LY3537982 for KRAS G12C-mutant advanced solid tumors

Inclusion criteria

• {"criterion_text":"- Individuals must be able to provide consent consistent with local regulations and be ≥ 18 years of age at the time of signing the informed consent form\n- Individuals must have measurable disease per RECIST v1.1\n- Individuals must have a solid tumor with a KRAS G12C mutation. Individuals with NSCLC who have progressed on a prior KRAS G12C inhibitor are allowed to enroll but must have KRAS G12C mutation confirmed on a blood or tumor sample collected within 3 months of discontinuing the KRAS G12C inhibitor.\n- \"Phase 1a Dose escalation: - Advanced solid tumor - Patients who are not candidates for approved treatment measures Phase 1b Dose expansion Part B: - Cohort B9: Individuals must have previously untreated advanced/metastatic NSCLC. One prior 21-day cycle of the KEYNOTE-189 regimen is allowed before enrollement. Patients must initiate study treatment at the dose levels specified for each planned combination agent. - Cohort B8: Individuals must have at least 1 untreated, active brain metastasis Phase 1b Dose expansion Part C and Dose Optimization Part H: - Individuals must have received at least one prior oxaliplatin or irinotecan-containing regimen for advanced/metastatic CRC Phase 1b Dose expansion Part D - Individuals must have an unresetable solid tumor with a KRAS G12C mutation that is not NSCLC, CRC, or pancreatic cancer Phase 1b Dose expansion Part E - Individuals must have been previously treated with a KRAS G12C inhibitor Phase 2 Part F - Individuals must have unresectable pancreatic cancer with a KRAS G12C mutation Phase 1b Dose Optimization Part G - Individuals must have previously untreated advanced/metastatic NSCLC. One prior 21-day cycle of pembrolizumab is allowed before enrollement.\n- Individuals must have an ECOG performance status of 0 or 1\n- Individuals must have adequate organ function, as measured by blood tests\n- Individuals must have stopped all previous cancer treatments and recovered from the major side effects"}

Exclusion criteria

• {"criterion_text":"- Individual must not have an active uncontrolled systemic bacterial, viral, fungal, or parasitic infection, or other clinically significant active disease process.\n- Individuals cannot have a second active primary malignancy.\n- Individuals cannot have untreated active CNS metastases and/or carcinomatous meningitis. This does not apply to cohort B8.\n- Individuals cannot have received prior KRAS G12C inhibitor therapy. This does not apply to Phase 1a Dose Escalation backfill, cohort E1, or cohort B4.\n- Individuals that have experienced certain immune-related adverse reactions cannot enroll to cohorts B4, B9, or Part G.\n- \"Individuals with the following cannot enroll to cohorts B4, B9, or Part G: - An active autoimmune disease - Received a live vaccine within 30 days of study treatment - Received an organ or tissue transplant - Received radiation treatment to lungs - Received prior systemic therapy (except as allowed in Inclusion Criteria #4) \"\n- Patients with measured or calculated creatinine clearance <45mL/min at Cycle 1 Day 1 or withing 48 hours of C1D1 are excluded from Cohort B9"}

Primary endpoints

• {"endpoint_text":"- Dose limiting toxicity (DLT) rate and DLT-equivalent toxicities","definition_or_measurement_approach":""}
• {"endpoint_text":"- Rates of TEAEs, SAEs, deaths, and clinical laboratory abnormalities","definition_or_measurement_approach":""}
• {"endpoint_text":"- Antitumor activity of LY3537982","definition_or_measurement_approach":"Antitumor activity to be evaluated (per protocol secondary objective) using Investigator-assessed RECIST v1.1 in Phase 1a/1b and IRC assessment in Phase 2 (Part F)."}

Secondary endpoints

• {"endpoint_text":"- ORR, BOR, DOR, TTR, DCR, PFS, OS, Intracranial ORR and DOR, Plasma concentration of LY3537982 as monotherapy and when administered in combination: PK parameters including, but not limited to, AUC, Cmax, Tmax, and degree of accumulation","definition_or_measurement_approach":"Tumor response endpoints (ORR, BOR, DOR, TTR, DCR, PFS, OS, intracranial ORR/DOR) assessed as per RECIST v1.1/IRC as applicable. PK parameters include AUC, Cmax, Tmax and degree of accumulation."}

France

Earliest CTIS Part Ii Submission Date

15-08-2024

Latest Decision Or Authorization Date

23-01-2026

Processing Time Days

526

Number Of Sites

5

Number Of Participants

200

Primary sponsor

Full Name

Eli Lilly & Co.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Third parties

• {"country":"United States","full_name":"Integris Bioservices LLC","duties_or_roles":"codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"codes: [1,12,13,2,3,4,5,6,7]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions Holdings LLC","duties_or_roles":"codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Molecular Pathology Laboratory Network Inc.","duties_or_roles":"codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Icon Development Solutions LLC","duties_or_roles":"codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Infinity Biologix LLC","duties_or_roles":"codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"codes: [7]","organisation_type":"Non-Pharmaceutical company"}