Study of GS-9911 With or Without Antibody Treatment for Adults With Solid Tumors

Study Overview
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Brief Summary
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The main goal of this first in human (FIH) study is to learn about the safety and dosing of GS-9911 when given alone or in combination with an anti-programmed cell death protein 1 (PD-1) monoclonal antibody in participants with advanced solid tumors. The primary objectives of this study are to: Assess the safety and tolerability of GS-9911 as monotherapy and in combination with an anti-PD-1 monoclonal antibody in participants with advanced solid tumors Identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and the recommended dose for expansion (RDE) of GS-9911 as monotherapy and in combination with an anti-PD-1 monoclonal antibody in participants with advanced solid tumors

Official Title
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A Phase 1 Study to Evaluate the Safety and Tolerability of GS-9911 as Monotherapy and in Combination With an Anti-PD-1 Monoclonal Antibody in Adults With Advanced Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: GS-9911
* Drug: Zimberelimab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Parts A, C, and D: Participants with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or are ineligible for all treatments known to confer clinical benefit Part B: Participants whose cancer previously derived clinical benefit from immune checkpoint inhibitors, or who have advanced solid tumor types for which immune checkpoint inhibitors are considered the standard of care and who have received, been intolerant to, or are ineligible for all treatments known to confer clinical benefit Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Evaluable (Part A) or measurable (Parts B, C, and D) disease as per Response Criteria Evaluation in Solid Tumors (RECIST) v1.1 criteria Adequate organ functions Tissue requirement: Parts A-D: must be willing to provide baseline tumor tissue prior to enrollment Part A backfill cohorts: a biopsy should be obtained prior to treatment and on treatment, if safely feasible Participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception Exclusion Criteria: Positive serum pregnancy test or lactating female History of intolerance, hypersensitivity, or treatment discontinuation due to life- threatening immune-related adverse events on prior immunotherapy Receipt of the therapies listed below within the specified timeframe prior to planned Cycle 1 Day 1 including: major surgery (< 4 weeks), immunotherapy or biologic therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (<14 days or 5 half-lives, whichever is sooner), hormonal or other adjunctive therapy (< 14 days), radiation therapy (< 21 days), live vaccine (< 28 days) Any prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation Diagnosis of immunodeficiency, or requires systemic corticosteroids (> 10 mg of prednisone daily, or equivalent) History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years prior to the start of study drug History of pneumonitis requiring treatment with corticosteroids, interstitial lung disease, drug-induced pneumonitis, or severe radiation pneumonitis (excluding localized radiation pneumonitis) Active second malignancy. Note: individuals with a history of malignancy that have been completed treated, with no evidence of active cancer for 2 years prior to enrollment, or individuals with surgically cured tumors with low risk of recurrence are allowed to enroll. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis Symptomatic cardiovascular disease Active serious infection requiring ongoing treatment Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV. Symptomatic ascites or pleural effusion Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: GS-9911 Monotherapy Dose Escalation<br>Participants will receive escalating doses of GS-9911 monotherapy. | Drug: GS-9911<br>* Tablets administered orally<br>|
| Experimental: Part B: GS-9911 Monotherapy Dose Expansion<br>Participants will receive GS-9911 monotherapy at the recommended dose for expansion (RDE) determined in Part A. | Drug: GS-9911<br>* Tablets administered orally<br>|
| Experimental: Part C: Dose Escalation: GS-9911 + Anti-PD-1 Monoclonal Antibody<br>Participants will receive escalating doses of GS-9911 in combination with an anti-PD-1 monoclonal antibody (zimberelimab). | Drug: GS-9911<br>* Tablets administered orally<br>Drug: Zimberelimab<br>* Administered intravenously<br>|
| Experimental: Part D: Dose Expansion: GS-9911 + Anti-PD-1 Monoclonal Antibody<br>Participants will receive GS-9911 at RDE determined in Part C in combination with an anti-PD-1 monoclonal antibody (zimberelimab). | Drug: GS-9911<br>* Tablets administered orally<br>Drug: Zimberelimab<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment-emergent Adverse Events |  | First dose date up to 90 days post last dose (up to 105 weeks) | 
| Percentage of Participants With Treatment-emergent Serious Adverse Events |  | First dose date up to 90 days post last dose (up to 105 weeks) | 
| Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs) in Dose-escalation Cohorts |  | First dose date up to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of GS-9911 |  | Predose up to end of treatment (up to 105 weeks) | 
| Pharmacokinetic (PK) Parameter: Cmax of GS-9911 | Cmax is defined the maximum observed plasma drug concentration. | Predose up to end of treatment (up to 105 weeks) | 
| PK Parameter: Tmax of GS-9911 | Tmax is defined as the time to maximum observed concentration. | Predose up to end of treatment (up to 105 weeks) | 
| Area Under the Concentration-Time Curve (AUC) of GS-9911 | AUC is defined as the area under the concentration versus time curve. | Predose up to end of treatment (up to 105 weeks) |