A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)

Non-Small Cell Lung Cancer (NSCLC) Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Open-label Study Evaluating Efficacy of Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Subjects With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers, Negative for PD-L1, and Positive for KRAS p.G12C (CodeBreaK 202)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05920356
• Other study ID #: 20190341
• Secondary ID: 2022-501863-41
• Status: Recruiting
• Phase: Phase 3
• Start date: November 16, 2023
• Est. completion date: March 1, 2031

Study information

• Verified date: April 2024
• Source: Amgen
• Contact: Amgen Call Center
• Phone: 866-572-6436
• Email: medinfo[@]amgen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to compare progression-free survival (PFS) in participants who receive sotorasib with platinum doublet chemotherapy versus participants who receive pembrolizumab with platinum doublet chemotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: March 1, 2031
• Est. primary completion date: February 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of nonsquamous stage IV or advanced Stage IIIB or IIIC NSCLC with KRAS p. G12C mutation and negative for PD-L1 expression by central testing or local laboratory testing confirmed through central testing
• No history of systemic anticancer therapy in metastatic/non-curable settings
• Eastern Cooperative Oncology Group (ECOG) = 1

Exclusion Criteria:

• Mixed histology NSCLC with either small-cell or large-cell neuroendocrine cell component or predominant squamous cell histology
• Participants with tumors known to harbor molecular alterations for which targeted therapy is locally approved
• Symptomatic (treated or untreated) brain metastases
• Gastrointestinal (GI) tract disease causing the inability to take oral medication
• Myocardial infarction within 6 months of randomization, unstable arrhythmias, or unstable angina
• Prior therapy with a KRAS G12C inhibitor

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• Sotorasib
Oral administration
• Pembrolizumab
Intravenous administration

Locations

Country	Name	City	State
Argentina	Centro Oncologico Korben	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires	Caba	Buenos Aires
Argentina	Instituto Alexander Fleming	Capital Federal	Buenos Aires
Argentina	Instituto Argentino de Diagnostico y Tratamiento IADT	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	Fundacion Centro Oncológico Riojano Integral para la Investigación y Prevención del Cáncer	La Rioja
Argentina	Sanatorio Parque SA	Rosario	Santa Fe
Argentina	Centro de Diagnostico Investigacion y Tratamiento	Salta
Argentina	Fundacion Ars Medica	San Salvador de Jujuy	Jujuy
Argentina	Clinica Viedma	Viedma	Río Negro
Australia	Cancer Research South Australia	Adelaide	South Australia
Australia	Campbelltown Hospital	Campbelltown	New South Wales
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	GenesisCare -North Shore Oncology	St Leonards	New South Wales
Australia	Toowoomba Hospital	Toowoomba	Queensland
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	Medizinische Universitaet Graz	Graz
Austria	Klinikum Klagenfurt am Woerthersee	Klagenfurt
Austria	Universitaetsklinikum Krems	Krems
Austria	Landeskrankenhaus Salzburg	Salzburg
Belgium	Chirec - Delta Ziekenhuis	Auderghem
Belgium	Universitair Ziekenhuis Leuven - Campus Gasthuisberg	Leuven
Belgium	Centre Hospitalier Regional de la Citadelle	Liège
Belgium	Algemeen Ziekenhuis Sint-Maarten	Mechelen
Brazil	Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto de Medicina Integral Professor Fernando Figueira	Recife	Pernambuco
Brazil	Centro de pesquisa em oncologia Hospital Ana Nery	Santa Cruz do Sul	Rio Grande Do Sul
Brazil	Instituto do Cancer do Estado de Sao Paulo Octavio Frias de Oliveira Icesp	São Paulo
Bulgaria	Multiprofile Hospital for Active Treatment - Uni Hospital OOD	Panagyurishte
Bulgaria	Acibadem City Clinic University Multiprofile Hospital for Active Treatment Tokuda EAD	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna - ISUL EAD	Sofia
Canada	Queen Elizabeth II, Health Sciences Centre	Halifax	Nova Scotia
Canada	McGill University Health Centre Glen Site	Montreal	Quebec
Chile	Biocinetic	Santiago
Chile	Fundacion Arturo Lopez Perez	Santiago
Chile	Orlandi Oncologia	Santiago
Chile	Centro de Investigacion del Maule	Talca
Chile	Clinica CIDO	Temuco	Cautín
Chile	James Lind Centro de Investigacion del Cancer	Temuco	Cautín
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Plzen	Plzen
Denmark	Aarhus Universitetshospital	Aarhus N
Denmark	Regionshospitalet Godstrup	Herning
Denmark	Rigshospitalet	Kobenhavn
Denmark	Sonderborg Sygehus	Sonderborg
France	Centre Hospitalier Régional Universitaire de Besançon, Hôpital Jean Minjoz	Besancon cedex
France	Centre Hospitalier Universitaire Ambroise Pare	Boulogne-Billancourt
France	Centre Hospitalier Intercommunal de Créteil	Créteil
France	Centre Hospitalier - Le Mans	Le Mans
France	Centre Hospitalier Régional Universitaire de Lille - Institut Coeur Poumon	Lille Cedex
France	Centre Hospitalier Universitaire Nord	Marseille Cedex 20
France	Centre de Cancerologie du Grand Montpellier-Clinique Clementville	Montpellier
France	Hopital Universitaire Caremeau	Nimes cedex 9
France	Groupe Hospitalier Paris Saint Joseph	Paris
France	Institut Curie	Paris
France	Hôpital Tenon	Paris Cedex 20
France	Centre Hospitalier Universitaire de Bordeaux - Hopital Haut Leveque	Pessac Cedex
France	Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie	Poitiers Cedex
France	Centre Hospitalier de Cornouaille	Quimper
France	Centre Hospitalier Universitaire de Reims - Hôpital Maison blanche	Reims Cedex
France	Hopital d instruction des armees sainte anne	Toulon
France	Centre Hospitalier Universitaire de Toulouse - Hopital Larrey	Toulouse Cedex 9
France	Centre Hospitalier Régional Universitaire de Tours - Hôpital Bretonneau	Tours Cedex 9
France	Hopital Nord-Ouest Villefranche	Villefranche Sur Saone Cedex
Germany	Klinikum Chemnitz GmbH	Chemnitz
Germany	Universitaetsmedizin Goettingen	Goettingen
Germany	Klinikverbund Allgaeu	Kempten
Greece	251 General Airforce Hospital	Athens
Greece	Alexandra Hospital	Athens
Greece	Attikon University Hospital	Athens
Greece	Henry Dunant Hospital Center	Athens
Greece	Metropolitan Hospital	Athens
Greece	Iaso General Clinic	Marousi
Greece	Agios Loukas Clinic	Thessaloniki
Greece	European Interbalkan Medical Center	Thessaloniki
Greece	Theagenion Cancer Hospital	Thessaloniki
Hong Kong	University of Hong Kong, Queen Mary Hospital	Hong Kong
Hungary	Orszagos Koranyi Pulmonologiai Intezet	Budapest
Hungary	Farkasgyepui Tudogyogyintezet	Farkasgyepu
Hungary	Matrai Gyogyintezet	Gyongyos
Hungary	Fejer Varmegyei Szent Gyorgy Egyetemi Oktato Korhaz	Szekesfehervar
Hungary	Komarom-Esztergom Varmegyei Szent Borbala Korhaz	Tatabanya
Hungary	Reformatus Pulmonologiai Centrum	Torokbalint
Italy	IRCCS Istituto Tumori Giovanni Paolo II	Bari
Italy	Azienda Ospedaliero Universitaria Policlinico G Rodolico - San Marco Presidio Ospedaliero G Rodolico	Catania
Italy	Azienda Ospedaliero Universitaria Careggi	Firenze
Italy	Istituto Romagnolo per lo Studio dei Tumori Dino Amadori	Meldola (FC)
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza (MB)
Italy	Azienda Ospedaliera di Rilievo Nazionale Specialistica dei Colli Monaldi	Napoli
Italy	Azienda Ospedaliera di Perugia Ospedale Santa Maria della Misericordia	Perugia
Japan	Juntendo University Hospital	Bunkyo-ku	Tokyo
Japan	Chiba Cancer Center	Chiba-shi	Chiba
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Fukuoka
Japan	Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers	Fukuyama-shi	Hiroshima
Japan	Kansai Medical University Hospital	Hirakata-shi	Osaka
Japan	Hirosaki University Hospital	Hirosaki-shi	Aomori
Japan	Kanazawa University Hospital	Kanazawa-shi	Ishikawa
Japan	National Cancer Center Hospital East	Kashiwa-shi	Chiba
Japan	St Marianna University Hospital	Kawasaki-shi	Kanagawa
Japan	Saitama Cancer Center	Kitaadachi-gun	Saitama
Japan	Hospital of the University of Occupational and Environmental Health Japan	Kitakyushu-shi	Fukuoka
Japan	Kobe Minimally invasive Cancer Center	Kobe-shi	Hyogo
Japan	The Cancer Institute Hospital of Japanese Foundation for Cancer Research	Koto-ku	Tokyo
Japan	Kurume University Hospital	Kurume-shi	Fukuoka
Japan	Kyoto University Hospital	Kyoto-shi	Kyoto
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama-shi	Ehime
Japan	Nagoya University Hospital	Nagoya-shi	Aichi
Japan	Miyagi Cancer Center	Natori-shi	Miyagi
Japan	Niigata Cancer Center Hospital	Niigata-shi	Niigata
Japan	Okayama University Hospital	Okayama-shi	Okayama
Japan	Osaka International Cancer Institute	Osaka-shi	Osaka
Japan	Kindai University Hospital	Osakasayama-shi	Osaka
Japan	National Hospital Organization Kinki-chuo Chest Medical Center	Sakai-shi	Osaka
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo-shi	Hokkaido
Japan	Sendai Kousei Hospital	Sendai-shi	Miyagi
Japan	Shizuoka Cancer Center	Sunto-gun	Shizuoka
Japan	Takarazuka City Hospital	Takarazuka-shi	Hyogo
Japan	National Hospital Organization Yamaguchi-Ube Medical Center	Ube-shi	Yamaguchi
Japan	Wakayama Medical University Hospital	Wakayama-shi	Wakayama
Japan	Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center	Yokohama-shi	Kanagawa
Japan	Tottori University Hospital	Yonago-shi	Tottori
Korea, Republic of	National Cancer Center	Goyang-si Gyeonggi-do
Korea, Republic of	Gachon University Gil Hospital	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Latvia	Pauls Stradins Clinical University Hospital	Riga
Latvia	Riga East Clinical University Hospital	Riga
Malaysia	University Malaya Medical Centre	Kuala Lumpur	Wilayah Persekutuan
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Sint Jansdal Ziekenhuis	Harderwijk
Netherlands	Maastricht Universitair Medisch Centrum	Maastricht
Netherlands	Elisabeth-TweeSteden Ziekenhuis	Tilburg
Netherlands	Isala Klinieken	Zwolle
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok
Poland	Centrum Pulmonologii i Torakochirurgii w Bystrej	Bystra
Poland	Szpital Specjalistyczny imienia Ludwika Rydygiera w Krakowie Sp zoo	Krakow
Poland	Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie	Lublin
Poland	Med Polonia Sp zoo	Poznan
Poland	Wojewodzki Szpital im Sw Ojca Pio w Przemyslu	Przemysl
Poland	Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warszawa
Portugal	Fundacao Champalimaud	Lisboa
Portugal	Hospital Cuf Tejo	Lisboa
Portugal	Hospital da Luz, SA	Lisboa
Portugal	Unidade Local de Saude de Santa Maria, EPE - Hospital Pulido Valente	Lisboa
Portugal	Unidade Local de Saude de Matosinhos, EPE - Hospital Pedro Hispano	Matosinhos
Portugal	Hospital Cuf porto	Porto
Romania	Institutul Oncologic, Prof Dr Alexandru Trestioreanu	Bucuresti
Romania	Spitalul Universitar de Urgenta Bucuresti	Bucuresti
Romania	Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca	Cluj Napoca
Romania	SC Medisprof SRL	Cluj Napoca
Romania	Centrul de Oncologie Sf Nectarie SRL	Craiova
Romania	Institutul Regional de Oncologie Iasi	Iasi
Romania	Spitalul Municipal Ploiesti	Ploiesti
Romania	SC Oncomed SRL	Timisoara
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona	Cataluña
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Cataluña
Spain	Hospital del Mar	Barcelona	Cataluña
Spain	Hospital Universitari Vall d Hebron	Barcelona	Cataluña
Spain	Institut Catala d Oncologia Hospitalet Hospital Duran i Reynals	Hospitalet de Llobregat	Cataluña
Spain	Hospital Universitario Insular de Gran Canaria	Las Palmas de Gran Canaria	Canarias
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario Virgen del Rocio	Sevilla	Andalucía
Spain	Hospital Clinico Universitario de Valencia	Valencia	Comunidad Valenciana
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza	Aragón
Sweden	Gavle Sjukhus	Gävle
Sweden	Sahlgrenska Universitetssjukhuset	Goteborg
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Kantonsspital Baden	Baden
Switzerland	Universitaetsspital Basel	Basel
Taiwan	Veterans General Hospital - Taichung	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan
Thailand	Phramongkutklao Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital	Chiang Mai
Thailand	Srinagarind Hospital	Khon Kaen
Turkey	Ankara Bilkent Sehir Hastanesi	Ankara
Turkey	Pamukkale Universitesi Tip Fakultesi Hastanesi	Denizli
Turkey	Bagcilar Medipol Mega Universite Hastanesi	Istanbul
Turkey	Goztepe Prof Dr Suleyman Yalcin Sehir Hastanesi	Istanbul
Turkey	Istanbul Universitesi Cerrahpasa Tip Fakultesi	Istanbul
Turkey	Izmir Ekonomi Universitesi Medical Point Hastanesi	Izmir
United Kingdom	Raigmore Hospital	Inverness
United Kingdom	Royal Cornwall Hospital	Truro
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Tennessee Medical Center Knoxville	Knoxville	Tennessee
United States	University of Pittsburgh Medical Center Hillman Cancer Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Czechia,  Denmark,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Italy,  Japan,  Korea, Republic of,  Latvia,  Malaysia,  Netherlands,  Poland,  Portugal,  Romania,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	PFS is defined as the time from randomization until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first. Progression will be based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, per Blinded Independent Central Review (BICR).	From Baseline up to end of study (EOS) (approximately 5.5 years)
Secondary	Objective Response Rate (ORR)	Objective response is defined as the best overall response of complete response (CR) or partial response (PR), based on RECIST v1.1, per BICR.	From Baseline up to EOS (approximately 5.5 years)
Secondary	Overall Survival (OS)	OS is defined as the time from randomization until death due to any cause.	From Baseline up to EOS (approximately 5.5 years)
Secondary	Change in Quality-of-Life Questionnaire Core 30 (QLQ-C30) Dyspnea Domain Score		From Baseline to Week 12
Secondary	Change in Quality-of-Life Questionnaire Lung Cancer 13 (QLQ-LC13) Symptoms of Dyspnea Subscale		From Baseline to Week 12
Secondary	Change in QLQ-LC13 Symptoms of Cough Subscale		From Baseline to Week 12
Secondary	Change in QLQ-LC13 Symptoms of Chest Pain Subscale		From Baseline to Week 12
Secondary	Change in Physical Function as Measured by QLQ-C30		From Baseline to Week 12
Secondary	Change in Global Health Status as Measured by QLQ-C30		From Baseline to Week 12
Secondary	Progression-free Survival 2 (PFS2)	PFS2 is defined as the time from randomization to progression per investigator after initiation of new anticancer therapy or treatment beyond progression (ie, second progression) or death from any cause, whichever occurs first.	From Baseline up to EOS (approximately 5.5 years)
Secondary	Change in QLQ-LC13 Subscale Scores		From Baseline up to EOS (approximately 5.5 years)
Secondary	Change in QLQ-C30 Subscale Scores		From Baseline up to EOS (approximately 5.5 years)
Secondary	Time to Deterioration in QLC-LC13 Subscale Scores		From Baseline to Week 12
Secondary	Time to Deterioration in QLC-C30 Subscale Scores		From Baseline to Week 12
Secondary	Change in Summary Scores and Visual Analogue Scale (VAS) Scores	Measured by EuroQol-5 Dimension (EQ-5D-5L).	From Baseline up to EOS (approximately 5.5 years)
Secondary	Duration of Response	Duration of response is defined as the time from the first documentation of objective response until the first documentation of disease progression per BICR or death due to any cause, whichever occurs first.	From Baseline up to EOS (approximately 5.5 years)
Secondary	Time to Response	Defined as the time from randomization to first evidence of PR or CR per BICR.	From Baseline up to EOS (approximately 5.5 years)
Secondary	Disease Control	Defined as CR plus PR plus stable disease based on RECIST v1.1 per BICR.	From Baseline up to EOS (approximately 5.5 years)
Secondary	PFS	Based on investigator tumor assessments per RECIST v1.1.	From Baseline up to EOS (approximately 5.5 years)
Secondary	Objective Response	Based on investigator tumor assessments per RECIST v1.1.	From Baseline up to EOS (approximately 5.5 years)
Secondary	Number of Participants With Treatment-Emergent Adverse Events		From Baseline up to EOS (approximately 5.5 years)
Secondary	Number of Participants With Clinically Significant Changes in Vital Signs		From Baseline up to EOS (approximately 5.5 years)
Secondary	Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests		From Baseline up to EOS (approximately 5.5 years)
Secondary	Maximum Plasma Concentration (Cmax) of Sotorasib		Pre-dose Day 1 up to Day 64
Secondary	Minimum Plasma Concentration (Cmin) of Sotorasib		Pre-dose Day 1 up to Day 64
Secondary	Area Under The Curve (AUC) of Sotorasib		Pre-dose Day 1 up to Day 64

External Links

•   AmgenTrials clinical trials website