A Phase 1 Study of the Safety and Tolerability of COM902 in Subjects with Advanced Malignancies

COM902 is a monoclonal antibody that binds to TIGIT, an inhibitory signal molecule on lymphocytes. The binding of TIGIT, either alone or in combination with a PVRIG (COM701) or PD-1 inhibitor, may enhance antigen-specific human T cell responses., COM701 is a monoclonal antibody against the poliovirus receptor-related immunoglobulin (PVRIG; PVR Related Immunoglobulin Domain Containing Protein; CD112R), a regulatory signal molecule expressed on cytotoxic T lymphocytes and NK cells. Blockade of PVRIG can prevent PVRIG-induced inhibition of T-lymphocyte and NK-cell activation. This sequence could enhance anti-tumor responses and immune-mediated tumor cell killing.

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

• How much of study  1 (COM902) can be given alone and in combination with study agent 2 (COM701) and Pembrolizumab with an acceptable level of side effects
• The effects of the study agent (good and bad)
• How much of the study agent is absorbed into the blood and how fast it is removed
• If research tests can be used in the future to predict who will benefit from the study agent 1 and/or study agent 2

In this study, research participants will be assigned to receive study  1 in combination with study agent 2 and Pembrolizumab.

This is a dose escalation/expansion study and will be conducted in five parts:

• Study agent 1 Monotherapy Dose Escalation
• Study agent 1 Monotherapy Dose Expansion
• Study agent 1 + Study agent 2 Dual Combination Dose Escalation
• Study agent 1 + Study agent 2 Dual Combination Dose Expansion
• Study agent 1 + Study agent 2 + Pembrolizumab Triplet Combination Dose Expansion

Monotherapy Dose Escalation Phase: The amount of the study  1 given was increased in each group of research participants, to find the most appropriate dose for further study. The dose escalation phase of the study has been completed.

Monotherapy Dose Expansion Phase: The recommended dose of study agent 1 from the Dose Escalation Phase will be given alone. This phase of the study is closed to further enrollment.

Dual Combination Dose Escalation Phase: The recommended dose of study agent 1 will be given with study agent 2 to find the most appropriate dose combination for further study. This phase of the study is closed to further enrollment.

Dual Combination Dose Expansion Phase: A larger number of people receive the study agent 1 dose determined to be appropriate in the dose escalation parts of the study in combination with study agent 2. This phase of the study is closed to further enrollment.

As this is the first time that the 3 study drugs will be tested together. The initial evaluation for safety and tolerability will be in up to 6 participants [at least 3 participants]. The third or sixth participant will have been on the combination for at least 3 weeks so your study doctor and sponsor can be able to determine if the combination is safe and tolerable. This phase of the study is closed to further enrollment.

If the triplet combination is deemed safe and tolerable, the study will proceed to the Triplet Combination Dose Expansion phase.

Triplet Combination Dose Expansion Phase: Groups of research participants will be assigned to 1 of 2 cohorts depending on their type of cancer. All participants will receive study agent 1 in combination with study agent 2 and Pembrolizumab.

The study treatment will be given in cycles. Each cycle is 21 days. If you are enrolled into the dual combination part of the study, you will receive study agent 1 followed by study agent 2, on Day 1 of each cycle as an IV infusion over about 1 hour. If you are enrolled into the triplet combination part of the study, you will receive study agent 1 followed by study agent 2 and then Pembrolizumab, on Day 1 of each cycle as an IV infusion over about 1.5 hours.