Solid Malignancies Clinical Trial
Official title:
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.
Status | Recruiting |
Enrollment | 195 |
Est. completion date | January 2027 |
Est. primary completion date | January 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
Israel | Rambam Health Care Campus | Haifa | |
Israel | Hadassah Medical Center- Ein Kerem | Jerusalem | |
Israel | Tel-Aviv Sourasky Medical Center | Tel Aviv | |
United States | University of Colorado Hospital - Anschutz Cancer Pavilion (ACP) | Aurora | Colorado |
United States | Montefiore Medial Center - Montefiore Medical Park | Bronx | New York |
United States | START Midwest | Grand Rapids | Michigan |
United States | Sarah Cannon Research Institute | Nashville | Tennessee |
United States | Oregon Health Oregon Health & Sciences University-Knight Cancer Institute | Portland | Oregon |
United States | START San Antonio | San Antonio | Texas |
United States | Moffitt Cancer Center | Tampa | Florida |
United States | START Mountain Region | West Valley City | Utah |
Lead Sponsor | Collaborator |
---|---|
Gilead Sciences |
United States, Israel,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Percentage of Patients Experiencing Dose-Limiting Toxicities (DLTs) | First dose date up to 21 days | ||
Primary | 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 | Maximum Observed Concentration (Cmax) for GS-9716 | Approximately 105 Weeks | ||
Secondary | Time to Maximum Observed Concentration (Tmax) for GS-9716 | Approximately 105 Weeks | ||
Secondary | Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) for GS-9716 | Approximately 105 Weeks | ||
Secondary | 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 | |
Secondary | 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 | |
Secondary | 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) | |
Secondary | 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) | |
Secondary | 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) |
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