A Randomized Open-Label Phase III Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Subjects With Metastatic or Locally Advanced Unresectable Urothelial Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Jun 2021 → 4 Jul 2025

Decision date (initial)

2024-10-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Gilead Sciences, Inc.

External identifiers

EU CT number

2024-513870-23-00

EudraCT number

2020-002964-29

ClinicalTrials.gov

NCT04527991

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Therapy, Safety, Pharmacoeconomic, Efficacy, Pharmacogenetic

To assess overall survival (OS) with sacituzumab govitecan in comparison with treatment of physician’s choice (TPC) in subjects with metastatic or locally advanced unresectable urothelial cancer (UC)

Secondary objectives 4

1. To assess progression-free survival (PFS) of sacituzumab govitecan in comparison with TPC by investigator assessment and blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
2. To assess objective response rate (ORR), clinical benefit rate (CBR), and duration of objective tumor response (DOR) with sacituzumab govitecan in comparison with TPC by investigator assessment and BICR using RECIST v1.1
3. To assess safety and tolerability of sacituzumab govitecan in comparison with TPC
4. To assess Quality of Life (QOL) based on European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) with sacituzumab govitecan in comparison with TPC

Conditions and MedDRA coding

Locally Advanced or Metastatic Unresectable Urothelial Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Subjects meeting all of the following inclusion criteria at Screening/Baseline will be eligible for participation in the study: Female or male subjects, ≥18 years of age, able to understand and give written informed consent.
2. Subjects with histologically documented UC that is metastatic or locally advanced unresectable defined as Tumor (T) 4b, any node (N) or Any T, N 2-3
3. Tumors of upper and lower urinary tract are permitted. Mixed histologic types are allowed if urothelial is the predominant histology.
4. ECOG performance status (PS) score of 0 or 1.
5. Subjects with progression or recurrence following receipt of platinum-containing regimen and anti-PD-1/PD-L1 therapy for metastatic or locally advanced unresectable disease will be enrolled. a) Subjects with recurrence or progression ≤12 months following completion of cisplatincontaining chemotherapy given in the neo-adjuvant/adjuvant setting may utilize that line of therapy to be eligible for the study. The 12-month period is counted from completion of surgical intervention or cisplatin therapy, respectively. These subjects must receive anti-PD-1/PD L1 therapy in the metastatic or locally advanced unresectable setting to be eligible. b) Subjects who received either carboplatin or anti-PD-1/PD-L1 therapy in the neoadjuvant/ adjuvant setting will not be able to count that line of therapy towards eligibility for the study. c) Cisplatin-ineligible subjects who meet one of the below criteria and who were treated with carboplatin in the metastatic or locally advanced unresectable settings may count that line of therapy towards eligibility. They must then have received anti-PD-1/PD-L1 therapy in metastatic or locally advanced unresectable setting to be eligible for the study. Cisplatin ineligibility is defined as meeting one of the following criteria: i) Creatinine Clearance <60 mL/min ii) Grade ≥2 Audiometric Hearing Loss iii) Grade ≥2 Peripheral Neuropathy iv) New York Heart Association (NYHA) Class III heart failure v) ECOG PS ≥2 d) Anti-PD-1/PD-L1 therapy administered as part of maintenance therapy may be counted towards eligibility for the study e) Subjects who have progressed after receiving enfortumab vedotin in prior lines of therapy, and subjects who are either ineligible or unable to tolerate enfortumab vedotin therapy, are eligible to enroll in the study. f) Subjects who received only concurrent chemoradiation for bladder preservation without further systemic therapy are not eligible to enroll in the study. The substitution of carboplatin for cisplatin does not constitute a new regimen provided no new chemotherapeutic agents were added to the regimen and no progression was noted prior to the change in platinum.
6. Subjects with previously treated brain metastases may participate in the study provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and stabilization of all neurologic symptoms, have no evidence of new or enlarging brain metastases, and are not using steroids >20 mg of prednisone (or equivalent) daily for brain metastases for at least 7 days prior to first dose of the study drug.
7. Adequate hematologic counts without transfusion or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥9 g/dL, absolute neutrophil count [ANC] ≥1,500/mm3, and platelets ≥100,000/μL).
8. Adequate hepatic function (bilirubin ≤1.5 x institutional upper limit of normal [IULN], aspartate aminotransferase [AST] and alanine aminotransferase [ALT] ≤2.5 x IULN or ≤5 x IULN if known liver metastases and serum albumin ≥3 g/dL). Docetaxel will only be option in TPC arm for subjects with a total bilirubin ≤1 x IULN, and an AST and/or ALT ≤1.5 x IULN if alkaline phosphatase is also >2.5 x IULN.
9. Creatinine clearance ≥30 mL/min as assessed by the Cockcroft-Gault equation or other validated instruments (eg Modification of Diet in Renal Disease [MDRD] equation).
10. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix 6 of the protocol

Exclusion criteria 15

1. Subjects meeting any of the following exclusion criteria at Screening/Baseline will not be enrolled in the study: Women who are pregnant or lactating (see Appendix 6).
2. Have had a prior anti-cancer mAb/ADC within 4 weeks prior to C1D1 or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to C1D1. Subjects participating in observational studies are eligible.
3. Have received prior chemotherapy for UC with any available SOC therapies in the control arm (ie, either prior paclitaxel and docetaxel in countries where vinflunine is not an approved therapy, or either prior paclitaxel, docetaxel and vinflunine in countries where vinflunine is approved and is commercially available).
4. Have not recovered (ie, ≤Grade 1) from AEs due to previously administered chemotherapeutic agent. Note: Subjects with ≤Grade 2 neuropathy or any grade of alopecia are an exception to this criterion and will qualify for the study. Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study therapy.
5. Have previously received topoisomerase 1 inhibitors.
6. Have an active second malignancy. Note: Subjects with a history of malignancy that have been completely treated and with no evidence of active cancer for 3 years prior to enrollment, or subjects with surgically cured tumors with low risk of recurrence are allowed to enroll in the study after discussion with the medical monitor
7. Have active cardiac disease, defined as: a) Myocardial infarction or unstable angina pectoris within 6 months of C1D1. b) History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation. c) NYHA Class III or greater congestive heart failure or left ventricular ejection fraction of <40%.
8. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or gastrointestinal (GI) perforation within 6 months of enrollment.
9. Have an active serious infection requiring anti-infective therapy (Contact medical monitor for clarification).
10. Have uncontrolled HIV-1/2 viral load (ie, ≥ 200 copies/mL and/or CD4+ count < 350 cells/mm3) and/or on medications that may interfere with SN-38 metabolism.
11. Have active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). In subjects with a history of HBV or HCV, subjects with a detectable viral load will be excluded.
12. Have other concurrent medical or psychiatric conditions that, in the investigator’s opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
13. Have inability to tolerate or are allergic to any potential TPC agent or sacituzumab govitecan or unable or unwilling to receive the doses specified in the protocol.
14. Have inability to complete all specified study procedures for any reason.
15. History of active interstitial lung disease or noninfectious pneumonitis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. OS

Secondary endpoints 4

1. PFS by investigator assessment and BICR using RECIST v1.1
2. ORR, CBR and DOR by investigator assessment and BICR using RECIST v1.1
3. Safety and tolerability evaluated by AEs, SAEs, and laboratory changes
4. Change from baseline in the physical functioning, global health status, pain, and fatigue scales of the EORTC QLQ-C30 score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 8

Locations

8 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 79 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications