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

NCT05006794 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: GS-US-467-5643
• Study Type: interventional
• Target: 145
• Locations: 2 countries
• Sites: 13

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

Outcome Measures

Primary Outcomes (2)

• Percentage of Patients Experiencing Dose-Limiting Toxicities (DLTs)

  First dose date up to 28 days

• Percentage of Patients Experiencing Adverse Events (AEs) According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0

  First dose date up to last dose date (Maximum: 105 weeks) plus 30 days

Secondary Outcomes (8)

• Maximum Observed Concentration (Cmax) for Zamzetoclax

  Approximately 105 Weeks

• Time to Maximum Observed Concentration (Tmax) for Zamzetoclax

  Approximately 105 Weeks

• Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) for Zamzetoclax

  Approximately 105 Weeks

• Parts B and C: Objective Response Rate (ORR)

  Up to 105 weeks

• Parts B and C: Disease Control Rate (DCR)

  Up to 105 weeks

Study Arms (6)

Part A: zamzetoclax Dose-Escalation

EXPERIMENTAL

Patients will receive escalating doses of zamzetoclax to estimate MTD.

Drug: zamzetoclax

Part A: zamzetoclax Dose-Expansion

EXPERIMENTAL

Patients will receive ≤ MTD of zamzetoclax.

Drug: zamzetoclax

Part B (Cohort B1): Zamzetoclax + docetaxel

EXPERIMENTAL

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

Drug: zamzetoclax; Drug: Docetaxel

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

EXPERIMENTAL

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

Drug: zamzetoclax; Drug: sacituzumab govitecan-hziy

Part C (Cohort C1): zamzetoclax + docetaxel

EXPERIMENTAL

Patients will receive ≤ MTD zamzetoclax in combination with docetaxel.

Drug: zamzetoclax; Drug: Docetaxel

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

EXPERIMENTAL

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

Drug: zamzetoclax; Drug: sacituzumab govitecan-hziy

Interventions

sacituzumab govitecan-hziy DRUG

Administered intravenously

Part B (Cohort B4): zamzetoclax + sacituzumab govitecan-hziy; Part C (Cohort C4): zamzetoclax + sacituzumab govitecan-hziy

zamzetoclax DRUG

Tablet(s) administered orally

Also known as: GS-9716

Part A: zamzetoclax Dose-Escalation; Part A: zamzetoclax Dose-Expansion; Part B (Cohort B1): Zamzetoclax + docetaxel; Part B (Cohort B4): zamzetoclax + sacituzumab govitecan-hziy; Part C (Cohort C1): zamzetoclax + docetaxel; Part C (Cohort C4): zamzetoclax + sacituzumab govitecan-hziy

Docetaxel DRUG

Administered intravenously

Part B (Cohort B1): Zamzetoclax + docetaxel; Part C (Cohort C1): zamzetoclax + docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (13)

University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, 80045, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Montefiore Medial Center - Montefiore Medical Park

The Bronx, New York, 10467, United States

Location

Novant Health Cancer Institute - Elizabeth (Breast Cancer)

Charlotte, North Carolina, 28204, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health Oregon Health & Sciences University-Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

START San Antonio

San Antonio, Texas, 78229, United States

Location

START Mountain Region

West Valley City, Utah, 84119, United States

Location

Rambam Health Care Campus

Haifa, 31096, Israel

Location

Hadassah Medical Center- Ein Kerem

Jerusalem, 91120, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

Docetaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2021
• First Posted: August 16, 2021
• Study Start: September 15, 2021
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (10); IL (3)