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Treatment for cancer patients with a specific genetic mutation

A Phase 1/2 Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors

PHASE1; PHASE2 · Eli Lilly and Company · NCT04956640

This study is testing a new drug called LY3537982 to see if it can help cancer patients with a specific genetic mutation called KRAS G12C who haven't had success with standard treatments.

Quick facts

PhasePHASE1; PHASE2
Study typeInterventional
Enrollment540 (estimated)
Ages18 Years and up
SexAll
SponsorEli Lilly and Company (industry)
Drugs / interventionspembrolizumab, immunotherapy, radiation
Locations49 sites (Birmingham, Alabama and 48 other locations)
Trial IDNCT04956640 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of the drug LY3537982 in patients with solid tumors that have a KRAS G12C mutation. It is an open-label, multicenter Phase 1/2 trial that includes a dose escalation and expansion phase, followed by an optimization phase. Patients must have measurable disease and have either received standard treatment or been unable to tolerate it. The study aims to assess the drug's tolerability and preliminary efficacy over approximately four years.

Who should consider this trial

Good fit: Ideal candidates include patients with locally advanced, unresectable, or metastatic cancers that have the KRAS G12C mutation.

Not a fit: Patients without the KRAS G12C mutation or those who have not discontinued previous cancer treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new targeted therapy option for patients with KRAS G12C-mutant cancers.

How similar studies have performed: Other studies targeting KRAS mutations have shown promise, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion 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), (except in certain scenarios).
* Must be able to swallow capsule/tablet.
* Agree and adhere to contraceptive use, if applicable.
* For some parts of the study, (i.e., one of the two arms with LY3537982 in combination with pembrolizumab and the arm of LY3537982 in combination with pembrolizumab, pemetrexed, and platinum therapy) histologically or cytologically confirmed Stage IIIB-IIIC or Stage IV NSCLC that is previously untreated in the advanced/metastatic setting and not suitable for curative intent radical surgery or radiation therapy. Previously untreated patients who received adjuvant and neoadjuvant therapy are eligible if the last dose of the systemic treatment was completed at least 6 months prior to enrollment. For untreated patients in the arm with LY3537982 in combination with pembrolizumab noted above, a single cycle of pembrolizumab may be initiated within 21 days prior to enrollment. For untreated patients in the arm of LY3537982 in combination with pembrolizumab, pemetrexed, and platinum therapy, a single cycle of any or all of the drugs other than LY3537982 may be initiated within 21 days prior to enrollment. Start of study treatment may be delayed to allow sufficient time for recovery from treatment-related toxicity.
* For one part of the study, participants must have received at least one prior oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC.

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.
* For some parts of the study only: have untreated active central nervous system (CNS) metastases and/or leptomeningeal disease. Patients with treated CNS metastases are eligible for this study if their disease is asymptomatic, radiographically stable for at least 30 days, and they do not require treatment with steroids in the two-week period prior to study treatment. Patients with active CNS metastases are eligible for one part of the study.
* Have received prior treatment with any KRAS G12C small molecule inhibitor, except in certain scenarios where such prior therapy is allowed as per protocol.
* The following patients will be excluded from some parts of the study:

  * 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 35 days after the last dose of study medication.
* Known allergic reaction against any of the components of the study treatments.

Where this trial is running

Birmingham, Alabama and 48 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Endometrial Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Biliary Tract Neoplasms, Frontline, 1L

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.