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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy — Cycle 1 (21 Days) Measured by the number of patients with dose-limiting toxicities (DLTs)
Phase 1b: To assess the safety and tolerability of LY3537982 when administered alone or in combination with other investigational agents — Cycle 1 (21 Days) Measured by the number of patients with dose-limiting toxicities (DLTs)
Phase 1b: To determine the optimal dose of LY3537982 to be administered to treatment-naïve participants with advanced NSCLC in combination with pembrolizumab — Estimated up to 2 years Measured by TEAEs
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
Trial sites (49)
Facility
City
Region
Status
University of Alabama at Birmingham
Birmingham
Alabama
USC Norris Cancer Hospital
Los Angeles
California
Chao Family Comprehensive Cancer Ctr.
Orange
California
Yale-New Haven Hospital
New Haven
Connecticut
AdventHealth Orlando
Orlando
Florida
Florida Cancer Specialists
Sarasota
Florida
Indiana Univ Melvin & Bren Simon Cancer Center
Indianapolis
Indiana
Community Health Network
Indianapolis
Indiana
Mary Bird Perkins Cancer Center
Baton Rouge
Louisiana
Massachusetts General Hospital
Boston
Massachusetts
Dartmouth-Hitchcock Medical Center
Lebanon
New Hampshire
NYU Langone Health- Long Island
Mineola
New York
NYU Langone
New York
New York
Memorial Sloan Kettering Cancer Center
New York
New York
The University of North Carolina at Chapel Hill
Chapel Hill
North Carolina
Novant Health Cancer Institute - Elizabeth
Charlotte
North Carolina
Novant Health Cancer Institute - Forsyth
Winston-Salem
North Carolina
Fox Chase Cancer Center
Philadelphia
Pennsylvania
UPMC Hillman Cancer Center
Pittsburgh
Pennsylvania
Sarah Cannon Cancer Center
Nashville
Tennessee
Vanderbilt Univeristy School of Medicine
Nashville
Tennessee
South Texas Accelerated Research Therapeutics (START)
San Antonio
Texas
START Mountain Region
West Valley City
Utah
Inova Health System IRB
Fairfax
Virginia
USO-Virginia Cancer Specialists, PC
Fairfax
Virginia
University of Wisconsin-Madison Hospital and Health Clinic
Madison
Wisconsin
Royal North Shore Hospital
St Leonards
New South Wales
St Vincent's Hospital Sydney
Sydney
New South Wales
Cancer Research SA
Adelaide
South Australia
Peninsula and Southeast Oncology
Frankston
Victoria
Linear Clinical Research
Nedlands
Western Australia
Cross Cancer Institute
Edmonton
Alberta
Princess Margaret Hospital (Ontario)
Toronto
Ontario
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
Bordeaux
Aquitaine
Centre Leon Berard
Lyon
Auvergne-Rhône-Alpes
Institut du Cancer de Montpellier - Val d'aurelle
Montpellier
France
Institut Claudius Regaud - IUCT Oncopole
Toulouse
France
Gustave Roussy
Villejuif
France
Aichi Cancer Center Hospital
Nagoya
Aichi-ken
National Cancer Center Hospital East
Kashiwa
Chiba
+ 9 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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