Study of Olomorasib (LY3537982) in Combination With Standard of Care in Participants With Resected or Unresectable KRAS G12C-mutant Non-Small Cell Lung Cancer
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT06890598
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The main purpose of this study is to assess if olomorasib in combination with pembrolizumab is more effective than the pembrolizumab and placebo combination in part A in participants with resected KRAS G12C-mutant NSCLC and to assess if olomorasib in combination with durvalumab is more effective than the durvalumab and placebo combination in part B in participants with unresectable KRAS G12C-mutant non-small cell lung cancer. The study may last up to 3 years for each participant.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 700
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Histological or cytological confirmation of NSCLC.
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Part A
- Clinical Stage II-IIIB (N2) treated with presurgical chemoimmunotherapy, with residual tumor present at time of surgery. Patients with a pathologic complete response are not eligible.
- Pathologic Stage II-IIIB (N2) NSCLC treated with initial upfront resection.
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Part B - Clinical Stage III, unresectable NSCLC, without progression on concurrent platinum-based chemoradiotherapy.
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Must have disease with evidence of KRAS G12C mutation.
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Must have known programmed death-ligand 1 (PD-L1) expression
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Must have an ECOG performance status of 0 or 1.
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Able to swallow oral medication.
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Must have adequate laboratory parameters.
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Contraceptive use should be consistent with local regulations for those participating in clinical studies.
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Women of childbearing potential must
- Have a negative pregnancy test.
- Not be breastfeeding during treatment
- Have known changes in the EGFR or ALK genes.
- Have another type of cancer that is progressing or required active treatment within the past 3 years before screening.
- Have an active autoimmune disease that required systemic treatment in the past 2 years. Endocrine replacement therapy is allowed.
- Had any immune-related side effect or allergic reaction (Grade 3 or higher) from a previous immunotherapy medicine, or any immune-related side effect greater than Grade 1 that has not resolved. This does not apply for people with hormone-related diseases who are now on stable hormone replacement therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Olomorasib + Pembrolizumab Olomorasib Participants will receive olomorasib administered orally in combination with pembrolizumab intravenously (IV) for up to 1 year followed by olomorasib alone for up to 3 years of total treatment. Part A: Olomorasib + Pembrolizumab Pembrolizumab Participants will receive olomorasib administered orally in combination with pembrolizumab intravenously (IV) for up to 1 year followed by olomorasib alone for up to 3 years of total treatment. Part A: Placebo + Pembrolizumab Pembrolizumab Participants will receive placebo administered orally in combination with pembrolizumab administered IV for up to 1 year followed by placebo alone for up to 3 years of total treatment. Part A: Placebo + Pembrolizumab Placebo Participants will receive placebo administered orally in combination with pembrolizumab administered IV for up to 1 year followed by placebo alone for up to 3 years of total treatment. Part B: Olomorasib + Durvalumab Olomorasib Participants will receive olomorasib administered orally in combination with durvalumab administered IV for up to 1 year followed by olomorasib alone for up to 3 years of total treatment. Part B: Olomorasib + Durvalumab Durvalumab Participants will receive olomorasib administered orally in combination with durvalumab administered IV for up to 1 year followed by olomorasib alone for up to 3 years of total treatment. Part B: Placebo + Durvalumab Durvalumab Participants will receive placebo administered orally in combination with durvalumab administered IV for up to 1 year followed by placebo alone for up to 3 years of total treatment. Part B: Placebo + Durvalumab Placebo Participants will receive placebo administered orally in combination with durvalumab administered IV for up to 1 year followed by placebo alone for up to 3 years of total treatment.
- Primary Outcome Measures
Name Time Method Part B: Progression-Free Survival (PFS) Randomization to disease progression or death from any cause (Estimated as approximately 3 years). PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR)
Part A: Disease-Free Survival (DFS) by Investigator Assessment Randomization to disease recurrence or death from any cause (Estimated as approximately 48 months). DFS by Investigator Assessment
- Secondary Outcome Measures
Name Time Method Part A & B: Overall Survival (OS) Randomization to disease progression or death from any cause (Estimated as approximately 5 years). OS
Part A & B: Change from baseline in health-related quality of life (HRQoL), measured by European Organization for Research & Treatment of CancerQualityofLifeQuestionnaire-Core 30 (EORTC QLQ-C30) Randomization through end of treatment (Estimated as approximately 3 years). Change from baseline in HRQoL, measured by the EORTC QLQ-C30
Part B: Objective Response Rate (ORR) per RECIST 1.1 by BICR Randomization to disease progression or death from any cause (Estimated as approximately 3 years). ORR per RECIST 1.1 by BICR
Part B: Duration of Response (DOR) per RECIST 1.1 by BICR Randomization to disease progression or death from any cause (Estimated as approximately 3 years). DOR per RECIST 1.1 by BICR
Part B: Disease Control Rate (DCR) per RECIST 1.1 by BICR Randomization to disease progression or death from any cause (Estimated as approximately 3 years). DCR per RECIST 1.1 by BICR
Part B: Changes in Non-Small Cell Lung Cancer (NSCLC)-related symptoms, measured by the NSCLC-Symptom Assessment Questionnaire (SAQ) Randomization through end of treatment (Estimated as approximately 3 years). Changes in NSCLC-related symptoms, measured by the NSCLC-SAQ
Part B: Time to worsening of NSCLC-related symptoms, as measured by NSCLC-SAQ Randomization through end of treatment (Estimated as approximately 3 years). Time to worsening of NSCLC-related symptoms, as measured by NSCLC-SAQ
Part B: Changes in patient-reported pulmonary symptoms of cough, chest pain, and dyspnea, measured by NSCLC-SAQ Randomization through end of treatment (Estimated as approximately 3 years). Changes in patient-reported pulmonary symptoms of cough, chest pain, and dyspnea, measured by NSCLC-SAQ
Part B: Time to Response (TTR) per RECIST 1.1 by BICR Randomization until the date that measurement criteria for CR or PR (whichever is first recorded) are first met (Estimated as approximately 3 years). TTR per RECIST 1.1 by BICR
Part B: Progression-Free Survival 2 (PFS2) by investigator assessment Randomization to disease progression on next line of treatment or death from any cause (Estimated as approximately 3 years).] PFS2 by investigator assessment
Related Research Topics
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Trial Locations
- Locations (344)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Clearview Cancer Institute
🇺🇸Huntsville, Alabama, United States
The University of Arizona Cancer Center - North Campus
🇺🇸Tucson, Arizona, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
UCLA Hematology/Oncology - Santa Monica
🇺🇸Los Angeles, California, United States
Profound Research LLC
🇺🇸Oceanside, California, United States
University of California, Irvine (UCI) Health - UC Irvine Medical Center
🇺🇸Orange, California, United States
Stanford Cancer Center
🇺🇸Palo Alto, California, United States
Kaiser Permanente San Diego Mission Road
🇺🇸San Diego, California, United States
BASS Cancer Center
🇺🇸Walnut Creek, California, United States
Scroll for more (334 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United StatesMaya KhalilPrincipal Investigator