Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)
- Conditions
- Biliary Tract NeoplasmsCarcinoma, Non-Small-Cell LungColorectal NeoplasmsOvarian NeoplasmsEndometrial NeoplasmsPancreatic Neoplasms
- Interventions
- Registration Number
- NCT04956640
- Lead Sponsor
- Eli Lilly and Company
- 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 550
- 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.
-
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 180 days after the last dose of study medication.
-
Known allergic reaction against any of the components of the study treatments.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description LY3537982 (Dose Optimization) LY3537982 LY3537982 administered orally either alone or with another investigational agent LY3537982 (Dose Expansion) LY3537982 LY3537982 administered orally either alone or with another investigational agent. LY3537982 (Dose Escalation) LY3537982 LY3537982 administered orally. LY3537982 (Dose Expansion) Carboplatin LY3537982 administered orally either alone or with another investigational agent. LY3537982 (Dose Optimization) Pembrolizumab LY3537982 administered orally either alone or with another investigational agent LY3537982 (Dose Optimization) Cetuximab LY3537982 administered orally either alone or with another investigational agent LY3537982 (Dose Expansion) Pembrolizumab LY3537982 administered orally either alone or with another investigational agent. LY3537982 (Dose Expansion) Pemetrexed LY3537982 administered orally either alone or with another investigational agent. LY3537982 (Dose Expansion) Cetuximab LY3537982 administered orally either alone or with another investigational agent. LY3537982 (Dose Expansion) Cisplatin LY3537982 administered orally either alone or with another investigational agent.
- Primary Outcome Measures
Name Time Method 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 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)
To assess the antitumor activity of LY3537982 monotherapy in participants with advanced pancreatic cancer with KRAS G12C mutation Estimated up to 2 years 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
- Secondary Outcome Measures
Name Time Method 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 DOR
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) Estimated up to 2 years Intracranial DOR
To characterize the pharmacokinetics (PK) properties of LY3537982: Area under the plasma concentration versus time curve (AUC) Predose estimated up to 2 years PK: AUC of LY3537982
To characterize the PK properties of LY3537982: Maximum drug concentration (Cmax) Predose estimated up to 2 years PK: Cmax of LY3537982
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 ORR
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 BOR
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Progression-free survival (PFS) Estimated up to 2 years PFS
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 TTR
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 DCR
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Overall survival (OS) Estimated up to 2 years OS
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) Estimated up to 2 years Whole-body ORR
Trial Locations
- Locations (49)
Centre Leon Berard
🇫🇷Lyon, Rhône-Alpes, France
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Peninsula and Southeast Oncology
🇦🇺Frankston, Victoria, Australia
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Institut Claudius Regaud - IUCT Oncopole
🇫🇷Toulouse cedex, France
Aichi Cancer Center Hospital
🇯🇵Nagoya, Aichi, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
University of Wisconsin-Madison Hospital and Health Clinic
🇺🇸Madison, Wisconsin, United States
Gustave Roussy
🇫🇷Villejuif Cedex, France
Wakayama Medical University Hospital
🇯🇵Wakayama, Japan
National Cancer Center
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Chonnam National University Hwasun Hospital
🇰🇷Hwasun-gun, Jeonranamdo, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Korea, Republic of
The Catholic University of Korea, St. Vincent's Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Korea, Republic of
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Sarah Cannon Cancer Center
🇺🇸Nashville, Tennessee, United States
South Texas Accelerated Research Therapeutics (START)
🇺🇸San Antonio, Texas, United States
Vanderbilt Univeristy School of Medicine
🇺🇸Nashville, Tennessee, United States
Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Novant Health Cancer Institute - Forsyth
🇺🇸Winston-Salem, North Carolina, United States
USC Norris Cancer Hospital
🇺🇸Los Angeles, California, United States
Chao Family Comprehensive Cancer Ctr.
🇺🇸Orange, California, United States
Indiana Univ Melvin & Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Community Health Network
🇺🇸Indianapolis, Indiana, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
NYU Langone
🇺🇸New York, New York, United States
NYU Langone Health- Long Island
🇺🇸Mineola, New York, United States
The University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Novant Health Cancer Institute - Elizabeth
🇺🇸Charlotte, North Carolina, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
START Mountain Region
🇺🇸West Valley City, Utah, United States
USO-Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Inova Health System IRB
🇺🇸Fairfax, Virginia, United States
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Cancer Research SA
🇦🇺Adelaide, South Australia, Australia
St Vincent's Hospital Sydney
🇦🇺Sydney, New South Wales, Australia
Princess Margaret Hospital (Ontario)
🇨🇦Toronto, Ontario, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
🇫🇷Bordeaux, Aquitaine, France
Institut du Cancer de Montpellier - Val d'aurelle
🇫🇷Montpellier Cedex 5, France
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Kanazawa University Hospital
🇯🇵Kanazawa-shi, Ishikawa, Japan
Mary Bird Perkins Cancer Center
🇺🇸Baton Rouge, Louisiana, United States
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