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Carcinoma, Non-Small-Cell LungPhase 1/2NCT04956640

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

A Phase 1/2 study testing LY3537982, Pembrolizumab and Cetuximab in people with Carcinoma, Non-Small-Cell Lung and Colorectal Neoplasms, run by Eli Lilly and Company at 49 sites in 6 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
LY3537982, Pembrolizumab and Cetuximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
540 participants
Where
49 sitesin 6 countries
Study dates
19 Jul 2021to Apr 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

49 sites in 6 countries.

49 sites in 6 countries

United States26 sites

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • The University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Novant Health Cancer Institute - Elizabeth

    Charlotte, North Carolina, 28204

  • Inova Health System IRB

    Fairfax, Virginia, 22031

  • USO-Virginia Cancer Specialists, PC

    Fairfax, Virginia, 22031

  • Indiana Univ Melvin & Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Community Health Network

    Indianapolis, Indiana, 46250

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • USC Norris Cancer Hospital

    Los Angeles, California, 90033

  • University of Wisconsin-Madison Hospital and Health Clinic

    Madison, Wisconsin, 53792-4108

  • NYU Langone Health- Long Island

    Mineola, New York, 11501

  • Sarah Cannon Cancer Center

    Nashville, Tennessee, 37203

  • Vanderbilt Univeristy School of Medicine

    Nashville, Tennessee, 37212-6303

  • Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • NYU Langone

    New York, New York, 10016

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Chao Family Comprehensive Cancer Ctr.

    Orange, California, 92868

  • AdventHealth Orlando

    Orlando, Florida, 32803

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111-2497

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • South Texas Accelerated Research Therapeutics (START)

    San Antonio, Texas, 78229-3307

  • Florida Cancer Specialists

    Sarasota, Florida, 34236

  • START Mountain Region

    West Valley City, Utah, 84119

  • Novant Health Cancer Institute - Forsyth

    Winston-Salem, North Carolina, 27103

Other trials in United States

Japan6 sites

  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045

  • Kanazawa University Hospital

    Kanazawa, Ishikawa-ken, 920

  • National Cancer Center Hospital East

    Kashiwa, Chiba, 277-8577

  • Aichi Cancer Center Hospital

    Nagoya, Aichi-ken, 464-8681

  • Hokkaido University Hospital

    Sapporo, Hokkaido, 060-8648

  • Wakayama Medical University Hospital

    Wakayama, Wakayama, 641-8510

Other trials in Japan

Australia5 sites

  • Cancer Research SA

    Adelaide, South Australia, 5000

  • Peninsula and Southeast Oncology

    Frankston, Victoria, 3199

  • Linear Clinical Research

    Nedlands, Western Australia, 6009

  • Royal North Shore Hospital

    St Leonards, New South Wales, 2065

  • St Vincent's Hospital Sydney

    Sydney, New South Wales, 2010

Other trials in Australia

France5 sites

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

    Bordeaux, Aquitaine, 33076

  • Centre Leon Berard

    Lyon, Auvergne-Rhône-Alpes, 69008

  • Institut du Cancer de Montpellier - Val d'aurelle

    Montpellier, 34298

  • Institut Claudius Regaud - IUCT Oncopole

    Toulouse, 31052

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

South Korea5 sites

  • National Cancer Center

    Goyang-si, Gyeonggi-do, 10408

  • Chonnam National University Hwasun Hospital

    Hwasun-gun, Jeonranamdo, 58128

  • Seoul National University Hospital

    Seoul, Korea, 03080

  • Asan Medical Center

    Seoul, Korea, 05505

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

    Suwon, Gyeonggi-do, 16247

Other trials in South Korea

Canada2 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Princess Margaret Hospital (Ontario)

    Toronto, Ontario, M4X 1K9

Other trials in Canada

About this study

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

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.

Read the detailed description

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.

Being tested
LY3537982, Pembrolizumab, Cetuximab, Pemetrexed, Cisplatin
Keywords
Frontline, 1L, First Line
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Endometrial Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04956640
Study groupRoleWhat they receive
LY3537982 (Dose Escalation)ExperimentalLY3537982 administered orally.
Receives: Drug: LY3537982
LY3537982 (Dose Expansion)ExperimentalLY3537982 administered orally either alone or with another investigational agent.
Receives: Drug: LY3537982; Drug: Pembrolizumab; Drug: Cetuximab; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin
LY3537982 (Dose Optimization)ExperimentalLY3537982 administered orally either alone or with another investigational agent
Receives: Drug: LY3537982; Drug: Pembrolizumab; Drug: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: Cycle 1 (21 Days)

  2. 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)

    Measured: Cycle 1 (21 Days)

  3. 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

    Measured: Estimated up to 2 years

  4. 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

    Measured: Estimated up to 2 years

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

    Measured: Estimated up to 2 years

Secondary outcomes (11)

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

    ORR

    Measured: Estimated up to 2 years

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

    DOR

    Measured: Estimated up to 2 years

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

    BOR

    Measured: Estimated up to 2 years

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

    TTR

    Measured: Estimated up to 2 years

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

    DCR

    Measured: Estimated up to 2 years

  6. To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Progression-free survival (PFS)

    PFS

    Measured: Estimated up to 2 years

  7. To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Overall survival (OS)

    OS

    Measured: Estimated up to 2 years

  8. To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Intracranial DOR based on modified RECIST v1.1 (Certain arms of the study only)

    Intracranial DOR

    Measured: Estimated up to 2 years

  9. To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Whole-body ORR based on RECIST v1.1 and modified RECIST v1.1 (Certain arms of the study only)

    Whole-body ORR

    Measured: Estimated up to 2 years

  10. To characterize the pharmacokinetics (PK) properties of LY3537982: Area under the plasma concentration versus time curve (AUC)

    PK: AUC of LY3537982

    Measured: Predose estimated up to 2 years

  11. To characterize the PK properties of LY3537982: Maximum drug concentration (Cmax)

    PK: Cmax of LY3537982

    Measured: Predose estimated up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jul 2021
  2. Study start19 Jul 2021
  3. Primary completionApr 2027 (estimated)
  4. Study completionApr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
540 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04956640
Sponsor's protocol ID
LOXO-RAS-20001
Other IDs
2021-000595-12, J3M-OX-JZQA, MK-3475-E27/KEYNOTE E27, 2022-502756-31-00
Status last verified
Sep 2025
First submitted
2 Jul 2021
Last updated
29 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LY3537982, Pembrolizumab and Cetuximab in people with Carcinoma, Non-Small-Cell Lung and Colorectal Neoplasms, run by Eli Lilly and Company at 49 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, Japan, Australia, France, South Korea and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy (time frame: Cycle 1 (21 Days)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04956640.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2026.

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