A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT06875310
- Lead Sponsor
- Mirati Therapeutics Inc.
- Brief Summary
This is a trial to evaluate the efficacy, safety, and tolerability of adagrasib plus pembrolizumab plus platinum-doublet chemotherapy versus placebo plus pembrolizumab plus platinum-doublet chemotherapy in participants with previously untreated, locally advanced or metastatic NSCLC with KRAS G12C mutation
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 630
- Histologically or cytologically confirmed diagnosis of non-squamous NSCLC with evidence of KRAS G12C mutation via tumor tissue and/or circulating tumor deoxyribonucleic acid (ctDNA).
- Locally advanced or metastatic disease.
- Measurable disease via computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 criteria of at least 1 lesion.
- No prior systemic anti-cancer therapy given for advanced or metastatic disease.
- Not a candidate for definitive therapy (eg, chemoradiation or complete surgical resection).
- Participants with brain metastases are eligible for enrollment, including those with untreated brain metastases. Brain metastases must be asymptomatic and not in need of immediate local therapy. Any untreated brain metastases must be ≤ 20 mm in diameter.
- Any PD-L1 expression (0 to 100%) as determined by VENTANA PD-L1 (SP263) assay, Agilent PD-L1 IHC 22C3 pharmDx, or Agilent PD-L1 IHC 28-8 pharmDx.
- Participants with an active, known, prior documented, or suspected autoimmune or inflammatory disease.
- Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment.
- Inadequate bone marrow or liver function or electrocardiogram (ECG) abnormalities.
- Ongoing treatment with concomitant medication known to cause prolonged QTc interval and that cannot be switched to alternative treatment prior to study entry.
- Treatment targeting KRAS G12C mutation (eg, sotorasib, adagrasib) in any setting.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration.
- Other protocol-defined Inclusion/Exclusion criteria apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Adagrasib Adagrasib - Adagrasib Pembrolizumab - Adagrasib Carboplatin - Adagrasib Pemetrexed - Adagrasib Cisplatin - Placebo Pembrolizumab - Placebo Carboplatin - Placebo Pemetrexed - Placebo Placebo - Placebo Cisplatin -
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) as Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Blinded Independent Central Review (BICR) Up to 7 years Overall Survival (OS) Up to 7 years
- Secondary Outcome Measures
Name Time Method Overall Response (OR) as Assessed per RECIST v1.1 by BICR Up to 7 years Duration of Response (DOR) as Assessed per RECIST 1.1 by BICR Up to 7 years PFS as Assessed per RECIST v1.1 by Investigator Up to 7 years Number of Participants With Adverse Events (AEs) Up to 90 days from last dose Number of Participants With Serious Adverse Events (SAEs) Up to 90 days from last dose Number of Participants With AEs Leading to Dose Interruption Up to 90 days from last dose Number of Participants With AEs Leading to Dose Reduction Up to 90 days from last dose Number of Participants With AEs Leading to Treatment Discontinuation Up to 90 days from last dose Number of Deaths Up to 90 days from last dose Time to Definitive Deterioration by Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ) Total Score Up to 7 years Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) Scale/item Score Up to 90 days from last dose
Related Research Topics
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Trial Locations
- Locations (328)
Local Institution - 0347
🇺🇸Birmingham, Alabama, United States
Local Institution - 0581
🇺🇸Fullerton, California, United States
Local Institution - 0202
🇺🇸Long Beach, California, United States
Local Institution - 0643
🇺🇸Newport Beach, California, United States
Local Institution - 0666
🇺🇸Orange, California, United States
Local Institution - 0623
🇺🇸Santa Barbara, California, United States
Local Institution - 0442
🇺🇸Denver, Colorado, United States
Local Institution - 0651
🇺🇸Gainesville, Florida, United States
Local Institution - 0621
🇺🇸Palm Bay, Florida, United States
Local Institution - 0377
🇺🇸Tamarac, Florida, United States
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