This study will evaluate the efficacy of two dosing regimens of adagrasib (600 mg BID versus 400 mg BID) in patients with NSCLC with KRAS G12C mutation.
CA239-0012 is a phase 2 study of adagrasib monotherapy in which patients are randomized between two dosing regimens. The study will evaluate the efficacy of two dosing regimens of adagrasib (600 mg BID without regard to food versus 400 mg BID with food) in patients with NSCLC with KRAS G12C mutation and who have received prior treatment with a platinum-based regimen and immune checkpoint inhibitor therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
200
KRAS G12C inhibitor
Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
ORR evaluation of subjects treated with adagrasib 600 mg BID without regard to food versus 400 mg BID with food having NSCLC with KRAS G12C mutation (Study Population) will be completed per blinded independent central radiology (BICR) review. Objective response is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from 1st dose of adagrasib until last dose of adagrasib.
Time frame: 30 months
Evaluate Overall Survival (OS).
Overall survival is defined as time from date of randomization to date of death due to any cause.
Time frame: 45 months
Evaluate Progression Free Survival (PFS).
Progression-free survival is defined as time from date of randomization to date of first progression per RECIST 1.1 or death from any cause, whichever occurs first.
Time frame: 30 months
Evaluate Duration of Response (DOR).
Duration of response defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either PD (per BICR review) or death due to any cause, whichever occurs first.
Time frame: 30 months
Safety and tolerability in the study population.
Safety characterized by number of participants with AEs, with abnormal laboratory test results and number of patients modifying or discontinuing study treatment due to an AE: 1. Type, incidence, severity, timing, seriousness, and relationship to study treatment of Adverse Events. 2. Laboratory abnormalities as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment. 3. Number of patients modifying or discontinuing study treatment due to Adverse Event.
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Local Institution - 101
Santa Rosa, California, United States
Local Institution - 105
Kansas City, Missouri, United States
Local Institution - 100
Durham, North Carolina, United States
Local Institution - 106
Dallas, Texas, United States
Local Institution - 181
Salvador, Estado de Bahia, Brazil
Local Institution - 177
Porto Alegre, Rio Grande do Sul, Brazil
Local Institution - 182
Itajaí, Santa Catarina, Brazil
Local Institution - 178
Belo Horizonte, São Paulo, Brazil
Local Institution - 102
São Paulo, Brazil
Local Institution - 175
São Paulo, Brazil
...and 88 more locations
Time frame: 30 months
Population pharmacokinetic (PK) Model Derived Area Under the Curve During the Dosing Interval at Steady State (AUCtau,ss).
Sparse concentration data from this study will be pooled with other studies and analyzed using population PK methods to derive individual exposure parameters. Data for this Outcome Measure will not be reported here since ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Time frame: Pre-dose and 4-6 hours post dose; up to 6 months.
Patient-reported symptoms during adagrasib administration from first dose to 28 days after last dose of adagrasib.
Patient reported outcomes (PROs) will be used to assess symptomatic toxicity of adagrasib using the NCI Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Measurement System. PRO items reflect the specific symptom 1) frequency, severity, interference with usual or daily activities, 2) amount, or 3) presence or absence. PRO-CTCAE responses are scored from 0 (low) to 4 (high), or 0/1 for absent/present, and scores for each attribute (frequency, severity and/or interference) are presented descriptively.
Time frame: 30 months
Patient -reported quality of life during adagrasib administration from first dose to End of Treatment visit.
Patient reported quality of life questionnaire will be used to assess five dimensions of patient health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using the 5-Level EQ-5D version (EQ-5D-5L) established by the EuroQol Group. This is presented descriptively, and patient responses correspond to a value of 1 (low) or 5 (high). Additionally, a one- page Visual Analog Scale (VAS) will be provided to patients so they may report their self-rated health from the best (100) and worst (0) health imaginable.
Time frame: 30 months