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
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• 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
• 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.

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

External Links

•   AmgenTrials clinical trials website