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 #: 849-017
• Status: Recruiting
• Phase: Phase 2
• Start date: July 29, 2022
• Est. completion date: December 1, 2026

Study information

• Verified date: April 2024
• Source: Mirati Therapeutics Inc.
• Contact: Mirati Therapeutics Study Locator Services
• Phone: 18448935530
• Email: miratistudylocator[@]careboxhealth.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study 849-017 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
France	Institut de Cancérologie de l'Ouest - Angers - Site Paul Papin	Angers
France	Centre François Baclesse	Caen Cedex 05	Basse-Normadie
France	Centre Hospitalier Intercommunal de Créteil	Créteil	Ile-De-France
France	Centre Georges François Leclerc	Dijon Cedex	Bourgogne
France	Hôpital Michallon	La Tronche	Rhone
France	Institut Paoli-Calmettes	Marseille
France	Hôpital Tenon	Paris
France	Hôpital Foch	Suresnes	Île-de-France
France	Hôpital Larrey	Toulouse Cedex 9	Midi-Pyrenees
France	Gustave Roussy	Villejuif
Greece	University General Hospital of Heraklion (PAGNI)	Heraklion	Crete
Greece	University General Hospital of Larissa	Larissa	Thessaly
Greece	Metropolitan Hospital	Piraeus	Attica
Hungary	Országos Korányi Pulmonológiai Intézet	Budapest
Hungary	Országos Onkológiai Intézet	Budapest
Hungary	Tüdogyógyintézet Törökbálint	Torokbalint
Italy	Azienda Ospedaliera San Giuseppe Moscati - Avellino	Avellino
Italy	Ospedale Santo Spirito	Casale Monferrato	Alessandria
Italy	Azienda Ospedaliero - Universitaria Careggi	Firenze	Florence
Italy	Azienda Ospedaliero - Universitaria San Luigi Gonzaga	Orbassano
Italy	Ospedale Santa Maria delle Croci di Ravenna	Ravenna
Italy	Istituto Nazionale Tumori Regina Elena	Rome
Poland	Instytut MSF	Lódz
Poland	Med Polonia Sp. z o. o. - Obornicka	Poznan
Poland	Wojskowy Instytut Medyczny	Warsaw
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro De Majadahonda	Majadahonda	Madrid
Spain	Hospital Son Llàtzer	Palma De Mallorca
Spain	Hospital Universitario Son Espases	Palma De Mallorca	Balearic Islands
Spain	Hospital Universitario Virgen De La Macarena	Sevilla
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
United States	Texas Oncology Northeast	Austin	Texas
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	MemorialCare - Orange Coast Medical Center	California City	California
United States	Cleveland Clinic	Cleveland	Ohio
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	USOR - Rocky Mountain Cancer Centers - Denver - Rose Medical Center Campus	Denver	Colorado
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	Hematology Oncology Associates of CNY, PC	East Syracuse	New York
United States	NEXT Virginia	Fairfax	Virginia
United States	MemorialCare - OC Blood and Cancer Center	Fountain Valley	California
United States	Providence Medical Foundation - Virginia K. Crosson Cancer Center - Fullerton	Fullerton	California
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	The Oncology Institute of Hope and Innovation	Lakeland	Florida
United States	New York Cancer & Blood Specialists	Port Jefferson Station	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	UKCC - 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,  France,  Greece,  Hungary,  Italy,  Poland,  Spain, 

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