacy outcomemeasure was PFS as determined by BICR per RECIST v1.1. Additional efficacy outcome measureswere OS, ORR by BICR, and DOR by BICR.
The median age of the study population was 56 years (range: 27-86 years), and 26% of patients were65 years or over. Almost all patients were female (99%). The majority of patients were White (67%);4% were Black, 3% were Asian, and 26% were of unknown race. Patients received a median of 7(range: 3 to 17) prior systemic regimens in any setting and 3 (range: 0 to 8) prior systemicchemotherapy regimens in the metastatic setting. Approximately 42% of patients had 2 priorchemotherapy regimens for metastatic disease compared to 58% of patients who had 3 to 4 priorchemotherapy regimens. Most patients received endocrine therapy in the metastatic setting for ≥ 6months (86%). Patients had an ECOG performance status of 0 (44%) or 1 (56%). Ninety-five percentof patients had visceral metastases; 4.6% of patients had stable, pre-treated brain metastases.
Sacituzumab govitecan demonstrated a statistically significant improvement in PFS by BICR and OSversus TPC. The improvement in PFS by BICR and OS was generally consistent across pre-specifiedsubgroups. Efficacy results are summarized in Table 7.
Table 7. Efficacy endpoints - Pre-specified final analysis (TROPiCS-02)
Sacituzumab govitecan TPCn=272 n=271
Progression-free survival by BICR1
Number of events (%) 170 (62.5%) 159 (58.7%)
Median PFS in months (95% CI) 5.5 (4.2, 7.0) 4.0 (3.1, pct. 4.4)
Hazard ratio (95% CI) 0.661 (0.529, 0.826)p-value2 0.0003
PFS rate at 12 months, % (95% 21.3 (15.2, 28.1) 7.1 (2.8, 13.9)
CI)
Overall survival3
Number of events (%) 191 (70.2%) 199 (73.4%)
Median OS in months (95% CI) 14.4 (13.0, 15.7) 11.2 (10.1, 12.7)
Hazard ratio (95% CI) 0.789 (0.646, 0.964)p-value2 0.0200
Objective response rate by BICR3
Number of responders (%) 57 (21.0%) 38 (14.0%)
Odds ratio (95% CI) 1.625 (1.034, 2.555)p-value 0.03481 PFS is defined as the time from the date of randomisation to the date of the first radiological disease progression or deathdue to any cause, whichever comes first (data cut-off 3 January 2022).2 Stratified log-rank test adjusted for stratification factors: prior chemotherapy regimens for metastatic disease (2 vs. 3-4),visceral metastasis (yes vs. no), and endocrine therapy in the metastatic setting for at least 6 months (yes vs. no).3 Based on second interim OS analysis (data cut-off 1 July 2022).
BICR = Blinded Independent Central Review; CI = Confidence Interval
In an updated efficacy analysis with a median duration of follow-up of 12.8 months (data cut-off 1
December 2022), results were consistent with the pre-specified final analysis. The median PFS by
BICR was 5.5 months vs 4.0 months, in patients treated with sacituzumab govitecan and TPC,respectively (HR of 0.65; 95% CI: 0.53, 0.81). The median OS was 14.5 months vs 11.2 months,respectively (HR of 0.79; 95% CI: 0.65, 0.95). Kaplan-Meier curves for updated PFS by BICR and OSare presented in Figures 7 and 8.
Figure 7: Progression free survival by BICR (data cut-off 1 December 2022) in TROPiCS-02
Figure 8: Overall Survival (data cut-off 1 December 2022) in TROPiCS-02
Paediatric populationThe European Medicines Agency has waived the obligation to submit the results of studies withsacituzumab govitecan in all subsets of the paediatric population for the treatment of breast cancer (seesection 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
The serum pharmacokinetics of sacituzumab govitecan and SN-38 were evaluated in patients withmetastatic breast cancer (mBC) who received sacituzumab govitecan at a dose of 10 mg/kg asmonotherapy or in combination with pembrolizumab. The pharmacokinetic parameters of sacituzumabgovitecan and free SN-38 when administered as monotherapy or in combination with pembrolizumabare presented in Table 8.
There was no impact of pembrolizumab coadministration on pharmacokinetics of sacituzumabgovitecan or SN-38.
Table 8: Summary of mean PK parameters (CV%) of sacituzumab govitecan and free SN-38
Sacituzumab govitecan Free SN-38
Cmax [ng/mL] 258378 (17%) 97 (41%)
AUC0-168 [ng*h/mL] 12285980 (19%) 3120 (62%)
*Parameters estimated based on population PK analyses
Cmax: maximum serum concentration from 0-168 hours after the first dose
AUC0-168: area under serum concentration curve through 168 hours after the first dose
DistributionBased on population pharmacokinetic analyses, the steady state volume of distribution of sacituzumabgovitecan when administered as monotherapy or in combination with pembrolizumab was 4.79 L.
BiotransformationNo metabolism studies with sacituzumab govitecan have been conducted.
SN-38 (the small molecule moiety of sacituzumab govitecan) is metabolised via UGT1A1.
EliminationThe median elimination half-life (t1/2) of sacituzumab govitecan and free SN-38, based on populationpharmacokinetic analysis, in patients who received sacituzumab govitecan as monotherapy or incombination with pembrolizumab, was 170 and 21.4 hours, respectively. The estimated mean (%CV)clearance of sacituzumab govitecan is 0.129 L/h (21%).
Special populationsPharmacokinetic analyses in patients treated with sacituzumab govitecan did not identify an effect ofage, race, and mild or moderate renal impairment on the pharmacokinetics of sacituzumab govitecan.
Renal impairmentRenal elimination is known to contribute minimally to the excretion of SN-38, the small moleculemoiety of sacituzumab govitecan. There are no data on the pharmacokinetics of sacituzumab govitecanin patients with severe renal impairment or end-stage renal disease (CrCl < 15 mL/min).
Hepatic Impairment
The exposure of sacituzumab govitecan is similar in patients with mild hepatic impairment (bilirubin≤ ULN and AST > ULN, or bilirubin > 1.0 to ≤ 1.5 ULN and AST of any level;) to patients withnormal hepatic function (bilirubin and AST ≤ ULN;).
There is limited data on sacituzumab govitecan and free SN-38 exposures in patients with moderate orsevere hepatic impairment.
5.3 Preclinical safety data
SN-38 was clastogenic in an in vitro mammalian cell micronucleus test in Chinese hamster ovary cellsand was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay.
In a repeat-dose toxicity study in cynomolgus monkeys, intravenous administration of sacituzumabgovitecan resulted in endometrial atrophy, uterine hemorrhage, increased follicular atresia of theovary, and atrophy of vaginal epithelial cells at doses ≥ 60 mg/kg (1.9 times the human recommendeddose of 10 mg/kg based on body weight allometric scaling).
Non-clinical data for the novel excipient MES reveal no special hazard for humans based onconventional repeated dose toxicity and genotoxicity studies.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
2-(N-morpholino)ethane sulfonic acid (MES)
Polysorbate 80 (E433)
Trehalose dihydrate
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned insection 6.6.
6.3 Shelf life
Unopened vial3 years.
After reconstitutionThe reconstituted solution should be used immediately to prepare the diluted solution for infusion. Ifnot used immediately, the infusion bag containing diluted solution can be stored in a refrigerator (2°Cto 8°C) for up to 24 hours protected from light.
6.4 Special precautions for storage
Store in a refrigerator (2°C - 8°C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.
6.5 Nature and contents of container
Type I colourless, clear glass 50 mL vial, with an elastomeric butyl stopper and sealed with analuminum flip-off overseal containing 200 mg of sacituzumab govitecan.
Each pack contains one vial.
6.6 Special precautions for disposal and other handling
Trodelvy is a cytotoxic medicinal product. Applicable special handling and disposal procedures haveto be followed.
Reconstitution* Calculate the required dose (mg) of Trodelvy based on the patient’s body weight.
* Using a sterile syringe, slowly inject 20 mL of sodium chloride 9 mg/mL (0.9%) solution forinjection into each vial. The resulting concentration will be 10 mg/mL.
* Gently swirl vials and allow to dissolve for up to 15 minutes. Do not shake. The product shouldbe inspected visually for particulate matter and discoloration prior to administration. Thesolution should be free of visible particulates, clear and yellow. Do not use the reconstitutedsolution if it is cloudy or discoloured.
* Use immediately to prepare a diluted solution for infusion.
Dilution* Calculate the required volume of the reconstituted solution needed to obtain the appropriatedose according to the patient’s body weight.
* Determine the final volume of the infusion solution to deliver the appropriate dose at asacituzumab govitecan concentration range of 1.1 mg/mL to 3.4 mg/mL.
* Withdraw and discard a volume of sodium chloride 9 mg/mL (0.9%) solution for injection fromthe final infusion bag that is equivalent to the required volume of the reconstituted solution.
* Withdraw the calculated amount of the reconstituted solution from the vial(s) using a syringe.
Discard any unused portion remaining in the vial(s).
* To minimize foaming, slowly inject the required volume of reconstituted solution into apolyvinyl chloride, polyolefin (polypropylene and/or polyethylene) or ethylene vinyl acetateinfusion bag. Do not shake the contents.
* If necessary, adjust the volume in the infusion bag as needed with sodium chloride 9 mg/mL(0.9%) solution for injection, to obtain a concentration of 1.1 mg/mL to 3.4 mg/mL. Onlysodium chloride 9 mg/mL (0.9%) solution for injection should be used since the stability of thereconstituted product has not been determined with other infusion-based solutions.
* If not used immediately, the infusion bag containing diluted solution can be stored refrigerated2°C to 8°C for up to 24 hours protected from light. Do not freeze. After refrigeration, administerthe diluted solution at room temperature up to 25°C within 8 hours (including infusion time).
Administration* Administer Trodelvy as an intravenous infusion. Protect the infusion bag from light. Theinfusion bag should be covered during administration to the subject until dosing is complete. Itis not necessary to cover the infusion tubing or to use light-protective tubing during the infusion.
* An infusion pump may be used.
* Do not mix Trodelvy, or administer as an infusion, with other medicinal products.
* Upon completion of the infusion, flush the intravenous line with 20 mL sodium chloride9 mg/mL (0.9%) solution for injection.
DisposalAny unused medicinal product or waste material should be disposed of in accordance with localrequirements.
10. DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is available on the website of the European Medicines
Agency http://www.ema.europa.eu.