A Phase 1a/1b Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors

This is an open-label, multicenter Phase 1 study to evaluate safety, tolerability, and preliminary efficacy of oral LY3537982 in patients with KRAS G12C-mutant solid tumors.

This study will be conducted in 2 parts, Part 1a is a dose escalation and Part 1b is a dose expansion. Part 1a will establish a recommended Phase 2 dose. Part 1b will have multiple arms of either monotherapy or in combination with other drugs.

KRAS G12C mutations will be identified through standard of care testing.

Inclusion Criteria:

• Patients have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or circulating tumor deoxyribonucleic acid (DNA).
• Participants must have a histological or a cytologically proven diagnosis of locally advanced, unresectable, and/or metastatic cancer and meet cohort-specific criteria.
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Have adequate organ function.
• Have discontinued all previous treatments for cancer with resolution of any significant ongoing adverse events (AEs).
• Must be able to swallow capsule/tablet.
• Agree and adhere to contraceptive use, if applicable.

Exclusion Criteria:

• Disease suitable for local therapy administered with curative intent.
• Have an active, ongoing, or untreated infection.
• Have a serious pre-existing medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
• Have a serious cardiac condition.
• Have a second active primary malignancy or have been diagnosed and/or treated for an additional malignancy within 3 years prior to enrollment.
• Have symptomatic central nervous system (CNS) malignancy or metastasis and/or carcinomatous meningitis. Patients with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids in excess of 10 milligrams (mg) per day prednisone/prednisolone (or equivalent) and their disease is asymptomatic and radiographically stable for at least 30 days.
• Have received prior treatment with any KRAS G12C small molecule inhibitor, except in certain scenarios where such prior therapy is allowed as per protocol.
• For Cohorts B2, B3, and B5/C1, patients treated with drugs known to be strong inhibitors or inducers of cytochrome P450 (CYP)3A.
• The following patients will be excluded from Cohort B4:
  • Experienced certain serious side effects with prior immunotherapy.
  • Have an active autoimmune disease that has required systemic anti-autoimmune treatment in the past 2 years.
  • Have received a live vaccine within 30 days prior to the first dose of study drug.
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 180 days after the last dose of study medication.
• Known allergic reaction against any of the components of the study treatments.
• The following patients will be excluded from Cohorts B7 & C3:
  • Clinically significant cardiac disease or risk factors at screening.