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 #: CA239-0012
• Secondary ID: 2023-503523-25CA
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2024
• Est. completion date: September 30, 2025

Study information

• Verified date: June 2024
• Source: Mirati Therapeutics Inc.
• Contact: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
• Phone: 855-907-3286
• Email: Clinical.Trials[@]bms.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:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: September 30, 2025
• Est. primary completion date: March 31, 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
Brazil	Local Institution - 178	Belo Horizonte	Minas Gerais
Brazil	Local Institution - 179	Cachoeiro Do Itapemirim	Espírito Santo
Brazil	Local Institution - 182	Itajaí	Santa Catarina
Brazil	Local Institution - 177	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution - 181	Salvador
Brazil	Local Institution - 175	São Paulo
Croatia	Local Institution - 525	Pula
Croatia	Local Institution - 527	Zagreb	Grad Zagreb
France	Local Institution - 554	Angers	Maine-et-Loire
France	Local Institution - 559	Grenoble	Rhône-Alpes
France	Centre Hôspitalier de Bretagne Sud - Hôpital du Scorff	Lorient
France	APHM Hopital Nord	Marseille
France	Local Institution - 555	Nantes cedex 1
France	Hopital Haut-Leveque - Maladies respiratoires	Pessac	Gironde
France	Local Institution - 557	Poitiers	Poitou-Charentes
France	Local Institution - 558	Quimper
France	Local Institution - 553	Saint-Herblain Cedex	Loire-Atlantique
France	Hôpital Bégin - Service d'Oncologie	Saint-Mandé
France	Local Institution - 560	Villefranche Sur Saone	Rhône
Greece	Local Institution - 575	Athens	Attiki
Greece	Local Institution - 582	Athens	Attiki
Greece	Local Institution - 579	Haidari - Athens	Attiki
Greece	Local Institution - 580	Panorama
Greece	Local Institution - 577	Patras	Achaïa
Greece	Local Institution - 576	Thessaloniki	Kentriki Makedonia
Greece	Local Institution - 581	Thessaloniki
Israel	Local Institution - 627	Haifa
Israel	Local Institution - 629	Haifa
Israel	Local Institution - 625	Jerusalem	Yerushalayim
Israel	Local Institution - 628	Tel Aviv-Yafo	Tel-Aviv
Israel	Local Institution - 626	Tel-Aviv
Italy	Local Institution - 780	Candiolo	Torino
Italy	Local Institution - 779	Milano
Italy	Local Institution - 777	Novara
Italy	Local Institution - 775	Perugia
Italy	Local Institution - 778	Pesaro	Pesaro E Urbino
Italy	Local Institution - 776	Roma
Korea, Republic of	National Cancer Center	Gyeonggido [Kyonggi-do]	Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Korea, Republic of	Korea University Guro Hospital	Seoul	Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Korea, Republic of	Samsung Medical Center	Seoul	Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Korea, Republic of	Local Institution - 328	Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Mexico	Local Institution - 129	Cdmx	Distrito Federal
Mexico	Local Institution - 127	Col. Roma	Distrito Federal
Mexico	Local Institution - 125	Toluca
Mexico	Local Institution - 128	Tuxtla Gutiérrez	Chiapas
Netherlands	Local Institution - 800	Amsterdam	Noord-Holland
Netherlands	Local Institution - 802	Breda	Noord-Brabant
Netherlands	Local Institution - 801	Nieuwegein	Utrecht
Poland	Local Institution - 651	Gdynia	Pomorskie
Poland	Local Institution - 650	Krakow	Malopolskie
Poland	Local Institution - 653	Lublin
Romania	Local Institution - 732	Cluj-Napoca	Cluj
Romania	Local Institution - 729	Craiova	Dolj
Romania	Local Institution - 734	Craiova	Dolj
Romania	Local Institution - 733	Iasi
Romania	Local Institution - 731	Ovidiu	Constanta
Romania	Local Institution - 725	Sibiu
Romania	Local Institution - 728	Suceava
Romania	Local Institution - 730	Timisoara	Timis
Serbia	Local Institution - 753	Belgrade	Beograd
Serbia	Local Institution - 752	Kragujevac	Šumadijski Okrug
Serbia	Local Institution - 754	Nis	Niaavski Okrug
Spain	Local Institution - 681	Barcelona
Spain	Local Institution - 683	Barcelona
Spain	Local Institution - 687	Barcelona
Spain	Local Institution - 675	Madrid
Spain	Local Institution - 679	Madrid
Spain	Local Institution - 678	Malaga	Andalucía
Spain	Local Institution - 676	Oviedo	Asturias
Spain	Local Institution - 685	Palma de Mallorca	Baleares
Spain	Complexo Hospitalario Universitario De Santiago	Santiago De Compostela	A Coruña
Spain	Hospital Universitario Virgen De La Macarena	Sevilla
Spain	Local Institution - 677	Valencia
Spain	Local Institution - 684	Valencia	Valenciana, Comunidad
Taiwan	Local Institution - 352	Kaohsuing City	Kaohsiung
Taiwan	China Medical University Hospital - Internal Medicine	Taichung City	Taichung Municipality
Taiwan	Local Institution - 353	Taichung City	Taichung
Taiwan	Local Institution - 355	Taichung City	Taichung
Thailand	Local Institution - 377	Bangkok	Krung Thep Maha Nakhon [Bangkok]
Thailand	Local Institution - 376	Chiang Mai
Thailand	Local Institution - 375	Khon Kaen
Thailand	Local Institution - 378	Songkhla
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	Local Institution - 706	Ankara
Turkey	Memorial Ankara Hastanesi Tibbi Onkoloji	Ankara
Turkey	Trakya Univ Hastanesi Ic Hastal	Edirne
Turkey	Istanbul Onkoloji Hastanesi Tibbi Onkoloji	Istanbul
Turkey	Local Institution - 709	Istanbul
Turkey	Prof. Dr. Suleyman Yalcin Sehir Hastanesi	Istanbul
Turkey	Local Institution - 708	Izmir
United States	Local Institution - 106	Chicago	Illinois
United States	VA North Texas Healthcare System/Dallas VA Medical Center	Dallas	Texas
United States	Veterans Affairs Medical Center (VAMC) - Durham	Durham	North Carolina
United States	Local Institution - 105	Kansas City	Missouri
United States	Local Institution - 103	Minneapolis	Minnesota
United States	Providence Medical Foundation	Santa Rosa	California

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Brazil,  Croatia,  France,  Greece,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Romania,  Serbia,  Spain,  Taiwan,  Thailand,  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

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting