Clinical trial NCT05006794: Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GS-9716 as Monotherapy and in Combination With Anticancer Therapies in Adults With Solid Malignancies
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Malignancies
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2021-08-16
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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: zamzetoclax 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 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.

Cohort A Specific Exclusion Criteria: zamzetoclax 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.

Primary outcomes:
measure: Percentage of Patients Experiencing Dose-Limiting Toxicities (DLTs)
timeFrame: First dose date up to 28 days
measure: Percentage of Patients Experiencing Adverse Events (AEs) According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0
timeFrame: First dose date up to last dose date (Maximum: 105 weeks) plus 30 days
Secondary outcomes:
measure: Maximum Observed Concentration (Cmax) for Zamzetoclax
timeFrame: Approximately 105 Weeks
measure: Time to Maximum Observed Concentration (Tmax) for Zamzetoclax
timeFrame: Approximately 105 Weeks
measure: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) for Zamzetoclax
timeFrame: Approximately 105 Weeks
measure: Parts B and C: Objective Response Rate (ORR)
timeFrame: Up to 105 weeks
measure: Parts B and C: Disease Control Rate (DCR)
timeFrame: Up to 105 weeks
measure: Parts B and C: Progression-Free Survival (PFS)
timeFrame: First dose date to PD or death, whichever occurs first (up to 39 months)
measure: Parts B and C: Time to Response (TTR)
timeFrame: First dose date to the first documentation of CR or PR (up to 105 weeks)
measure: Parts B and C: Duration of Response (DOR)
timeFrame: From first documentation of CR or PR to PD or death, whichever occurs first (up to 37 months)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medial Center - Montefiore Medical Park
state: New York
city: Charlotte
country: United States
facility: Novant Health Cancer Institute - Elizabeth (Breast Cancer)
state: North Carolina
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health Oregon Health & Sciences University-Knight Cancer Institute
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: San Antonio
country: United States
facility: START San Antonio
state: Texas
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Medical Center- Ein Kerem
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: