Combination Therapies With Adagrasib in Patients With Advanced NSCLC With KRAS G12C Mutation

Metastatic Lung Cancer Clinical Trial

Official title:

A Phase 2 Trial of Combination Therapies With Adagrasib in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05609578
• Other study ID #: CA239-0010
• Secondary ID: 849-017CA239-001
• Status: Recruiting
• Phase: Phase 2
• Start date: November 28, 2022
• Est. completion date: December 1, 2026

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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 1, 2026
• Est. primary completion date: June 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced NSCLC
• Lung Neoplasms
• Metastatic Lung Cancer

Intervention

Drug:
• Adagrasib oral dose of 400 mg twice daily tablets
oral dose of 400 mg twice daily tablets

Combination Product:
• Pembrolizumab
IV infusion once every 3 weeks
• Chemotherapy: Pemetrexed
IV infusion once every 3 weeks
• Cisplatin/Carboplatin
IV infusion once every 3 weeks

Locations

Country	Name	City	State
Brazil	Local Institution - 017-457	Barretos
Brazil	Local Institution - 017-442	Curitiba
Brazil	Local Institution - 017-452	Fortaleza
Brazil	Local Institution - 017-446	Ijui	Rio Grande Do Sul
Brazil	Local Institution - 017-453	Itajai	Santa Catarina
Brazil	Local Institution - 017-455	Jau
Brazil	Local Institution - 017-458	Natal	Rio Grande Do Norte
Brazil	Local Institution - 017-454	Rio De Janeiro
Brazil	Local Institution - 017-456	Sao Paolo
Chile	Local Institution - 017-697	Providencia
Chile	Local Institution - 017-696	Santiago
Chile	Local Institution - 017-698	Temuco
Chile	Local Institution - 017-695	Vina Del Mar	Valparaiso
France	Institut de Cancerologie de lOuest - Angers	Angers Cedex 02
France	Centre Francois Baclesse	Caen Cedex 5
France	Centre Hospitalier Intercommunal de Creteil	Creteil
France	Centre Georges Francois Leclerc	Dijon cedex
France	Hopital Michallon	La Tronche
France	Local Institution - 017-688	Lille
France	Local Institution - Unk078	Lyon
France	Institut Paoli-Calmettes	Marseille
France	Local Institution - Unk067	Marseille
France	Local Institution - 017-200	Montpellier
France	Hopital Tenon	Paris
France	Local Institution - Unk029	Paris
France	Local Institution - 017-664	Paris cedex 05
France	Local Institution - 017-198	Saint Herblain
France	Hopital Foch	Suresnes
France	Hopital Larrey	Toulouse cedex 9
France	Gustave Roussy	Villejuif
Georgia	Local Institution - 017-790	Batumi
Georgia	Local Institution - 017-789	Tbilisi
Georgia	Local Institution - 017-791	Tbilisi
Georgia	Local Institution - 017-792	Tbilisi
Georgia	Local Institution - 017-793	Tbilisi
Georgia	Local Institution - 017-794	Tbilisi
Greece	University General Hospital of Heraklion (PAGNI)	Heraklion
Greece	University General Hospital of Larissa	Larissa
Greece	Metropolitan Hospital	Peiraias
Hungary	Orszagos Koranyi Pulmonologiai Intezet	Budapest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Fejer Varmegyei Szent Gyorgy Egyetemi Oktato Korhaz	Szekesfehervar
Hungary	Reformatus Pulmonologiai Centrum	Torokbalint
Italy	Azienda Ospedaliera San Giuseppe Moscati - Avellino	Avellino
Italy	Local Institution - 017-274	Aviano
Italy	Ospedale Santo Spirito	Casale Monferrato
Italy	Azienda Ospedaliero - Universitaria Careggi	Firenze
Italy	Local Institution - 017-278	Milan
Italy	Azienda Ospedaliero - Universitaria San Luigi Gonzaga	Orbassano
Italy	Local Institution - 017-297	Padova
Italy	Ospedale Santa Maria delle Croci di Ravenna	Ravenna
Italy	Istituto Nazionale Tumori Regina Elena	Roma
Italy	Local Institution - 017-280	Roma
Malaysia	Local Institution - 017-076	Kota Bharu	Kelantan
Malaysia	Local Institution - 017-073	Kuala Lumpur
Malaysia	Local Institution - 017-075	Kuantan	Pahang
Malaysia	Local Institution - 017-072	Putrajaya
Poland	Local Institution - 017-381	Konin
Poland	Instytut MSF	Lodz
Poland	Med Polonia Sp. z o. o. - Obornicka	Poznan
Poland	Wojskowy Instytut Medyczny	Warsaw
Serbia	Local Institution - 017-690	Belgrade
Serbia	Local Institution - 017-692	Belgrade
Serbia	Local Institution - 017-693	Beograd
Serbia	Local Institution - 017-694	Kragujevac
Serbia	Local Institution - 017-691	Sremska Kamenica
Spain	Complejo Hospitalario Universitario A Coruna	A Coruna
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda
Spain	Local Institution - Unk001	Malaga
Spain	Hospital Son Llatzer	Palma de Mallorca
Spain	Hospital Universitario Son Espases	Palma de Mallorca
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Switzerland	Local Institution - 017-395	Geneve
Thailand	Local Institution - 017-132	Bang Phlat
Thailand	Local Institution - 017-136	Bangkok
Thailand	Local Institution - 017-135	Chom Thong
Thailand	Local Institution - 017-137	Khon Kaen
United States	Local Institution - Unk047	Anaheim	California
United States	Local Institution - Unk025	Anchorage	Alaska
United States	Local Institution - Unk009	Baltimore	Maryland
United States	PeaceHealth St. Joseph Medical Center	Bellingham	Washington
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Local Institution - 017-945	Bronx	New York
United States	Local Institution - Unk039	Burlington	Massachusetts
United States	Local Institution - 017-972	Chicago	Illinois
United States	Local Institution - Unk062	Chicago	Illinois
United States	Cleveland Clinic Main Campus	Cleveland	Ohio
United States	Local Institution - Unk056	Dallas	Texas
United States	Texas Oncology - Dallas Fort Worth (DFW) - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Henry Ford Medical Center - Columbus	Detroit	Michigan
United States	Local Institution - Unk069	Detroit	Michigan
United States	Hematology-Oncology Associates of Central New York - Brittonfield - East Syracuse	East Syracuse	New York
United States	Local Institution - Unk066	Fairfax	Virginia
United States	Virginia Cancer Specialists - Fairfax Office	Fairfax	Virginia
United States	MemorialCare - Orange Coast Medical Center	Fountain Valley	California
United States	Providence Medical Foundation - Virginia K. Crosson Cancer Center - Fullerton	Fullerton	California
United States	Local Institution - 017-591	Glendale	Arizona
United States	Local Institution - 017-848	Houston	Texas
United States	Local Institution - Unk036	Huntington	West Virginia
United States	Local Institution - 017-999	Irving	Texas
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Local Institution - 017-836	Kettering	Ohio
United States	The Oncology Institute of Hope and Innovation - Lakeland	Lakeland	Florida
United States	Local Institution - Unk018	Lansing	Michigan
United States	Local Institution - 017-965	Lexington	Kentucky
United States	Local Institution - Unk004	Loma Linda	California
United States	USOR - Rocky Mountain Cancer Centers - Lone Tree	Lone Tree	Colorado
United States	USOR - Texas Oncology Northeast Texas - Longview Cancer Center	Longview	Texas
United States	Local Institution - 017-961	Los Angeles	California
United States	Local Institution - 017-916	Memphis	Tennessee
United States	Local Institution - Unk076	Miami	Florida
United States	Local Institution - Unk055	Orlando	Florida
United States	Local Institution - Unk008	Osage Beach	Missouri
United States	Local Institution - 017-821	Phoenix	Arizona
United States	New York Cancer & Blood Specialists - Cancer Center - Research Headquarters	Port Jefferson Station	New York
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Metro-Minnesota Community Oncology Research Consortium (MMCORC)	Saint Louis Park	Minnesota
United States	Local Institution - Unk010	Salt Lake City	Utah
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Local Institution - Unk058	Springfield	Missouri
United States	University of Kansas Cancer Center - Westwood/Richard and Annette Bloch Cancer Care Pavilion	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Brazil,  Chile,  France,  Georgia,  Greece,  Hungary,  Italy,  Malaysia,  Poland,  Serbia,  Spain,  Switzerland,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) for Cohort A and E	Defined as the percent of patients documented to have a confirmed CR or PR	30 months
Primary	Progression-free Survival (PFS) at six months for Cohort C	PFS is defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.	30 months
Secondary	Adverse Events	Defined as number of patients with treatment emergent AEs	30 months
Secondary	Duration of Response (DOR)	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.	30 months
Secondary	Overall Survival (OS)	Defined as time from date of first study treatment to date of death due to any cause	30 months
Secondary	Progression-free Survival (PFS)	Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.	30 months
Secondary	Population pharmacokinetic (PK) Model Derived AUC at Steady State (AUCtau,ss).	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.	Time Frame: Pre-dose and 4-6 hours post dose; up to 6 months
Secondary	Cohorts C and E: DLTs during SLI (Safety Lead In)	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.	30 months

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting