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

Metastatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05853575
• Other study ID #: 849-021
• Secondary ID: 2023-503523-25
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2024
• Est. completion date: September 2025

Study information

• Verified date: April 2024
• Source: Mirati Therapeutics Inc.
• Contact: Mirati Therapeutics
• Phone: 1-844-893-5530
• Email: miratistudylocator[@]emergingmd.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: September 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 brain lesions are not eligible if 1) any untreated brain lesions are > 2.0 cm in size 2) any brainstem lesions are present 3) ongoing steroid dosing >10 mg daily prednisone (or equivalent) and 4) poorly controlled (> 1/week) generalized or complex partial seizures or neurologic progression/instability due to brain lesions.
• 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.

Related Conditions & MeSH terms

• Advanced Cancer
• Lung Neoplasms
• Malignant Neoplasm of Lung
• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms

Intervention

Drug:
• Adagrasib
KRAS G12C inhibitor

Locations

Country	Name	City	State
France	Centre Hospitalier de Bretagne Sud - Hopital du Scorff	Lorient
France	APHM Hopital Nord	Marseille
France	Hopital Haut-Leveque-Maladies Respiratoires	Pessac
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Samsung Medical Center	Seoul
Spain	Hopital Universitario Virgen De La Macarena	Sevilla
Taiwan	China Medical University Hospital - Internal Medicine	Taichung City
Turkey	Ankara Liv Hospital Tibbi Onkoloji	Ankara
Turkey	Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi	Ankara
Turkey	Gulhane Egitim ve Arastirma Hastanesi tibbi Onkoloji Klinigi	Ankara
Turkey	Memorial Ankara Hastanesi Tibbi Onkoloji	Ankara
Turkey	Trakya Universitesi Hastanesi Ic Hastaliklari Anabilim Dali Tibbi Onkoloji	Edirne
Turkey	Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi Tibbi Onkoloji	Istanbul
Turkey	Istanbul Onkoloji Hastanesi Tibbi Onkoloji	Istanbul
United States	VA North Texas Healthcare System/Dallas VA Medical Center	Dallas	Texas
United States	Durham VA Medical Center	Durham	North Carolina
United States	Providence Medical Foundation	Santa Rosa	California

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Countries where clinical trial is conducted

United States,  France,  Korea, Republic of,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	30 months
Secondary	Evaluate Overall Survival (OS).	Overall survival is defined as time from date of randomization to date of death due to any cause.	45 months
Secondary	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.	30 months
Secondary	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.	30 months
Secondary	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: 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.	30 months
Secondary	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.	Pre-dose and 4-6 hours post dose; up to 6 months.
Secondary	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.	30 months
Secondary	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.	30 months