Study of GS-1811 Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GS-1811 as monotherapy and in combination with Zimberelimab in participants with advanced solid tumors. This study will be conducted in 5 parts (Parts A, B, and E: monotherapy, Parts C and D: combination therapy), in participants with advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or in participants with select solid tumors.

Detailed Description
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Part D allocation for 1 cohort will be randomized.

Official Title
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A Phase 1 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of GS-1811, an Afucosylated Anti-CCR8 Monoclonal Antibody, as Monotherapy and in Combination With an Anti-PD-1 Monoclonal Antibody in Adults With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: GS-1811
* Drug: Zimberelimab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Disease: Part A: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit. Part B: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit. Part C: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or whose disease is indicated for anti-PD-(L)1 monoclonal antibody monotherapy. Part D: Individuals with pathologically confirmed select advanced solid tumors. Part E: Individuals with pathologically confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatment known to confer clinical benefit. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D and E. Adequate organ function. Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception. Tissue requirement: Parts A, C, D and E: Must provide pre-treatment adequate tumor tissue sample prior to enrolment. Part B: Must have fresh pre-treatment and on-treatment biopsy for biomarker analysis. Key Exclusion Criteria: Concurrent anticancer treatment. Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: immunotherapy or biologic therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14 days), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21 days). Any prior CCR8 directed therapy. Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Exception: prior corneal transplant without requirement for systemic immunosuppressive agents is allowed. Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected carcinoma in situ, localized prostate cancer, or superficial bladder cancer after undergoing potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease-free for > 2 years. History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy. History of autoimmune disease or active autoimmune disease requiring systemic treatment within 2 years. History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis). Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires IV antibiotics. Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV). Positive serum pregnancy test or breastfeeding female. Live vaccines within 30 days prior to first dose. Significant cardiovascular disease. 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-1811 Dose Escalation<br> | Drug: GS-1811<br>* Administered intravenously<br>|
| Experimental: Part B - Mandatory Paired Tumor Biopsy<br> | Drug: GS-1811<br>* Administered intravenously<br>|
| Experimental: Part C: GS-1811 + Zimberelimab dose escalation<br> | Drug: GS-1811<br>* Administered intravenously<br>Drug: Zimberelimab<br>* Administered intravenously<br>|
| Experimental: Part D: GS-1811 + Zimberelimab dose expansion<br> | Drug: GS-1811<br>* Administered intravenously<br>Drug: Zimberelimab<br>* Administered intravenously<br>|
| Experimental: Part E: GS-1811 Monotherapy Dose Expansion<br> | Drug: GS-1811<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 Experiencing Dose Limiting Toxicities (DLTs) |  | Day 1 Through Day 21 | 
| Percentage of Participants Experiencing Adverse Events (AEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 |  | First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days | 
| Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0 |  | First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for GS-1811 |  | Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days | 
| PK Parameter: Minimum Observed Concentration (Cmin) for GS-1811 |  | Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days | 
| PK Parameter: Time of Maximum Observed Concentration (Tmax) for GS-1811 |  | Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days | 
| PK Parameter: Area Under the Concentration-time Curve (AUC) for GS-1811 |  | Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days | 
| Percentage of Participants who Developed Antidrug Antibody (ADA) Against GS-1811 |  | Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days | 
| Objective response rate (ORR) | Objective response rate is defined as the proportion of participants who achieve complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Day 1 Up to End of Treatment (24 months) | 
| Disease control rate (DCR) | Disease control rate is defined as the proportion of participants who achieve CR, PR, or stable disease (SD) as assessed by RECIST Version 1.1 | Day 1 Up to End of Treatment (24 months) | 
| Time to response (TTR) | Time to response is defined as the time from the first dose of GS-1811 in combination with Zimberelimab to the first documentation of CR or PR that is subsequently confirmed | Day 1 Up to End of Treatment (24 months) | 
| Duration of response (DOR) | Duration of response is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of definitive progressive disease (PD) or death from any cause, if applicable. | Day 1 Up to End of Treatment (24 months) | 
| Progression-free survival (PFS) | Progression-free survival is defined as the time from the first dose of GS-1811 in combination with Zimberelimab to the earlier of the first documentation of definitive PD or death from any cause | Day 1 Up to End of Treatment (24 months) |