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

NCT04956640 | Recruiting Phase 1 FDA Drug

• 5 other identifiers: LOXO-RAS-200012021-000595-12J3M-OX-JZQAMK-3475-E27/KEYNOTE E272022-502756-31-00
• Study Type: interventional
• Target: 540
• Locations: 6 countries
• Sites: 49

Brief Summary

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.

Conditions

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

Keywords

Frontline; 1L; First Line

Outcome Measures

Primary Outcomes (5)

• Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy

  Measured by the number of patients with dose-limiting toxicities (DLTs)

  Cycle 1 (21 Days)

• Phase 1b: To assess the safety and tolerability of LY3537982 when administered alone or in combination with other investigational agents

  Measured by the number of patients with dose-limiting toxicities (DLTs)

  Cycle 1 (21 Days)

• Phase 1b: To determine the optimal dose of LY3537982 to be administered to treatment-naïve participants with advanced NSCLC in combination with pembrolizumab

  Measured by TEAEs

  Estimated up to 2 years

• To determine the optimal dose of LY3537982 to be administered to participants who have received at least one prior oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC in combination with cetuximab

  Estimated up to 2 years

• To assess the antitumor activity of LY3537982 monotherapy in participants with advanced pancreatic cancer with KRAS G12C mutation

  Estimated up to 2 years

Secondary Outcomes (11)

• To assess preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Objective response rate (ORR)

  Estimated up to 2 years

• To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Duration of Response (DOR)

  Estimated up to 2 years

• To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Best Overall Response (BOR)

  Estimated up to 2 years

• To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Time to response (TTR)

  Estimated up to 2 years

• To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Disease control rate (DCR)

  Estimated up to 2 years

Study Arms (3)

LY3537982 (Dose Escalation)

EXPERIMENTAL

LY3537982 administered orally.

Drug: LY3537982

LY3537982 (Dose Expansion)

EXPERIMENTAL

LY3537982 administered orally either alone or with another investigational agent.

Drug: LY3537982; Drug: Pembrolizumab; Drug: Cetuximab; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

LY3537982 (Dose Optimization)

EXPERIMENTAL

LY3537982 administered orally either alone or with another investigational agent

Drug: LY3537982; Drug: Pembrolizumab; Drug: Cetuximab

Interventions

LY3537982 DRUG

Oral

Also known as: Olomorasib

LY3537982 (Dose Escalation); LY3537982 (Dose Expansion); LY3537982 (Dose Optimization)

Pembrolizumab DRUG

Intravenous

Also known as: KEYTRUDA®

LY3537982 (Dose Expansion); LY3537982 (Dose Optimization)

Cetuximab DRUG

Intravenous

Also known as: Erbitux

LY3537982 (Dose Expansion); LY3537982 (Dose Optimization)

Pemetrexed DRUG

Intravenous

Also known as: LY231514, Alimta

LY3537982 (Dose Expansion)

Cisplatin DRUG

Intravenous

LY3537982 (Dose Expansion)

Carboplatin DRUG

Intravenous

LY3537982 (Dose Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (49)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

USC Norris Cancer Hospital

Los Angeles, California, 90033, United States

RECRUITING

Chao Family Comprehensive Cancer Ctr.

Orange, California, 92868, United States

RECRUITING

Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

RECRUITING

AdventHealth Orlando

Orlando, Florida, 32803, United States

RECRUITING

Florida Cancer Specialists

Sarasota, Florida, 34236, United States

RECRUITING

Indiana Univ Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

Community Health Network

Indianapolis, Indiana, 46250, United States

RECRUITING

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

NYU Langone Health- Long Island

Mineola, New York, 11501, United States

RECRUITING

NYU Langone

New York, New York, 10016, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Novant Health Cancer Institute - Elizabeth

Charlotte, North Carolina, 28204, United States

RECRUITING

Novant Health Cancer Institute - Forsyth

Winston-Salem, North Carolina, 27103, United States

RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Sarah Cannon Cancer Center

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt Univeristy School of Medicine

Nashville, Tennessee, 37212-6303, United States

RECRUITING

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229-3307, United States

RECRUITING

START Mountain Region

West Valley City, Utah, 84119, United States

RECRUITING

Inova Health System IRB

Fairfax, Virginia, 22031, United States

RECRUITING

USO-Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

RECRUITING

University of Wisconsin-Madison Hospital and Health Clinic

Madison, Wisconsin, 53792-4108, United States

RECRUITING

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

RECRUITING

St Vincent's Hospital Sydney

Sydney, New South Wales, 2010, Australia

RECRUITING

Cancer Research SA

Adelaide, South Australia, 5000, Australia

RECRUITING

Peninsula and Southeast Oncology

Frankston, Victoria, 3199, Australia

RECRUITING

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

RECRUITING

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

Princess Margaret Hospital (Ontario)

Toronto, Ontario, M4X 1K9, Canada

RECRUITING

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

Bordeaux, Aquitaine, 33076, France

RECRUITING

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, 69008, France

RECRUITING

Institut du Cancer de Montpellier - Val d'aurelle

Montpellier, 34298, France

RECRUITING

Institut Claudius Regaud - IUCT Oncopole

Toulouse, 31052, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, 464-8681, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

RECRUITING

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

RECRUITING

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, 920, Japan

RECRUITING

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

RECRUITING

Wakayama Medical University Hospital

Wakayama, 641-8510, Japan

RECRUITING

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

RECRUITING

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

Suwon, Gyeonggi-do, 16247, South Korea

RECRUITING

Chonnam National University Hwasun Hospital

Hwasun-gun, Jeonranamdo, 58128, South Korea

RECRUITING

Seoul National University Hospital

Seoul, Korea, 03080, South Korea

RECRUITING

Asan Medical Center

Seoul, Korea, 05505, South Korea

RECRUITING

Related Links

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

MeSH Terms

Conditions

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

Interventions

pembrolizumab; Cetuximab; Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Pancreatic Diseases; Biliary Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

1-317-615-4559; LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2021
• First Posted: July 9, 2021
• Study Start: July 19, 2021
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (26); AU (5); CA (2); FR (5); JP (6); KR (5)