A Study of Sacituzumab Govitecan (IMMU-132) in Subjects with Metastatic Solid Tumors

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

29 Jul 2022 → ongoing

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences Inc

External identifiers

EU CT number

2024-513611-28-00

EudraCT number

2019-000579-18

ClinicalTrials.gov

NCT03964727

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

Assess the ORR of sacituzumab govitecan in subjects with metastatic solid tumors by Investigator's assessment according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria.

Secondary objectives 5

1. Assess the ORR, duration of response (DOR), clinical benefit rate (CBR), and progression-free survival (PFS) of sacituzumab govitecan in subjects with metastatic solid tumors by blinded independent central review (BICR) according to RECIST 1.1 criteria.
2. Assess the DOR, CBR, and PFS of sacituzumab govitecan in subjects with metastatic solid tumors by Investigator's assessment according to RECIST 1.1 criteria.
3. Assess the OS of sacituzumab govitecan in subjects with metastatic solid tumors.
4. Assess the safety of sacituzumab govitecan in subjects with metastatic solid tumors.
5. Assess the PK and immunogenicity of sacituzumab govitecan in subjects with metastatic solid tumors

Conditions and MedDRA coding

Metastatic Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Subjects meeting all the following inclusion criteria at Screening will be eligible for participation in the study. Female or male subjects, > 18 years of age, who are able to understand and give written informed consent.
2. Subjects with the following histologically documented metastatic (M1, Stage IV) or locally advanced solid tumors. 2.1 NSCLC (adenocarcinoma or SCC) that has progressed after prior platinum-based chemotherapy and programmed death-(ligand) 1 (PD- (L)1) directed therapy given sequentially (in either order) or in combination. These agents could have been taken as monotherapy or in combination with other agents. If subjects have had recurrence/relapse or lack of response within 6 months of completing chemotherapy with or without PD-(L)1 directed therapy for locally advanced disease, that line of therapy may be counted for eligibility. 2.2 HNSCC that has progressed after prior platinum-based chemotherapy and anti-PD-(L)1 directed therapy given sequentially (in either order) or in combination. These agents could have been taken as monotherapy or in combination with other agents. No more than 3 prior lines of systemic treatment is allowed. 2.3 Endometrial carcinoma that has progressed after prior platinum-based chemotherapy and anti- PD-(L)1 directed therapy given sequentially (in either order) or in combination. These agents could have been taken as monotherapy or in combination with other agents. No more than 3 prior lines of systemic treatment is allowed. Endometrial carcinoma with any histology including microsatellite instability-high /mismatch repair deficient and microsatellite stable (MSI-h/dMMR and MSS) are allowed. 2.4 Extensive stage SCLC that has progressed after prior platinum-based chemotherapy and PD-(L)1 directed therapy. No more than one prior line of systemic treatment is allowed (re-challenge with the same initial regimen is not allowed).
3. ECOG Performance Status score of 0 or 1.
4. Adequate hematologic counts without transfusional 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).
5. Adequate hepatic function (bilirubin ≤ 1.5 institutional upper limit of normal [IULN], aspartate aminotransferase [AST], and alanine aminotransferase [ALT] ≤ 2.5 × IULN or ≤ 5 × IULN if known liver metastases and serum albumin > 3 g/dL).
6. Creatinine clearance ≥ 30 mL/min as assessed by Cockcroft-Gault.
7. Subjects must have at least a 3-month life expectancy.
8. Have measurable disease by CT or MRI scan as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area may be utilized if they are considered measurable and PD has been demonstrated in such lesions
9. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
10. Tumor blocks (preferably obtained within 12 months of study entry if clinically feasible) or 20 newly sectioned unstained slides (6 slides minimum) of archived biopsy/surgical specimens are requested. A baseline biopsy is required if archival tissue is not available. Fine needle aspirates and bone biopsies are not suitable samples. These specimens should be submitted within the 28-day screening period, after the subject provides written informed consent.

Exclusion criteria 15

1. Subjects meeting any of the following exclusion criteria at Screening will not be enrolled in the study. Positive serum pregnancy test (Appendix 17.5) or women who are lactating.
2. Are currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to the first dose of study drug. Subjects participating in observational studies are eligible.
3. Have had a prior anti-cancer biologic agent within 4 weeks prior to study Day 1 or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1.
4. Have not recovered (ie, ≤ Grade 1) from AEs due to a previously administered agent.
5. Have previously received topoisomerase I inhibitors (for SCLC cohort: Etoposide with platinum combination in first-line setting is allowed).
6. Have an active second malignancy.
7. Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all neurologic symptoms have returned to baseline, no evidence of new or enlarging brain metastases and are taking ≤ 20 mg/day of prednisone or its equivalent. All subjects with carcinomatous meningitis are excluded regardless of clinical stability.
8. Have active cardiac disease, defined as: 8.1 Myocardial infarction or unstable angina pectoris within 6 months of Day 1. 8.2 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 anti-arrhythmic medication); history of QT interval prolongation. 8.3 New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of < 40%.
9. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease), immune-mediated colitis, or gastrointestinal (GI) perforation within 6 months of C1D1.
10. Have an active infection requiring IV antibiotics.
11. Have positive human immunodeficiency virus (HIV)-1 or HIV-2 antibody with detectable viral load or taking medications that may interfere with SN-38 (the active metabolite of sacituzumab govitecan).
12. Have active hepatitis B virus (HBV) or hepatitis C virus (HCV), subjects with a detectable viral load will be excluded. 12.1 Subjects who test positive for hepatitis B surface antigen (HBsAg). Subjects who test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by quantitative polymerase chain reaction (PCR) for confirmation of active disease. 12.2 Subjects who test positive for HCV antibody. Subjects who test positive for HCV antibody will require HCV RNA by quantitative PCR for confirmation of active disease. Subjects with a known history of HCV or a positive HCV antibody test will not require an HCV antibody at screening and will only require HCV RNA by quantitative PCR for confirmation of active disease.
13. 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.
14. Impending need for palliative radiation therapy or surgery for pathological fractures and/or for medullary compression within 4 weeks prior to initiating study treatment
15. Additional cohort-specific exclusion criteria:- NSCLC cohort (adenocarcinoma and SCC): 15.1 Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc); any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren syndrome, sarcoidosis, etc); or prior pneumonectomy. - HNSCC cohort: 15.2 Subjects with nasopharynx carcinoma. 15.3 Subjects who had progressive disease within 6 months of completion of curative therapy. - Endometrial carcinoma cohort: 15.4 Subjects who have carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma, and/or endometrial stromal sarcomas. - Small cell lung cancer cohort: 15.5 Subjects who never received platinum-containing regimen for SCLC. 15.6 Limited-stage subjects who are candidates for local or regional therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR) according to RECIST 1.1 by Investigator's assessment.

Secondary endpoints 5

1. ORR, DOR, CBR, and PFS according to RECIST 1.1 by BICR.
2. DOR, CBR, and PFS, according to RECIST 1.1 by Investigator's assessment.
3. Overall survival (OS).
4. Incidence of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities.
5. Serum concentrations of sacituzumab govitecan over time and incidence of anti-drug antibody (ADA) to sacituzumab govitecan.

Investigational products

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

Test 1

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 Clinical Trials Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU Clinical Trials Support

Third parties 2

Locations

3 EU/EEA countries · 10 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

Documents 9 files

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

Application history

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