Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Immunotherapy, KRAS, KRAS G12C, Targeted therapy
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
Interventions
DRUGAdagrasib
Specified dose on specified days
DRUGPembrolizumab
Specified dose on specified days
DRUGCarboplatin
Specified dose on specified days
DRUGPemetrexed
Specified dose on specified days
DRUGPlacebo
Specified dose on specified days
DRUGCisplatin
Specified dose on specified days
Sponsors
Mirati Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of non-squamous NSCLC with evidence of KRAS G12C mutation via tumor sample 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.
Exclusion criteria
* Participants with an active autoimmune or inflammatory disease requiring systemic treatment within 2 years. * Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment that are ongoing or with risk of recurrence. * 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Romania, Saudi Arabia, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed