A Phase 1 Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation

INCB099280 is a PD-L1 inhibitor. Adagrasib is a KRAS inhibitor (G12C).

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

• How much of the study drug can be given with an acceptable level of side effects
• The effects of the study drug (good and bad)
• How much of the study drug is absorbed into the blood and how fast it is removed
• How the study drug is acting on your body

This is a dose escalation/expansion study that will be completed in two parts, Part 1 and Part 2.

Part 1 of the study is called dose escalation which means that the amount of study drug 1 will be increased in combination with a fixed dose of study drug 2 in each group of research participants, to find the most appropriate dose for further study. For some participants enrolled in Part 1 of the trial, there will be an 8 day “lead-in”. Participants in this “lead-in” will receive study drug 1, INCB099280 alone for 8 days before starting the combination regimen. This “lead-in” is to allow evaluation of blood levels of study drug 1 both with and without Adagrasib. Your study doctor will let you know if you will take part in the “lead-in”.

Part 2 of the study is called dose expansion, where a larger number of people receive the study drug combination at the dose level determined to be appropriate in the dose escalation part of the study.

The dose of the study s you receive will be determined when you enter the study.

The study regimen will be given in cycles.  Each cycle is 28 days. During weeks 1-8 you will visit the clinic every week. During weeks 9-16 you will visit the clinic every 2 weeks. From Week 17 on, you will visit the clinic every 4 weeks. Visits will range from a couple of hours to a whole day in length depending on what tests/procedures are being performed. You could be asked to have more examinations and/or tests in order to ensure your safety and health.  Study drug 1 is provided as tablets and will need to be stored in the refrigerator.  Study drug 1 may be taken by mouth in the morning and at night or once daily as instructed.  The site will instruct you on when the study drug 1 tablets must be taken. Study drug 2 is provided as tablets and will be stored at room temperature.   Study drug 2 must be taken by mouth at about the same time of day every day in the morning and at night. The doses should be taken about 12 hours apart. On certain visit days, you will take the Investigational combination tablets in clinic, not at home.