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

• GS-GS-1811 is a monoclonal antibody that is designed to bind to CCR8. It is thought to target Tumor-Infiltrating T Regulatory cells for depletion by enhancing an antibody-dependent cellular cytotoxicity mechanism

In this study, the sponsor and investigators want to learn:

• How much of the study agent when given alone or in combination with Zimberelimab can be given with an acceptable level of side effects
• About the safety, tolerability, and effectiveness of the study agent when given alone or in combination with Zimberelimab
• Whether the study agent in combination with Zimberelimab or Zimberelimab alone is more effective
• How much of the study agent is absorbed into your blood and how fast it is removed from your blood
• If research tests can be used in the future to predict who will benefit from GS1811
• How your body responds to taking GS-1811 alone or in combination with Zimberelimab

In this study, research participants will be assigned to receive the study agent alone, in combination with zimberelimab or zimberelimab alone. 

This study has six parts, A, B, C, D, E and F. In the first part, Part A (dose escalation) the amount of study agent administered will initially be increased in each group of research participants, to find the most appropriate dose for further study.   

In Part A, not everyone will be receiving the same dose of study agent. A small group of participants (either 3 or 6) called a cohort will be given the same dose. If this group tolerates this dose well with few or easily manageable side effects, the next group will be given a higher dose.  

Part C will consist of two groups. The Safety Run-In group will test increasing doses of the study agent in combination with a set dose of zimberelimab to find the most appropriate dose (safest and most tolerable) of the study agent when used in combination with zimberelimab. In the Backfill group, the study agent will be administered in combination with zimberelimab at a dose that has deemed the most appropriate from the Safety Run-In group. This part of the study also requires some of the participants (up to 10) in the Backfill group to have the collection of tumor tissue biopsies which is described later in this consent. Your study doctor will let you know if you are one of the participants that will have your tumor tissue biopsy collected. 

In Part D of the study, depending on your type of cancer and the number of prior anti-cancer treatments you have received, you may be assigned to 1 of 4 groups in Part D (D1, D2, D3 or D4). Depending on what group you are assigned, you will be given GS-1811 in combination with zimberelimab or given zimberelimab alone. There will be about 156 participants in this Part D.  

• Part D1 is for participants with HNSCC where the cancer cannot be removed surgically, has come back when it had previously gone away (recurrent).  Participants in group D1 also cannot have had any prior anti-cancer treatment for their metastatic or recurrent HNSCC. There will be about 36 participants in this group. 

Participants in Part D1 will be randomly assigned (like the flip of a coin) to 1 of the 2 groups, Part D1a or Part D1b. Part D1a participants will receive GS-1811 with zimberelimab and Part D1b participants will receive zimberelimab alone. There will be about 24 participants in Part D1a and about 12 participants in Part D1b.  

• Randomization means the study drug(s) you take will be chosen by chance- like flipping a coin. You will have a 2 out of 3 chance to receive GS-1811 with zimberelimab and a 1 out of 3 chance to receive zimberelimab alone.  

• Part D2 is for participants with NSCLC who have received 1-3 prior anti-cancer treatments and will receive GS-1811 with zimberelimab. There will be about 40 participants in this group. 

• Part D3 is for participants with stomach cancer (gastric and esophagogastric junction [EGJ] adenocarcinoma) who have received 1-2 prior anti-cancer treatments and will receive GS-1811 with zimberelimab. There will be about 40 participants in this group. 

• Part D4 is for participants with metastatic colorectal cancer (mCRC). Metastatic means your cancer has spread to other parts of your body. Participants in this group will have already received treatment for their cancer and will receive GS-1811 with zimberelimab. There will be about 40 participants in this group. 

• Part E is for participants that have NSCLC, breast cancer (all types), vaginal cancer, cervical cancer, vulvar cancer, squamous cell cancer, and any other solid tumors the sponsor chooses. Participants in Part E will receive GS-1811 alone. There will be about 30 participants in this group. 

All Parts: 

The group you participate in is decided based on when you join the study and the type of cancer you have. Your study doctor will tell you which agent(s) you will receive and at what dosage(s). The dose of study agent you receive will depend on when you enter the study, how many participants have been in the study before you, and/or the side effects they had. Your study doctor will tell you what dose you will receive and how this dose compares to the doses other study participants have received.  

Your dose of study drug(s) may be temporarily stopped, changed (increased or decreased), or permanently stopped. This might happen if needed for your health or decided by your study doctor or the study sponsor. Your study doctor will discuss this with you before a change is made. If you are in a Backfill Group, your on-study treatment biopsy must be collected before your dose is changed. 

If you are receiving the study agent alone and your disease worsens, you may become eligible to receive GS-1811 in combination with Zimberelimab, this would be considered the Crossover Phase. Your study doctor will tell you if this is an option for you. There is a separate informed consent form for the Crossover Phase.  

The study treatment will be given in cycles.  Each cycle is 3 weeks. If you will be receiving the study agent alone, GS-1811 will be given on Day 1 of each cycle as an IV infusion over 60 minutes.  

If you will be receiving zimberelimab alone, zimberelimab will be given on Day 1 of each cycle as an IV infusion over 60 minutes. 

If you will be receiving the study agent in combination with zimberelimab, the study agent will be given first on Day 1 of each cycle as an IV infusion over 60 minutes, followed by a 1-hour observation period, and then zimberelimab will be given as an IV infusion over 60 minutes.