Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)

NCT ID: NCT04956640

Last Updated: 2025-09-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

540 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-19

Study Completion Date

2027-04-30

Brief Summary

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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, except for specific groups who have not had cancer treatment. The study will last up to approximately 4 years.

Detailed Description

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This is an open-label, multicenter Phase 1/2 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 4 parts: Phase 1a dose escalation, Phase 1b dose expansion, Phase 1b dose optimization, and Phase 2. KRAS G12C mutations will be identified through standard of care testing.

Conditions

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Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Endometrial Neoplasms Ovarian Neoplasms Pancreatic Neoplasms Biliary Tract Neoplasms

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LY3537982 (Dose Escalation)

LY3537982 administered orally.

Group Type EXPERIMENTAL

LY3537982

Intervention Type DRUG

Oral

LY3537982 (Dose Expansion)

LY3537982 administered orally either alone or with another investigational agent.

Group Type EXPERIMENTAL

LY3537982

Intervention Type DRUG

Oral

Pembrolizumab

Intervention Type DRUG

Intravenous

Cetuximab

Intervention Type DRUG

Intravenous

Pemetrexed

Intervention Type DRUG

Intravenous

Cisplatin

Intervention Type DRUG

Intravenous

Carboplatin

Intervention Type DRUG

Intravenous

LY3537982 (Dose Optimization)

LY3537982 administered orally either alone or with another investigational agent

Group Type EXPERIMENTAL

LY3537982

Intervention Type DRUG

Oral

Pembrolizumab

Intervention Type DRUG

Intravenous

Cetuximab

Intervention Type DRUG

Intravenous

Interventions

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LY3537982

Oral

Intervention Type DRUG

Pembrolizumab

Intravenous

Intervention Type DRUG

Cetuximab

Intravenous

Intervention Type DRUG

Pemetrexed

Intravenous

Intervention Type DRUG

Cisplatin

Intravenous

Intervention Type DRUG

Carboplatin

Intravenous

Intervention Type DRUG

Other Intervention Names

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Olomorasib KEYTRUDA® Erbitux LY231514 Alimta

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status RECRUITING

USC Norris Cancer Hospital

Los Angeles, California, United States

Site Status RECRUITING

Chao Family Comprehensive Cancer Ctr.

Orange, California, United States

Site Status RECRUITING

Yale-New Haven Hospital

New Haven, Connecticut, United States

Site Status RECRUITING

AdventHealth Orlando

Orlando, Florida, United States

Site Status RECRUITING

Florida Cancer Specialists

Sarasota, Florida, United States

Site Status RECRUITING

Indiana Univ Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status RECRUITING

Community Health Network

Indianapolis, Indiana, United States

Site Status RECRUITING

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status RECRUITING

NYU Langone Health- Long Island

Mineola, New York, United States

Site Status RECRUITING

NYU Langone

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Novant Health Cancer Institute - Elizabeth

Charlotte, North Carolina, United States

Site Status RECRUITING

Novant Health Cancer Institute - Forsyth

Winston-Salem, North Carolina, United States

Site Status RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Sarah Cannon Cancer Center

Nashville, Tennessee, United States

Site Status RECRUITING

Vanderbilt Univeristy School of Medicine

Nashville, Tennessee, United States

Site Status RECRUITING

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, United States

Site Status RECRUITING

START Mountain Region

West Valley City, Utah, United States

Site Status RECRUITING

Inova Health System IRB

Fairfax, Virginia, United States

Site Status RECRUITING

USO-Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status RECRUITING

University of Wisconsin-Madison Hospital and Health Clinic

Madison, Wisconsin, United States

Site Status RECRUITING

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status RECRUITING

St Vincent's Hospital Sydney

Sydney, New South Wales, Australia

Site Status RECRUITING

Cancer Research SA

Adelaide, South Australia, Australia

Site Status RECRUITING

Peninsula and Southeast Oncology

Frankston, Victoria, Australia

Site Status RECRUITING

Linear Clinical Research

Nedlands, Western Australia, Australia

Site Status RECRUITING

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status RECRUITING

Princess Margaret Hospital (Ontario)

Toronto, Ontario, Canada

Site Status RECRUITING

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Bordeaux, Aquitaine, France

Site Status RECRUITING

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, France

Site Status RECRUITING

Institut du Cancer de Montpellier - Val d'aurelle

Montpellier, , France

Site Status RECRUITING

Institut Claudius Regaud - IUCT Oncopole

Toulouse, , France

Site Status RECRUITING

Gustave Roussy

Villejuif, , France

Site Status RECRUITING

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, Japan

Site Status RECRUITING

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Site Status RECRUITING

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Site Status RECRUITING

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, Japan

Site Status RECRUITING

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Site Status RECRUITING

Wakayama Medical University Hospital

Wakayama, , Japan

Site Status RECRUITING

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

Site Status RECRUITING

The Catholic University of Korea, St. Vincent's Hospital

Suwon, Gyeonggi-do, South Korea

Site Status RECRUITING

Chonnam National University Hwasun Hospital

Hwasun-gun, Jeonranamdo, South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, Korea, South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, Korea, South Korea

Site Status RECRUITING

Countries

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United States Australia Canada France Japan South Korea

Central Contacts

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Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

Role: CONTACT

1-317-615-4559

Physicians interested in becoming principal investigators please contact

Role: CONTACT

Related Links

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https://trials.lilly.com/en-US/trial/295242

Study of LY3537982 in Cancer Patients with a Specific Genetic Mutation (KRAS G12C)

Other Identifiers

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2021-000595-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

J3M-OX-JZQA

Identifier Type: OTHER

Identifier Source: secondary_id

MK-3475-E27/KEYNOTE E27

Identifier Type: OTHER

Identifier Source: secondary_id

2022-502756-31-00

Identifier Type: CTIS

Identifier Source: secondary_id

LOXO-RAS-20001

Identifier Type: -

Identifier Source: org_study_id

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