Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GS-9716 as Monotherapy and in Combination With Anticancer Therapies in Adults With Solid Malignancies

NCT ID: NCT05006794

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-15
• Study Completion Date: 2029-03-31

Brief Summary

This is a Phase I open-label, multi-center study of zamzetoclax (formerly GS-9716) tested either as monotherapy or in combination with other anti-cancer agents in patients with advanced solid malignancies. Primary objectives are to define the maximum tolerated dose (MTD) or maximum administered dose of zamzetoclax, and characterize the safety and tolerability of zamzetoclax as monotherapy and in combination with anti-cancer therapies.

Conditions

Solid Malignancies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: zamzetoclax Dose-Escalation

Patients will receive escalating doses of zamzetoclax to estimate MTD.

Group Type: EXPERIMENTAL

zamzetoclax

Intervention Type: DRUG

Tablet(s) administered orally

Part A: zamzetoclax Dose-Expansion

Patients will receive ≤ MTD of zamzetoclax.

Group Type: EXPERIMENTAL

zamzetoclax

Intervention Type: DRUG

Tablet(s) administered orally

Part B (Cohort B1): Zamzetoclax + docetaxel

Patients will receive escalating doses of zamzetoclax in combination with docetaxel.

Group Type: EXPERIMENTAL

zamzetoclax

Intervention Type: DRUG

Tablet(s) administered orally

Docetaxel

Intervention Type: DRUG

Administered intravenously

Part B (Cohort B4): zamzetoclax + sacituzumab govitecan-hziy

Patients will receive escalating doses of zamzetoclax in combination with sacituzumab govitecan-hziy.

Group Type: EXPERIMENTAL

zamzetoclax

Intervention Type: DRUG

Tablet(s) administered orally

sacituzumab govitecan-hziy

Intervention Type: DRUG

Administered intravenously

Part C (Cohort C1): zamzetoclax + docetaxel

Patients will receive ≤ MTD zamzetoclax in combination with docetaxel.

Group Type: EXPERIMENTAL

zamzetoclax

Intervention Type: DRUG

Tablet(s) administered orally

Docetaxel

Intervention Type: DRUG

Administered intravenously

Part C (Cohort C4): zamzetoclax + sacituzumab govitecan-hziy

Patients will receive ≤ MTD zamzetoclax in combination with sacituzumab govitecan-hziy.

Group Type: EXPERIMENTAL

zamzetoclax

Intervention Type: DRUG

Tablet(s) administered orally

sacituzumab govitecan-hziy

Intervention Type: DRUG

Administered intravenously

Interventions

zamzetoclax

Tablet(s) administered orally

Intervention Type: DRUG

Docetaxel

Administered intravenously

Intervention Type: DRUG

sacituzumab govitecan-hziy

Administered intravenously

Intervention Type: DRUG

Other Intervention Names

GS-9716

Eligibility Criteria

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Measurable disease per RECIST version 1.1
• Adequate hematology, renal and hepatic function
• Left ventricular ejection fraction (LVEF) ≥ 50%
• Patients with brain metastases may be enrolled only if treated, nonprogressive, asymptomatic and not taking high dose steroids for at least 4 weeks prior to Cycle 1 Day 1 (C1D1)
• Individuals of childbearing potential who engage in heterosexual intercourse must agree to use method(s) of contraception, per protocol.
• Tissue criteria: must provide sufficient, and adequate tumor tissue sample or agree to have a biopsy taken.

• Histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor for which no standard therapy is available, standard therapy has failed, or for whom standard-of-care therapy is contraindicated.

• Histologically or cytologically confirmed unresectable metastatic or locally advanced disease following treatment for metastatic disease including an immune checkpoint inhibitor and a platinum-containing chemotherapy
• Patients with actionable genomic alterations must have also received treatment with at least 1 approved therapy appropriate to the genomic alteration unless unavailable or contraindicated

• Histologically or cytologically confirmed disease based on the most recent analyzed biopsy metastatic disease that is refractory to or relapsed after at least 2 prior standard-of-care chemotherapy regimens, one of which was a taxane (unless contraindicated).

Exclusion Criteria

• Prior systemic anti-cancer therapy must meet wash-out criteria outlined in protocol
• Treatment with any high dose systemic corticosteroids or nonsystemic radiotherapy within 2 weeks of the first dose of zamzetoclax (low dose corticosteroids permitted).
• Women who are pregnant or lactating
• Patients with active ≥ Grade 2 nausea or vomiting, and/or signs of intestinal obstruction
• Known active or chronic hepatitis B or C infection or HIV infection/ HIV positive
• Known history of clinically significant cardiovascular disease or heart failure.
• Known history of clinically significant active chronic obstructive pulmonary disease or other moderate to severe chronic respiratory illness present within 6 months prior to C1D1
• Known history of other clinically significant pulmonary disease or evidence of active pneumonitis
• Uncontrolled pleural effusion, pericardial effusion, or ascites
• History of clinically significant bleeding, intestinal obstruction, or gastrointestinal (GI) perforation within 6 months prior to C1D1
• Infection requiring intravenous anti-infective use within 2 weeks prior to C1D1
• Active or history of autoimmune disease or immune deficiency
• History of uncured coexisting cancer, not including uncured basal cell carcinoma, cervical cancer in situ, or superficial bladder cancer.

• Known heart failure or elevated cardiac biomarkers

• Known hypersensitivity to excipients in study treatments.

• Prior treatment with sacituzumab govitecan-hziy or a topoisomerase 1 inhibitor or agents targeting Trop-2.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, United States

Moffitt Cancer Center

Tampa, Florida, United States

START Midwest

Grand Rapids, Michigan, United States

Montefiore Medial Center - Montefiore Medical Park

The Bronx, New York, United States

Novant Health Cancer Institute - Elizabeth (Breast Cancer)

Charlotte, North Carolina, United States

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Oregon Health Oregon Health & Sciences University-Knight Cancer Institute

Portland, Oregon, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

START San Antonio

San Antonio, Texas, United States

START Mountain Region

West Valley City, Utah, United States

Rambam Health Care Campus

Haifa, , Israel

Hadassah Medical Center- Ein Kerem

Jerusalem, , Israel

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Countries

United States; Israel

Related Links

https://www.gileadclinicaltrials.com/study/?id=GS-US-467-5643

Gilead Clinical Trials Website

Other Identifiers

GS-US-467-5643

Identifier Type: -

Identifier Source: org_study_id