A Randomized, Double-Blind, Phase 3 Trial of Adagrasib plus Pembrolizumab plus Chemotherapy vs. Placebo plus Pembrolizumab plus Chemotherapy in Participants with Previously Untreated, Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer with KRASG12C Mutation.
Trial Snapshot
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 630
- Locations
- 15
- Primary Endpoint
- Progression free survival per RECIST v1.1 according to Blinded Independent Central Review (BICR)
Study Overview
Brief Summary
This study is a randomized, double-blind, placebo-controlled, Phase 3 clinical trial evaluating
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. Treatment will continue until confirmed PD, death, unacceptable toxicity, or withdrawal of consent.
All participants will have an End of Treatment (EOT) visit to collect safety and efficacy assessments. Once the participant
completes the end of treatment visit, they will enter the follow up period.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Masking
- Participant and Investigator Blinded
Eligibility Criteria
- Ages
- 18.00 Year(s) to 99.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •Histologically or cytologically confirmed diagnosis of non-squamous NSCLC
- •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)
- •Evidence of KRAS G12C mutation via tumor tissue and or ctDNA documented by Sponsor-approved laboratory testing
- •Any PD L1 expression (0 to 100 percentage ) as determined by VENTANA PD-L1 (SP263) assay, Agilent PD-L1 IHC 22C3 pharmDx or Agilent PD-L1 IHC 28-8 pharmDx. If despite best efforts a quantifiable result is not possible non-evaluable or non-quantifiable results may be acceptable upon Medical Monitor (or designee) approval for a maximum of 10 percentage of total participants.
- •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 less than or equal to 20 mm in diameter.
Exclusion Criteria
- •1.Participants with an active known prior documented or suspected autoimmune or inflammatory disease 2.Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment 3.Inadequate bone marrow function 4.Inadequate liver function 5.Ongoing treatment with concomitant medication known to cause prolonged QTc interval and that cannot be switched to alternative treatment prior to study entry 6.Treatment targeting KRAS G12C mutation (eg sotorasib adagrasib) in any setting 7.Certain significant ECG abnormalities 8.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug.
Outcomes
Primary Outcomes
Progression free survival per RECIST v1.1 according to Blinded Independent Central Review (BICR)
Time Frame: 1) Body scans Q6W until 1.5 years, then Q12W until BICR-confirmed progressive disease, even if the participant has discontinued study treatment. | 2) Brain imaging Q6W (if baseline brain metastases) or Q12W (if no baseline brain metastases) until 1.5 years, then Q12W.
Secondary Outcomes
- 1) Overall Response & Duration of Response per RECIST v1.1 according to BICR & progression free survival according to investigator.
Investigators
Shilpi Sinha
Bristol-Myers Squibb India Pvt. Ltd.