Trial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)

Sponsor

Mirati Therapeutics Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05853575

Collaborator

(none)

200

Enrollment

Location

Arms

28.9

Anticipated Duration (Months)

6.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancer Metastatic Cancer Malignant Neoplasm of Lung	Drug: Adagrasib	Phase 2

Detailed Description

849-021 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 Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Study of Two Dosing Regimens of Adagrasib in Patients With Previously Treated Non-Small Cell Lung Cancer With KRAS G12C Mutation

Actual Study Start Date :

Apr 5, 2023

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adagrasib 600mg BID Adagrasib 600mg BID without regard to food	Drug: Adagrasib KRAS G12C inhibitor Other Names: MRTX849 Krazati
Experimental: Adagrasib 400mg BID Adagrasib 400mg BID with food	Drug: Adagrasib KRAS G12C inhibitor Other Names: MRTX849 Krazati

Arm

Intervention/Treatment

Experimental: Adagrasib 600mg BID

Adagrasib 600mg BID without regard to food

Drug: Adagrasib

KRAS G12C inhibitor

Other Names:

MRTX849

Krazati

Experimental: Adagrasib 400mg BID

Adagrasib 400mg BID with food

Drug: Adagrasib

KRAS G12C inhibitor

Other Names:

MRTX849

Krazati

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). [30 months]
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.

Secondary Outcome Measures

Evaluate Overall Survival (OS). [45 months]
Overall survival is defined as time from date of randomization to date of death due to any cause.
Evaluate Progression Free Survival (PFS). [30 months]
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.
Evaluate Duration of Response (DOR). [30 months]
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.
Safety and tolerability in the study population. [30 months]
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: Type, incidence, severity, timing, seriousness, and relationship to study treatment of Adverse Events. Laboratory abnormalities as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment. Number of patients modifying or discontinuing study treatment due to Adverse Event.
Population pharmacokinetic (PK) Model Derived Area Under the Curve During the Dosing Interval at Steady State (AUCtau,ss). [Pre-dose and 4-6 hours post dose; up to 6 months.]
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.
Patient-reported symptoms during adagrasib administration from first dose to 28 days after last dose of adagrasib. [30 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Are at least 18 years old (or old enough to legally make their own treatment decisions, according to local laws).
Have advanced NSCLC or metastatic NSCLC (NSCLC that started in the lungs and then spread to other parts of the body) with the KRAS G12C mutation.
Have had previous treatment with 1) chemotherapy that included a drug called cisplatin or a drug called carboplatin and 2) a type of drug called an immune checkpoint inhibitor.
Have recovered from their prior treatment and blood tests are within a safe range.

Key Exclusion Criteria:

Have had previous treatment with a drug that targets KRAS G12C.
Have cancer that can potentially be removed with surgery.
Patients with active brain metastases are eligible if 1) brain metastases are adequately treated and 2) are neurologically stable for at least 2 weeks prior to randomization.
Steroid dosing > 10 mg daily prednisone (or equivalent).
Have certain medical conditions or need to take certain medications that, in the opinion of a trial doctor, could make it unsafe for them to participate or difficult to complete the trial assessments, or are pregnant.