A Phase 1a/1b Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors
- Study HIC#:2000031441
- Last Updated:04/19/2024
The purpose of this study is to find out whether the study drug, LY3537982, is safe and effective in cancer patients who have a specific genetic mutation (KRAS G12C). Patients must have already received or were not able to tolerate the standard of care. The study will last up to approximately 2 years.
Contact Us
For more information about this study, including how to volunteer, contact:
Ingrid Palma
- Phone Number: 1-203-785-6431
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Trial Purpose and Description
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.
Eligibility Criteria
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.