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

A Phase 1a/b Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GS-9716 as Monotherapy and in Combination With Anticancer Therapies in Subjects With Solid Malignancies

This is a Phase I open-label, multi-center study of 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 GS-9716, and characterize the safety and tolerability of GS-9716 as monotherapy and in combination with anti-cancer therapies.

Study Overview

• Status: Recruiting
• Conditions: Solid Malignancies
• Intervention / Treatment: Drug: Docetaxel; Drug: GS-9716; Drug: sacituzumab govitecan-hziy

• Study Type: Interventional
• Enrollment (Estimated): 195
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Gilead Clinical Study Information Center; Phone Number: 1-833-445-3230 (GILEAD-0); Email: GileadClinicalTrials@gilead.com

Study Locations

• Israel
  • Haifa, Israel, 31096
    • Recruiting
    • Rambam Health Care Campus
  • Jerusalem, Israel, 91120
    • Recruiting
    • Hadassah Medical Center- Ein Kerem
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Tel-Aviv Sourasky Medical Center
• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • Start Midwest
  • New York
    • Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medial Center - Montefiore Medical Park
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health Oregon Health & Sciences University-Knight Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • START San Antonio
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • START Mountain Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

General Inclusion Criteria (all cohorts):

• 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.

Part A Specific Inclusion Criteria: GS-9716 as monotherapy

• 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.

Cohorts B1 and C1 Specific Inclusion Criteria:

• 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

Cohorts B4 and C4 Specific Inclusion Criteria:

• 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).

Key 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 GS-9716 (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.

Cohort A Specific Exclusion Criteria: GS-9716 as monotherapy:

• Known heart failure or elevated cardiac biomarkers

Cohorts B1 and C1 Specific Exclusion Criteria:

• Known hypersensitivity to excipients in study treatments.

Cohorts B4 and C4 Specific Exclusion Criteria:

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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: GS-9716 Dose-Escalation; Patients will receive escalating doses of GS-9716 to estimate MTD.	Drug: GS-9716; Tablet(s) administered orally
Experimental: Part A: GS-9716 Dose-Expansion; Patients will receive ≤ MTD of GS-9716.	Drug: GS-9716; Tablet(s) administered orally
Experimental: Part B (Cohort B1): GS-9716 + docetaxel; Patients will receive escalating doses of GS-9716 in combination with docetaxel.	Drug: Docetaxel; Administered intravenously; Drug: GS-9716; Tablet(s) administered orally
Experimental: Part B (Cohort B4): GS-9716 + sacituzumab govitecan-hziy; Patients will receive escalating doses of GS-9716 in combination with sacituzumab govitecan-hziy.	Drug: GS-9716; Tablet(s) administered orally; Drug: sacituzumab govitecan-hziy; Administered intravenously
Experimental: Part C (Cohort C1): GS-9716 + docetaxel; Patients will receive ≤ MTD GS-9716 in combination with docetaxel.	Drug: Docetaxel; Administered intravenously; Drug: GS-9716; Tablet(s) administered orally
Experimental: Part C (Cohort C4): GS-9716 + sacituzumab govitecan-hziy; Patients will receive ≤ MTD GS-9716 in combination with sacituzumab govitecan-hziy.	Drug: GS-9716; Tablet(s) administered orally; Drug: sacituzumab govitecan-hziy; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Patients Experiencing Dose-Limiting Toxicities (DLTs)	First dose date up to 21 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts B and C: Progression-Free Survival (PFS)	PFS is defined as the interval from the first dose of GS-9716 to the earlier of the first documentation of definitive progressive disease (PD) or death from any cause.	First dose date to PD or death, whichever occurs first (up to 39 months)
Parts B and C: Time to Response (TTR)	TTR is defined as the time from first dose of GS-9716 to the first documentation of CR or PR.	First dose date to the first documentation of CR or PR (up to 105 weeks)
Parts B and C: Duration of Response (DOR)	DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause.	From first documentation of CR or PR to PD or death, whichever occurs first (up to 37 months)
Maximum Observed Concentration (Cmax) for GS-9716		Approximately 105 Weeks
Time to Maximum Observed Concentration (Tmax) for GS-9716		Approximately 105 Weeks
Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) for GS-9716		Approximately 105 Weeks
Parts B and C: Objective Response Rate (ORR)	ORR is defined as the percentage of patients who achieve a confirmed complete response (CR) or confirmed partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Up to 105 weeks
Parts B and C: Disease Control Rate (DCR)	DCR is defined as the percentage of patients who achieve a CR, PR, or stable disease (SD) as assessed by RECIST version 1.1.	Up to 105 weeks

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 9, 2021
• First Posted (Actual): August 16, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Immunoconjugates; Docetaxel; Sacituzumab govitecan
• Other Study ID Numbers: GS-US-467-5643

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No