Clinical trial NCT05609578: Combination Therapies With Adagrasib in Patients With Advanced NSCLC With KRAS G12C Mutation
Official title: A Phase 2 Trial of Combination Therapies With Adagrasib in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced NSCLC
Metastatic Lung Cancer
Keywords: KRAS G12C
NSCLC
Non Small Cell Lung Cancer
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-08
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR) for Cohort A and E
timeFrame: 30 months
measure: Progression-free Survival (PFS) at six months for Cohort C
timeFrame: 30 months
Secondary outcomes:
measure: Adverse Events
timeFrame: 30 months
measure: Duration of Response (DOR)
timeFrame: 30 months
measure: Overall Survival (OS)
timeFrame: 30 months
measure: Progression-free Survival (PFS)
timeFrame: 30 months
measure: Population pharmacokinetic (PK) Model Derived AUC at Steady State (AUCtau,ss).
timeFrame: Time Frame: Pre-dose and 4-6 hours post dose; up to 6 months
measure: Cohorts C and E: DLTs during SLI (Safety Lead In)
timeFrame: 30 months
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Local Institution - Unk025
state: Alaska
city: Glendale
country: United States
facility: Local Institution - 017-591
state: Arizona
city: Phoenix
country: United States
facility: Local Institution - 017-821
state: Arizona
city: Anaheim
country: United States
facility: Local Institution - Unk047
state: California
city: Fountain Valley
country: United States
facility: Local Institution - 017-936C
state: California
city: Fountain Valley
country: United States
facility: MemorialCare - Orange Coast Medical Center
state: California
city: Fullerton
country: United States
facility: Providence Medical Foundation - Virginia K. Crosson Cancer Center - Fullerton
state: California
city: Loma Linda
country: United States
facility: Local Institution - Unk004
state: California
city: Los Angeles
country: United States
facility: Local Institution - 017-961
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Local Institution - 017-872-I
state: Colorado
city: Boulder
country: United States
facility: Local Institution - 017-872-G
state: Colorado
city: Colorado Springs
country: United States
facility: Local Institution - 017-872-D
state: Colorado
city: Colorado Springs
country: United States
facility: Local Institution - 017-872-J
state: Colorado
city: Denver
country: United States
facility: Local Institution - 017-872-B
state: Colorado
city: Denver
country: United States
facility: Local Institution - 017-872-F
state: Colorado
city: Lakewood
country: United States
facility: Local Institution - 017-872-A
state: Colorado
city: Littleton
country: United States
facility: Local Institution - 017-872-C
state: Colorado
city: Lone Tree
country: United States
facility: USOR - Rocky Mountain Cancer Centers - Lone Tree
state: Colorado
city: Pueblo
country: United States
facility: Local Institution - 017-872-E
state: Colorado
city: Thornton
country: United States
facility: Local Institution - 017-872-H
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Lakeland
country: United States
facility: The Oncology Institute of Hope and Innovation - Lakeland
state: Florida
city: Miami
country: United States
facility: Local Institution - Unk076
state: Florida
city: Orlando
country: United States
facility: Local Institution - Unk055
state: Florida
city: Chicago
country: United States
facility: Local Institution - Unk062
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Fairway
country: United States
facility: Local Institution - 017-820J
state: Kansas
city: Kansas City
country: United States
facility: Local Institution - 017-820A
state: Kansas
city: Kansas City
country: United States
facility: Local Institution - 017-820B
state: Kansas
city: Kansas City
country: United States
facility: Local Institution - 017-820C
state: Kansas
city: Kansas City
country: United States
facility: Local Institution - 017-820H
state: Kansas
city: Overland Park
country: United States
facility: Local Institution - 017-820I
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Cancer Center - Westwood/Richard and Annette Bloch Cancer Care Pavilion
state: Kansas
city: Lexington
country: United States
facility: Local Institution - 017-965
state: Kentucky
city: Baltimore
country: United States
facility: Local Institution - Unk009
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Burlington
country: United States
facility: Local Institution - Unk039
state: Massachusetts
city: Detroit
country: United States
facility: Local Institution - Unk069
state: Michigan
city: Lansing
country: United States
facility: Local Institution - Unk018
state: Michigan
city: Novi
country: United States
facility: Henry Ford Medical Center - Columbus
state: Michigan
city: Minneapolis
country: United States
facility: Local Institution - 017-838B
state: Minnesota
city: Minneapolis
country: United States
facility: Local Institution - 017-838C
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro-Minnesota Community Oncology Research Consortium (MMCORC)
state: Minnesota
city: Saint Louis Park
country: United States
facility: Local Institution - 017-838A
state: Minnesota
city: Kansas City
country: United States
facility: Local Institution - 017-820F
state: Missouri
city: Kansas City
country: United States
facility: Local Institution - 017-820E
state: Missouri
city: Lee's Summit
country: United States
facility: Local Institution - 017-820D
state: Missouri
city: North Kansas City
country: United States
facility: Local Institution - 017-820G
state: Missouri
city: Osage Beach
country: United States
facility: Local Institution - Unk008
state: Missouri
city: Springfield
country: United States
facility: Local Institution - Unk058
state: Missouri
city: Babylon
country: United States
facility: Local Institution - 017-080
state: New York
city: Bronx
country: United States
facility: Local Institution - 017-945
state: New York
city: Bronx
country: United States
facility: Local Institution - 017-083
state: New York
city: Brooklyn
country: United States
facility: Local Institution - 017-088
state: New York
city: East Syracuse
country: United States
facility: Hematology-Oncology Associates of Central New York - Brittonfield - East Syracuse
state: New York
city: New Hyde Park
country: United States
facility: Local Institution - 017-087
state: New York
city: New York
country: United States
facility: Local Institution - 017-085
state: New York
city: Patchogue
country: United States
facility: Local Institution - 017-082
state: New York
city: Port Jefferson Station
country: United States
facility: Local Institution - 017-081
state: New York
city: Port Jefferson Station
country: United States
facility: New York Cancer & Blood Specialists - Cancer Center - Research Headquarters
state: New York
city: Port Jefferson
country: United States
facility: Local Institution - 017-086
state: New York
city: Riverhead
country: United States
facility: Local Institution - 017-084
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus
state: Ohio
city: Kettering
country: United States
facility: Local Institution - 017-836
state: Ohio
city: Memphis
country: United States
facility: Local Institution - 017-916
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - Dallas Fort Worth (DFW) - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: Local Institution - Unk056
state: Texas
city: Houston
country: United States
facility: Local Institution - 017-848
state: Texas
city: Irving
country: United States
facility: Local Institution - 017-999
state: Texas
city: Longview
country: United States
facility: USOR - Texas Oncology Northeast Texas - Longview Cancer Center
state: Texas
city: Palestine
country: United States
facility: Local Institution - 017-878-B
state: Texas
city: Paris
country: United States
facility: Local Institution - 017-878-C
state: Texas
city: Tyler
country: United States
facility: Local Institution - 017-878-A
state: Texas
city: Salt Lake City
country: United States
facility: Local Institution - Unk010
state: Utah
city: Arlington
country: United States
facility: Local Institution - 017-814-A
state: Virginia
city: Fairfax
country: United States
facility: Local Institution - Unk066
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists - Fairfax Office
state: Virginia
city: Gainesville
country: United States
facility: Local Institution - 017-814-B
state: Virginia
city: Reston
country: United States
facility: Local Institution - 017-814-C
state: Virginia
city: Bellingham
country: United States
facility: PeaceHealth St. Joseph Medical Center
state: Washington
city: Huntington
country: United States
facility: Local Institution - Unk036
state: West Virginia
city: Natal
country: Brazil
facility: Local Institution - 017-458
state: Rio Grande Do Norte
city: Ijui
country: Brazil
facility: Local Institution - 017-446
state: Rio Grande Do Sul
city: Itajai
country: Brazil
facility: Local Institution - 017-453
state: Santa Catarina
city: Barretos
country: Brazil
facility: Local Institution - 017-457
city: Curitiba
country: Brazil
facility: Local Institution - 017-442
city: Fortaleza
country: Brazil
facility: Local Institution - 017-452
city: Jau
country: Brazil
facility: Local Institution - 017-455
city: Rio De Janeiro
country: Brazil
facility: Local Institution - 017-454
city: Sao Paolo
country: Brazil
facility: Local Institution - 017-456
city: Vina Del Mar
country: Chile
facility: Local Institution - 017-695
state: Valparaiso
city: Providencia
country: Chile
facility: Local Institution - 017-697
city: Santiago
country: Chile
facility: Local Institution - 017-696
city: Temuco
country: Chile
facility: Local Institution - 017-698
city: Angers Cedex 02
country: France
facility: Institut de Cancerologie de lOuest - Angers
city: Caen Cedex 5
country: France
facility: Centre Francois Baclesse
city: Creteil
country: France
facility: Centre Hospitalier Intercommunal de Creteil
city: Dijon cedex
country: France
facility: Centre Georges Francois Leclerc
city: La Tronche
country: France
facility: Hopital Michallon
city: Lille
country: France
facility: Local Institution - 017-688
city: Lyon
country: France
facility: Local Institution - Unk078
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Marseille
country: France
facility: Local Institution - Unk067
city: Montpellier
country: France
facility: Local Institution - 017-200
city: Paris cedex 05
country: France
facility: Local Institution - 017-664
city: Paris
country: France
facility: Local Institution - Unk029
city: Paris
country: France
facility: Hopital Tenon
city: Saint Herblain
country: France
facility: Local Institution - 017-198
city: Suresnes
country: France
facility: Hopital Foch
city: Toulouse cedex 9
country: France
facility: Hopital Larrey
city: Villejuif
country: France
facility: Gustave Roussy
city: Batumi
country: Georgia
facility: Local Institution - 017-790
city: Tbilisi
country: Georgia
facility: Local Institution - 017-789
city: Tbilisi
country: Georgia
facility: Local Institution - 017-794
city: Tbilisi
country: Georgia
facility: Local Institution - 017-791
city: Tbilisi
country: Georgia
facility: Local Institution - 017-792
city: Tbilisi
country: Georgia
facility: Local Institution - 017-793
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion (PAGNI)
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Peiraias
country: Greece
facility: Metropolitan Hospital
city: Budapest
country: Hungary
facility: Orszagos Koranyi Pulmonologiai Intezet
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Szekesfehervar
country: Hungary
facility: Fejer Varmegyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Torokbalint
country: Hungary
facility: Reformatus Pulmonologiai Centrum
city: Faenza
country: Italy
facility: Local Institution - 017-767 - B
state: Ravenna
city: Lugo
country: Italy
facility: Local Institution - 017-767 - A
state: Ravenna
city: Avellino
country: Italy
facility: Azienda Ospedaliera San Giuseppe Moscati - Avellino
city: Aviano
country: Italy
facility: Local Institution - 017-274
city: Casale Monferrato
country: Italy
facility: Ospedale Santo Spirito
city: Firenze
country: Italy
facility: Azienda Ospedaliero - Universitaria Careggi
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
city: Orbassano
country: Italy
facility: Azienda Ospedaliero - Universitaria San Luigi Gonzaga
city: Padova
country: Italy
facility: Local Institution - 017-297
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci di Ravenna
city: Roma
country: Italy
facility: IRCCS Istituto Nazionale Tumori Regina Elena
city: Roma
country: Italy
facility: Local Institution - 017-280
city: Kota Bharu
country: Malaysia
facility: Local Institution - 017-076
state: Kelantan
city: Kuantan
country: Malaysia
facility: Local Institution - 017-075
state: Pahang
city: Kuala Lumpur
country: Malaysia
facility: Local Institution - 017-073
city: Putrajaya
country: Malaysia
facility: Local Institution - 017-072
city: Konin
country: Poland
facility: Local Institution - 017-381
city: Lodz
country: Poland
facility: Instytut MSF
city: Poznan
country: Poland
facility: Med Polonia Sp. z o. o. - Obornicka
city: Warsaw
country: Poland
facility: Wojskowy Instytut Medyczny
city: Belgrade
country: Serbia
facility: Local Institution - 017-692
city: Belgrade
country: Serbia
facility: Local Institution - 017-690
city: Beograd
country: Serbia
facility: Local Institution - 017-693
city: Kragujevac
country: Serbia
facility: Local Institution - 017-694
city: Sremska Kamenica
country: Serbia
facility: Local Institution - 017-691
city: A Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruna
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
city: Malaga
country: Spain
facility: Local Institution - Unk001
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Espases
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Geneve
country: Switzerland
facility: Local Institution - 017-395
city: Bang Phlat
country: Thailand
facility: Local Institution - 017-132
city: Bangkok
country: Thailand
facility: Local Institution - 017-136
city: Chom Thong
country: Thailand
facility: Local Institution - 017-135
city: Khon Kaen
country: Thailand
facility: Local Institution - 017-137
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: