Advanced NSCLC, Metastatic Lung Cancer
Conditions
Keywords
KRAS G12C, NSCLC, Non Small Cell Lung Cancer
Brief summary
Study CA239-0010 is an open-label, Phase 2 clinical trial evaluating the clinical efficacy of adagrasib in combination with pembrolizumab and chemotherapy in the first-line setting for patients with advanced NSCLC with TPS ≥ 1%, TPS \<50% and KRAS G12C mutation
Interventions
DRUGAdagrasib oral dose of 400 mg twice daily tablets
oral dose of 400 mg twice daily tablets
COMBINATION_PRODUCTPembrolizumab
IV infusion once every 3 weeks
COMBINATION_PRODUCTChemotherapy: Pemetrexed
IV infusion once every 3 weeks
COMBINATION_PRODUCTCisplatin/Carboplatin
IV infusion once every 3 weeks
Sponsors
Mirati Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Cohort A\* (closed): Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (squamous or nonsquamous) KRASG12C mutation and histologically confirmed PD-L1 TPS ≥1%. * Cohort C: Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (non-squamous only) KRASG12C mutation and histologically confirmed PD-L1 TPS \< 50% AND previously completed 4 cycles of standard-of-care platinum based induction chemotherapy with pembrolizumab AND experienced stable disease, partial response, or complete response per investigator's assessment after 4 cycles OR if patients received \<4 cycles of a platinum-based induction, was stopped early due to intolerable toxicity * Cohort E: Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (non-squamous only) KRASG12C mutation and histologically confirmed PD-L1 TPS \< 50% * Presence of measurable disease per RECIST v1.1
Exclusion criteria
* All Cohorts: Any prior therapy targeting KRASG12C mutation in any setting * Cohorts A & E: Prior systemic therapy for locally advanced or metastatic NSCLC, including chemotherapy, immune checkpoint inhibitor therapy or chemoimmunotherapy (note: prior systemic therapy or chemoradiation given in the adjuvant or neoadjuvant setting are allowed if last dose of prior systemic treatment was \>1 year prior to first dose of study treatment) * Cohort C: received maintenance therapy (e.g, pembrolizumab and/or pemetrexed following completion of 4-6 cycles of a platinum-based regimen administered in the first-line setting * Radiation to the lung \> 30 Gy within 6 months prior to first dose of study treatment * Active brain metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) for Cohort A and E | 30 months | Defined as the percent of patients documented to have a confirmed CR or PR |
| Progression-free Survival (PFS) at six months for Cohort C | 30 months | PFS is defined as time from first study treatment until disease progression or death from any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 30 months | Defined as time from date of first study treatment to date of death due to any cause |
| Progression-free Survival (PFS) | 30 months | Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first. |
| Adverse Events | 30 months | Defined as number of patients with treatment emergent AEs |
| Cohorts C and E: DLTs during SLI (Safety Lead In) | 30 months | Defined as those patients in the SLI of the study who have received at least 80% of the assigned dose of adagrasib during the first cycle on study, or interrupted or discontinued study treatment during the first cycle due to a DLT. |
| Population pharmacokinetic (PK) Model Derived AUC at Steady State (AUCtau,ss). | Time Frame: Pre-dose and 4-6 hours post dose; up to 6 months | Concentration data from this study will be pooled with other studies and exposure parameters derived using population PK methods. Data for this Outcome Measure will not be reported here since ClinicalTrials.gov is designed to report results from participants enrolled in the study and described in the Participant Flow module. |
| Duration of Response (DOR) | 30 months | Defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either Progression of Disease (PD) or death due to any cause, whichever occurs first. |
Countries
Brazil, Chile, France, Georgia, Greece, Hungary, Italy, Malaysia, Poland, Serbia, Spain, Switzerland, Thailand, United States
Contacts
Primary ContactBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
Backup ContactFirst line of the email MUST contain the NCT# and Site #.
Outcome results
None listed