Ph 1 Study of PF-07934040 in Subjects with Adv Solid Tumors with KRAS Mutation

This study is divided in two parts: Part 1 and Part 2. The goal of Part 1 is to determine the maximum tolerated dose (MTDM - the highest dose that is safe and tolerable for study participants) and the recommended dose for expansion (RDEM - the dose to give to many other participants) for the study drug when it is taken on its own. The goal of Part 2 is to see how well the study drug works against your cancer when it is take on its own or taken in combination with other cancer drugs. The part of the study in which you participate will depend on when you join the study. In addition, each part of the study has multiple cohorts. Your cohort assignment in Part 1 will depend on when you join the study, and your assignment in Part 2 will depend on what type of cancer you have. Part 1 Part 1 will have multiple cohorts:

• Cohort A: If you are in this cohort, you will get doses of the study drug that start low and slowly increase as each dose level is confirmed to be safe and tolerable until we find the MTDM.
• Cohort B: If you are in this cohort, you will get the study drug at the MTDM to confirm that the RDEM is safe and tolerable in a broader range of participants.
• Cohort C: If you are in this cohort, you will have two tumor biopsies done, one before you start taking the study drug and one while you are getting the study drug.
• Cohort D: If you are in this cohort, you will first take the study drug on an empty stomach for about 2 weeks. You will then switch to taking the study drug for one dose after eating, and then go back to taking it on an empty stomach. This will help us understand if taking the study drug with food changes the way it is absorbed into your body and whether it improves or worsens any potential side effects.
• Cohort E: This cohort will be an option if a specific cancer type shows early signs of improving with the study drug alone. This cohort is optional and dependent on what happens in cohorts A-D.

Part 2 In Part 2, we will look at not only safety and tolerability of the study drug, but also see if it stabilizes or improves cancer symptoms on its own or in combination with other drugs. This part also has multiple cohorts:

• Cohort A1: Participants who have pancreatic ductal adenocarcinoma (PDAC) with a KRAS mutation and have received two or three lines of treatment can join this cohort.
• Cohort B1: Participants who have colorectal cancer (CRC) with a KRAS mutation and have received two or three lines of treatment can joint this cohort.
• Cohort C1: Participants who have non-small cell lung cancer (NSCLC) with a KRAS mutation and have received two to three lines of treatment can join this cohort.

The study drug is a tablet that you will take by mouth. The strength (1 mg, 5 mg, or 25 mg) and number of the tablets provided will depend on which part and which cohort of the study you are enrolled in. You will take the study drug twice per day for as long as the study doctor believes is appropriate and beneficial for you.