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NCT03600883 Clinical Trial

A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of Sotorasib (AMG 510) in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)

KRAS p.G12C Mutant Advanced Solid Tumors Clinical Trial

Official title:
A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Sotorasib (AMG 510) Monotherapy in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation and Sotorasib (AMG 510) Combination Therapy in Subjects With Advanced NSCLC With KRAS p.G12C Mutation (CodeBreaK 100)

Clinical Trial Details — Status: Active, not recruiting

Administrative data
NCT number NCT03600883
Other study ID # 20170543
Secondary ID
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date August 27, 2018
Est. completion date November 8, 2027

Study information
Verified date May 2024
Source Amgen
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Evaluate the safety and tolerability of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors. Estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) in adult subjects with KRAS p.G12C mutant advanced solid tumors.

Recruitment information / eligibility
Status Active, not recruiting
Enrollment 713
Est. completion date November 8, 2027
Est. primary completion date November 8, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years to 100 Years
Eligibility Inclusion Criteria: - Men or women greater than or equal to 18 years old. - Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing. Exclusion Criteria - Active brain metastases from non-brain tumors. - Myocardial infarction within 6 months of study day 1. - Gastrointestinal (GI) tract disease causing the inability to take oral medication.

Study Design

Related Conditions & MeSH terms

  • KRAS p.G12C Mutant Advanced Solid Tumors
  • Neoplasms

Intervention

Drug:
• sotorasib
Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
• Anti PD-1/L1
Administered as an intravenous (IV) infusion
• Midazolam
Administered as an oral hydrochloride (HCI) syrup

Locations
Country Name City State
Australia Peter MacCallum Cancer Centre Parkville Victoria
Australia Scientia Clinical Research Ltd Randwick New South Wales
Australia The Queen Elizabeth Hospital Woodville South South Australia
Australia Princess Alexandra Hospital Woolloongabba Queensland
Austria Medizinische Universitaet Graz Graz
Austria Medizinische Universitaet Innsbruck Innsbruck
Austria Universitaetsklinikum Krems Krems
Austria Krankenhaus Nord - Klinik Floridsdorf Wien
Austria Universitaetsklinikum Allgemeines Krankenhaus Wien Wien
Belgium Institut Jules Bordet Brussels
Belgium Grand Hopital de Charleroi Charleroi
Belgium Universitair Ziekenhuis Antwerpen Edegem
Belgium Ziekenhuis Oost-Limburg Genk
Belgium Universitair Ziekenhuis Gent Gent
Belgium Jessa Ziekenhuis - Campus Virga Jesse Hasselt
Belgium Universitair Ziekenhuis Leuven - Campus Gasthuisberg Leuven
Belgium Centre Hospitalier Universitaire de Liege Liege
Belgium AZ Delta Campus Rumbeke Roeselare
Brazil Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul Porto Alegre Rio Grande Do Sul
Brazil Irmandade da Santa Casa de Misericordia de Porto Alegre, Nucleo de Novos Tratamentos em Cancer Porto Alegre Rio Grande Do Sul
Brazil Instituto Coi Rio de Janeiro
Brazil Hospital de Base de Sao Jose do Rio Preto São José do Rio Preto São Paulo
Brazil Oncologia Rede D´Or Sao Paulo São Paulo
Brazil Sociedade Beneficente de Senhoras Hospital Sirio Libanes Sao Paulo São Paulo
Canada Tom Baker Cancer Centre Calgary Alberta
Canada Cross Cancer Institute Edmonton Alberta
Canada London Regional Cancer Program, London Health Sciences Centre London Ontario
Canada McGill University Health Centre Glen Site Montreal Quebec
Canada The Ottawa Hospital Cancer Centre Ottawa Ontario
Canada Princess Margaret Cancer Centre Toronto Ontario
France Institut Bergonie Bordeaux
France Centre Hospitalier Intercommunal de Créteil Créteil
France Hopital de la Timone Marseille cedex 5
France Institut Curie Paris
France Institut Claudius Regaud Toulouse cedex 9
France Gustave Roussy Villejuif
Germany Universitätsklinikum Essen Essen
Germany Universitatsklinikum Koln Köln
Germany Klinikum der Universität München Campus Grosshadern München
Greece Henry Dunant Hospital Center Athens
Greece Metropolitan Hospital Athens
Greece University Hospital of Heraklion Heraklion - Crete
Greece Agios Loukas Clinic Thessaloniki
Greece Theagenion Cancer Hospital Thessaloniki
Hungary Orszagos Koranyi Pulmonologiai Intezet Budapest
Hungary Semmelweis Egyetem Budapest
Hungary Somogy Megyei Kaposi Mor Oktato Korhaz Kaposvar
Hungary Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz Szekesfehervar
Hungary Szent Borbala Korhaz Tatabanya
Hungary Tudogyogyintezet Torokbalint Torokbalint
Japan National Hospital Organization Kyushu Cancer Center Fukuoka-shi Fukuoka
Japan Kansai Medical University Hospital Hirakata-shi Osaka
Japan National Cancer Center Hospital East Kashiwa-shi Chiba
Japan St Marianna University Hospital Kawasaki-shi Kanagawa
Japan The Cancer Institute Hospital of Japanese Foundation for Cancer Research Koto-ku Tokyo
Japan National Hospital Organization Shikoku Cancer Center Matsuyama-shi Ehime
Japan Aichi Cancer Center Nagoya-shi Aichi
Japan Niigata Cancer Center Hospital Niigata-shi Niigata
Japan Okayama University Hospital Okayama-shi Okayama
Japan Osaka International Cancer Institute Osaka-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 Wakayama Medical University Hospital Wakayama-shi Wakayama
Japan Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center Yokohama-shi Kanagawa
Korea, Republic of National Cancer Center Goyang-si Gyeonggi-do
Korea, Republic of Seoul National University Bundang Hospital Seongnam-si, Gyeonggi-do
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of Severance Hospital Yonsei University Health System Seoul
Korea, Republic of The Catholic University of Korea Seoul St Marys Hospital Seoul
Portugal Centro Hospitalar Universitario de Lisboa Norte EPE - Hospital Pulido Valente Lisboa
Portugal Fundacao Champalimaud Lisboa
Portugal Unidade Local de Saude de Matosinhos, EPE - Hospital Pedro Hispano Matosinhos
Portugal Centro Hospitalar Universitario do Porto EPE - Hospital de Santo Antonio Porto
Portugal Hospital Cuf porto Porto
Romania Institutul Oncologic, Prof Dr Alexandru Trestioreanu Bucuresti
Romania Centrul de Radioterapie Amethyst Cluj Cluj Napoca
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 Universitari Germans Trias i Pujol Badalona Cataluña
Spain Clinica Universidad de Navarra Madrid
Spain Fundacion Jimenez Diaz Madrid
Spain Hospital General Universitario Gregorio Marañon Madrid
Spain Hospital Universitario Madrid Sanchinarro Madrid
Spain Hospital General Universitario de Valencia Valencia Comunidad Valenciana
Switzerland Universitaetsspital Basel Basel
Switzerland Hopitaux Universitaires de Geneve Geneve
Switzerland Universitaetsspital Zuerich Zurich
United States University of Michigan Ann Arbor Michigan
United States Winship Cancer Institute Atlanta Georgia
United States Texas Oncology - Austin Central Austin Texas
United States American Oncology Partners of Maryland, PA Bethesda Maryland
United States Dana Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States Roswell Park Cancer Institute Buffalo New York
United States Cleveland Clinic Cleveland Ohio
United States University Hospitals Cleveland Medical Center Cleveland Ohio
United States Texas Oncology - Baylor Dallas Texas
United States University of Texas Southwestern Medical Center Dallas Texas
United States Rocky Mountain Cancer Centers Denver Colorado
United States Sarah Cannon Research Institute at HealthONE Denver Colorado
United States Henry Ford Health System Detroit Michigan
United States City of Hope National Medical Center Duarte California
United States Duke University Medical Center, Morris Cancer Clinic Durham North Carolina
United States US Oncology Research Investigational Products Center Fairfax Virginia
United States Virginia Cancer Specialists PC Fairfax Virginia
United States University of Florida Health Gainesville Florida
United States University of Texas MD Anderson Cancer Center Houston Texas
United States Indiana University Indianapolis Indiana
United States University of California Los Angeles Los Angeles California
United States Vanderbilt University Ingram Cancer Center Nashville Tennessee
United States Smilow Cancer Hospital at Yale New Haven New Haven Connecticut
United States Laura and Isaac Perlmutter Cancer Center at New York University Langone New York New York
United States Memorial Sloan Kettering Cancer Center New York New York
United States Medical Oncology Hematology Consultants Helen F Graham Cancer Center Newark Delaware
United States AdventHealth Orlando Infusion Center Orlando Florida
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States University of Pennsylvania Philadelphia Pennsylvania
United States University of Pittsburgh Medical Center Cancer Pavillion Pittsburgh Pennsylvania
United States Washington University Saint Louis Missouri
United States Blue Ridge Cancer Care Salem Virginia
United States Huntsman Cancer Institute Salt Lake City Utah
United States University of California at SF San Francisco California
United States Sarcoma Oncology Research Center LLC Santa Monica California
United States Seattle Cancer Care Alliance Seattle Washington
United States Gibbs Cancer Center and Research Institute - Spartanburg Spartanburg South Carolina
United States Moffitt Cancer Center Tampa Florida

Sponsors (1)
Lead Sponsor Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  France,  Germany,  Greece,  Hungary,  Japan,  Korea, Republic of,  Portugal,  Romania,  Spain,  Switzerland, 

References & Publications (7)

Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, Lanman BA, Werner J, Rapaport AS, San Miguel T, Ortiz R, Osgood T, Sun JR, Zhu X, McCarter JD, Volak LP, Houk BE, Fakih MG, O'Neil BH, Price TJ, Falchook GS, Desai J, Kuo J, Govindan R, Hong DS, Ouyang W, Henary H, Arvedson T, Cee VJ, Lipford JR. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217-223. doi: 10.1038/s41586-019-1694-1. Epub 2019 Oct 30. — View Citation

Dy GK, Govindan R, Velcheti V, Falchook GS, Italiano A, Wolf J, Sacher AG, Takahashi T, Ramalingam SS, Dooms C, Kim DW, Addeo A, Desai J, Schuler M, Tomasini P, Hong DS, Lito P, Tran Q, Jones S, Anderson A, Hindoyan A, Snyder W, Skoulidis F, Li BT. Long-term benefit of sotorasib in patients with KRAS G12C-mutated non-small-cell lung cancer: plain language summary. Future Oncol. 2024 Jan;20(3):113-120. doi: 10.2217/fon-2023-0560. Epub 2023 Nov 27. — View Citation

Dy GK, Govindan R, Velcheti V, Falchook GS, Italiano A, Wolf J, Sacher AG, Takahashi T, Ramalingam SS, Dooms C, Kim DW, Addeo A, Desai J, Schuler M, Tomasini P, Hong DS, Lito P, Tran Q, Jones S, Anderson A, Hindoyan A, Snyder W, Skoulidis F, Li BT. Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated KRAS G12C-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis of CodeBreaK 100. J Clin Oncol. 2023 Jun 20;41(18):3311-3317. doi: 10.1200/JCO.22.02524. Epub 2023 Apr 25. — View Citation

Fakih MG, Kopetz S, Kuboki Y, Kim TW, Munster PN, Krauss JC, Falchook GS, Han SW, Heinemann V, Muro K, Strickler JH, Hong DS, Denlinger CS, Girotto G, Lee MA, Henary H, Tran Q, Park JK, Ngarmchamnanrith G, Prenen H, Price TJ. Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol. 2022 Jan;23(1):115-124. doi: 10.1016/S1470-2045(21)00605-7. Epub 2021 Dec 15. — View Citation

Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, Falchook GS, Price TJ, Sacher A, Denlinger CS, Bang YJ, Dy GK, Krauss JC, Kuboki Y, Kuo JC, Coveler AL, Park K, Kim TW, Barlesi F, Munster PN, Ramalingam SS, Burns TF, Meric-Bernstam F, Henary H, Ngang J, Ngarmchamnanrith G, Kim J, Houk BE, Canon J, Lipford JR, Friberg G, Lito P, Govindan R, Li BT. KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020 Sep 24;383(13):1207-1217. doi: 10.1056/NEJMoa1917239. Epub 2020 Sep 20. — View Citation

Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, Kato T, Curioni-Fontecedro A, Sacher A, Spira A, Ramalingam SS, Takahashi T, Besse B, Anderson A, Ang A, Tran Q, Mather O, Henary H, Ngarmchamnanrith G, Friberg G, Velcheti V, Govindan R. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med. 2021 Jun 24;384(25):2371-2381. doi: 10.1056/NEJMoa2103695. Epub 2021 Jun 4. — View Citation

Zhao Y, Murciano-Goroff YR, Xue JY, Ang A, Lucas J, Mai TT, Da Cruz Paula AF, Saiki AY, Mohn D, Achanta P, Sisk AE, Arora KS, Roy RS, Kim D, Li C, Lim LP, Li M, Bahr A, Loomis BR, de Stanchina E, Reis-Filho JS, Weigelt B, Berger M, Riely G, Arbour KC, Lipford JR, Li BT, Lito P. Diverse alterations associated with resistance to KRAS(G12C) inhibition. Nature. 2021 Nov;599(7886):679-683. doi: 10.1038/s41586-021-04065-2. Epub 2021 Nov 10. — View Citation

Outcome
Type Measure Description Time frame Safety issue
Primary Primary: Number of subjects with treatment-emergent adverse events Treatment-emergent adverse events will be a primary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 1 monotherapy treatment naïve advanced NSCLC
Phase 2 monotherapy dose comparison		 24 Months
Primary Primary: Number of subjects with treatment-related adverse events Treatment-related adverse events will be a primary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 1 monotherapy treatment naïve advanced NSCLC		 24 Months
Primary Primary: Number of subjects with grade =3 treatment-emergent adverse events Grade =3 treatment-emergent adverse events will be a primary outcome measure in the following group:
- Phase 2 monotherapy dose comparison		 24 Months
Primary Primary: Number of subjects with serious adverse events Serious adverse events will be a primary outcome measure in the following group:
- Phase 2 monotherapy dose comparison		 24 Months
Primary Primary: Number of subjects with adverse events of interest Adverse events of interest will be a primary outcome measure in the following group:
- Phase 2 monotherapy dose comparison		 24 Months
Primary Primary: Number of subjects with clinically significant changes in vital signs Vital signs will be a primary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 1 monotherapy treatment naïve advanced NSCLC		 Baseline to 24 Months
Primary Primary: Number of subjects with clinically significant changes in physical examination results Physical examinations will be a primary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1		 Baseline to 24 Months
Primary Primary: Number of subjects with clinically significant changes on electrocardiograms (ECGs) ECGs will be a primary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 1 monotherapy treatment naïve advanced NSCLC		 Baseline to 24 Months
Primary Primary: Number of subjects with clinically significant changes in clinical laboratory values Abnormal clinical laboratory values will be a primary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 1 monotherapy treatment naïve advanced NSCLC		 Baseline to 24 Months
Primary Primary: Number of subjects with dose-limiting toxicities (DLTs) DLTs will be a primary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 1 monotherapy treatment naïve advanced NSCLC		 21 Days
Primary Primary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria ORR will be a primary outcome measure in the following group:
Phase 1 monotherapy treatment naïve advanced NSCLC
Phase 2 monotherapy
Phase 2 monotherapy dose comparison		 24 Months
Primary Primary: Duration of response (DOR) as assessed by RECIST 1.1 criteria DOR will be a primary outcome measure in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLC		 24 Months
Primary Primary: Disease control as assessed by RECIST 1.1 criteria Disease control will be a primary outcome measure in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLC		 24 Months
Primary Primary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria Duration of SD will be a primary outcome measure in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLC		 24 Months
Primary Primary: Time to response (TTR) as assessed by RECIST 1.1 criteria TTR will be a primary outcome measure in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLC		 24 Months
Secondary Secondary: Plasma concentration (Cmax) of sotorasib Cmax will be a secondary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 1 monotherapy treatment naïve advanced NSCLC
Phase 2 monotherapy dose comparison		 15 Weeks
Secondary Secondary: Plasma concentration (Cmax) of midazolam Cmax of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLC		 16 Days
Secondary Secondary: Time to achieve Cmax (Tmax) of sotorasib Tmax will be a secondary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 1 monotherapy treatment naïve advanced NSCLC		 15 Weeks
Secondary Secondary: Area under the plasma concentration-time curve (AUC) of sotorasib AUC will be a secondary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 1 monotherapy treatment naïve advanced NSCLC
Phase 2 monotherapy dose comparison		 15 Weeks
Secondary Secondary: Area under the plasma concentration-time curve (AUC) of midazolam AUC of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLC		 16 Days
Secondary Secondary: Clearance of midazolam from the plasma Clearance of midazolam from the plasma will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLC		 16 Days
Secondary Secondary: Terminal half-life (t1/2) of midazolam t1/2 of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLC		 16 Days
Secondary Secondary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria ORR will be a secondary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1		 24 Months
Secondary Secondary: Duration of response (DOR) as assessed by RECIST 1.1 criteria DOR will be a secondary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 2 monotherapy dose comparison		 24 Months
Secondary Secondary: Disease control as assessed by RECIST 1.1 criteria DOR will be a secondary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 2 monotherapy dose comparison		 24 Months
Secondary Secondary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria PFS will be a secondary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 2 monotherapy dose comparison
Phase 1 monotherapy treatment naïve advanced NSCLC		 24 Months
Secondary Secondary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria Duration of SD will be a secondary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1		 24 Months
Secondary Secondary: Depth of response (best percentage change from baseline in lesion sum diameters) as assessed by RECIST 1.1 criteria Depth of response will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparison		 Baseline to 24 Months
Secondary Secondary: Time to response (TTR) as assessed by RECIST 1.1 criteria DOR will be a secondary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 2 monotherapy dose comparison		 24 Months
Secondary Secondary: Overall survival (OS) OS will be a secondary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy
Phase 2 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 2 monotherapy dose comparison
Phase 1 monotherapy treatment naïve advanced NSCLC		 24 Months
Secondary Secondary: sotorasib exposure and QTc interval relationship sotorasib exposure and QTc interval relationship will be a secondary outcome measure for the following groups:
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 Dose Expansion Part 2 monotherapy		 24 Months
Secondary Secondary: Progression-free survival (PFS) at 6 months PFS at 6 months will be a secondary outcome measure for the following group:
- Phase 2 monotherapy		 6 Months
Secondary Secondary: Progression-free survival (PFS) at 12 months PFS at 12 months will be a secondary outcome measure for the following group:
- Phase 2 monotherapy		 12 Months
Secondary Secondary: Overall survival (OS) at 12 months OS at 12 months will be a secondary outcome measure for the following group:
- Phase 2 monotherapy		 12 Months
Secondary Secondary: Number of subjects with treatment-emergent adverse events Treatment-emergent adverse events will be a secondary outcome measure for the following group:
- Phase 2 monotherapy		 24 Months
Secondary Secondary: Number of subjects with grade =3 treatment-emergent adverse events Grade =3 treatment-emergent adverse events will be a secondary outcome measure for the following group:
- Phase 2 monotherapy		 24 Months
Secondary Secondary: Impact of treatment on disease-related symptoms and health related quality of life (HRQOL) as assessed by EORTC QLQ-C30 Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparison		 24 Months
Secondary Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by disease-specific modules Quality-of-Life Questionnaire Lung Cancer Module (QLQ LC13) Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparison		 24 Months
Secondary Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by non-small cell lung cancer symptom assessment questionnaire (NSCLC SAQ) for NSCLC Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparison		 24 Months
Secondary Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Severity (PGIS) Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparison		 24 Months
Secondary Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Change (PGIC) in cough, dyspnea and chest pain for NSCLC Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparison		 24 Months
Secondary Secondary: Treatment-related symptoms and impact on the subject as assessed by EORTC QLQ-C30 Treament related symptoms and impact on the subject will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparison		 24 Months
Secondary Secondary: Treatment-related symptoms and impact on the subject as assessed by selected questions from the Patient-reported Outcome of the Common Terminology Criteria for Adverse Events (PRO-CTCAE library) Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparison		 24 Months
Secondary Secondary: Treatment-related symptoms and impact on the subject as assessed by a single item about symptom bother, item GP5 of the Functional Assessment of Cancer Therapy - General (FACT-G) Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparison		 24 Months
Secondary Secondary: Change from baseline in physical function as assessed by EORTC QLQ-C30 Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparison		 Baseline to 24 Months

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