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)

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: KRAS p.G12C Mutant Advanced Solid Tumors
• Intervention / Treatment: Drug: sotorasib; Drug: Anti PD-1/L1; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Actual): 713
• Phase: Phase 2; Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Scientia Clinical Research Ltd
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Peter MacCallum Cancer Centre
• Austria
  • Graz, Austria, 8036
    • Medizinische Universitaet Graz
  • Innsbruck, Austria, 6020
    • Medizinische Universitaet Innsbruck
  • Krems, Austria, 3500
    • Universitaetsklinikum Krems
  • Vienna, Austria, 1090
    • Universitaetsklinikum Allgemeines Krankenhaus Wien
  • Vienna, Austria, 1210
    • Krankenhaus Nord - Klinik Floridsdorf
• Belgium
  • Brussels, Belgium, B-1070
    • Institut Jules Bordet
  • Charleroi, Belgium, 6000
    • Grand Hôpital de Charleroi
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Genk, Belgium, 3600
    • Ziekenhuis Oost-Limburg
  • Ghent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis - Campus Virga Jesse
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire de Liège
  • Roeselare, Belgium, 8800
    • AZ Delta Campus Rumbeke
• Brazil
  • Rio de Janeiro, Brazil, 20231-050
    • Instituto Coi
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90050-170
      • Irmandade da Santa Casa de Misericordia de Porto Alegre, Nucleo de Novos Tratamentos em Cancer
  • São Paulo
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Hospital de Base de Sao Jose do Rio Preto
    • São Paulo, São Paulo, Brazil, 01308-050
      • Sociedade Beneficente de Senhoras Hospital Sirio Libanes
    • São Paulo, São Paulo, Brazil, 04501-000
      • Oncologia Rede D´Or
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Regional Cancer Program, London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre Glen Site
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Créteil, France, 94010
    • Centre Hospitalier Intercommunal de Créteil
  • Marseille, France, 13385
    • Hôpital de la Timone
  • Paris, France, 75005
    • Institut Curie
  • Toulouse, France, 31059
    • Institut Claudius Regaud
  • Villejuif, France, 94805
    • Gustave Roussy
• Germany
  • Cologne, Germany, 50937
    • Universitätsklinikum Köln
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • München, Germany, 81377
    • Klinikum der Universität München Campus Grosshadern
• Greece
  • Athens, Greece, 18547
    • Metropolitan Hospital
  • Athens, Greece, 11526
    • Henry Dunant Hospital Center
  • Heraklion - Crete, Greece, 71500
    • University Hospital of Heraklion
  • Thessaloniki, Greece, 54007
    • Theagenion Cancer Hospital
  • Thessaloniki, Greece, 55236
    • Agios Loukas Clinic
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
  • Budapest, Hungary, 1121
    • Orszagos Koranyi Pulmonologiai Intezet
  • Kaposvár, Hungary, 7400
    • Somogy Megyei Kaposi Mor Oktato Korhaz
  • Székesfehérvár, Hungary, 8000
    • Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
  • Tatabánya, Hungary, 2800
    • Szent Borbala Korhaz
  • Törökbálint, Hungary, 2045
    • Tudogyogyintezet Torokbalint
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Aichi Cancer Center
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 811-1395
      • National Hospital Organization Kyushu Cancer Center
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan, 216-8511
      • St Marianna University Hospital
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center
  • Miyagi
    • Sendai, Miyagi, Japan, 980-0873
      • Sendai Kousei Hospital
  • Niigata
    • Niigata, Niigata, Japan, 951-8566
      • Niigata Cancer Center Hospital
  • Okayama-ken
    • Okayama, Okayama-ken, Japan, 700-8558
      • Okayama University Hospital
  • Osaka
    • Hirakata-shi, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital
    • Osaka, Osaka, Japan, 541-8567
      • Osaka International Cancer Institute
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center
  • Tokyo
    • Koto-ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
  • Wakayama
    • Wakayama, Wakayama, Japan, 641-8510
      • Wakayama Medical University Hospital
• Portugal
  • Lisbon, Portugal, 1400-038
    • Fundacao Champalimaud
  • Lisbon, Portugal, 1769-001
    • Centro Hospitalar Universitario de Lisboa Norte EPE - Hospital Pulido Valente
  • Matosinhos Municipality, Portugal, 4464-513
    • Unidade Local de Saude de Matosinhos, EPE - Hospital Pedro Hispano
  • Porto, Portugal, 4100-180
    • Hospital CUF Porto
  • Porto, Portugal, 4099-001
    • Centro Hospitalar Universitario do Porto EPE - Hospital de Santo Antonio
• Romania
  • Bucharest, Romania, 022328
    • Institutul Oncologic, Prof Dr Alexandru Trestioreanu
  • Cluj-Napoca, Romania, 400015
    • Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca
  • Cluj-Napoca, Romania, 400641
    • SC Medisprof SRL
  • Cluj-Napoca, Romania, 407280
    • Centrul de Radioterapie Amethyst Cluj
  • Craiova, Romania, 200347
    • Centrul de Oncologie Sf Nectarie SRL
  • Iași, Romania, 700483
    • Institutul Regional de Oncologie Iasi
  • Ploieşti, Romania, 100337
    • Spitalul Municipal Ploiesti
  • Timișoara, Romania, 300239
    • SC Oncomed SRL
• South Korea
  • Goyang-si Gyeonggi-do, South Korea, 10408
    • National Cancer Center
  • Seongnam-si, Gyeonggi-do, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 06591
    • The Catholic University of Korea Seoul St Marys Hospital
• Spain
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra
  • Madrid, Spain, 28050
    • Hospital Universitario Madrid Sanchinarro
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Marañón
  • Catalonia
    • Badalona, Catalonia, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
  • Valencia
    • Valencia, Valencia, Spain, 46014
      • Hospital General Universitario de Valencia
• Switzerland
  • Basel, Switzerland, 4031
    • Universitaetsspital Basel
  • Geneva, Switzerland, 1211
    • Hôpitaux Universitaires de Genève
  • Zurich, Switzerland, 8091
    • Universitaetsspital Zuerich
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • San Francisco, California, United States, 94115
      • University of California at SF
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Research Center LLC
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Hospital at Yale New Haven
  • Delaware
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants Helen F Graham Cancer Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Health
    • Orlando, Florida, United States, 32804
      • AdventHealth Orlando Infusion Center
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • American Oncology Partners of Maryland, PA
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Missouri
    • St Louis, Missouri, United States, 63110-1093
      • Washington University
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at New York University Langone
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center, Morris Cancer Clinic
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center Cancer Pavillion
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Cancer Center and Research Institute - Spartanburg
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Ingram Cancer Center
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology - Austin Central
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • US Oncology Research Investigational Products Center
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists PC
    • Salem, Virginia, United States, 24153
      • Blue Ridge Cancer Care
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Dose Exploration Part 1 monotherapy; Cohorts with food effect and alternative dosing regimens Enrollment into the dose exploration cohorts may be from any eligible solid tumor type. Dose escalation will begin with 2-4 subjects treated at the lowest planned dose level of 180 mg. If no DLT is observed, dose escalation will continue to the next planned dose cohort	Drug: sotorasib; Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Experimental: Phase 1 Dose Expansion Part 2 monotherapy; Upon completing the dose exploration part of the study, dose expansion may proceed with 3 groups consisting of subjects with KRAS p.G12C mutant advanced solid tumors. Dose expansion in these 3 groups may be done concurrently	Drug: sotorasib; Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Experimental: Phase 1 combination arm with sotorasib and anti PD-1/L1; Additional subjects will be enrolled into the combination arm with sotorasib in combination with an anti (PD-1/L1)	Drug: sotorasib; Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation; Drug: Anti PD-1/L1; Administered as an intravenous (IV) infusion
Experimental: Phase 1 monotherapy treatment naive advanced NSCLC; Separate cohort of part 1 dose expansion subjects to evaluate the safety and clinical activity of sotorasib administered orally once daily in subjects with previously untreated advanced non-small cell lung cancer (NSCLC). Drug-drug interaction will be evaluated in 6 of the subjects enrolled in the treatment naive cohort by adding Midazolam alone on Day -1 and in combination with sotorasib on Day 15 of Cycle 1, where each cycle is 21 days.	Drug: sotorasib; Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation; Drug: Midazolam; Administered as an oral hydrochloride (HCI) syrup
Experimental: Phase 2 monotherapy dose comparison; Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy	Drug: sotorasib; Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Experimental: Phase 1 Does escalation and Expansion monotherapy BID; BID 2L+solid tumors (fed state)	Drug: sotorasib; Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• Lanman BA, Allen JR, Allen JG, Amegadzie AK, Ashton KS, Booker SK, Chen JJ, Chen N, Frohn MJ, Goodman G, Kopecky DJ, Liu L, Lopez P, Low JD, Ma V, Minatti AE, Nguyen TT, Nishimura N, Pickrell AJ, Reed AB, Shin Y, Siegmund AC, Tamayo NA, Tegley CM, Walton MC, Wang HL, Wurz RP, Xue M, Yang KC, Achanta P, Bartberger MD, Canon J, Hollis LS, McCarter JD, Mohr C, Rex K, Saiki AY, San Miguel T, Volak LP, Wang KH, Whittington DA, Zech SG, Lipford JR, Cee VJ. Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors. J Med Chem. 2020 Jan 9;63(1):52-65. doi: 10.1021/acs.jmedchem.9b01180. Epub 2019 Dec 24.
• 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.
• 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.
• Hochmair MJ, Vermaelen K, Mountzios G, Carcereny E, Dooms C, Lee SH, Morocz E, Kato T, Ciuleanu TE, Dy GK, Parente B, O'Byrne KJ, Chu QS, Castro Junior G, Girard N, Snyder W, Tran Q, Kormany W, Houk B, Mehta B, Curioni-Fontecedro A. Sotorasib (960 mg or 240 mg) once daily in patients with previously treated KRAS G12C-mutated advanced NSCLC. Eur J Cancer. 2024 Sep;208:114204. doi: 10.1016/j.ejca.2024.114204. Epub 2024 Jul 5.
• Dilly J, Hoffman MT, Abbassi L, Li Z, Paradiso F, Parent BD, Hennessey CJ, Jordan AC, Morgado M, Dasgupta S, Uribe GA, Yang A, Kapner KS, Hambitzer FP, Qiang L, Feng H, Geisberg J, Wang J, Evans KE, Lyu H, Schalck A, Feng N, Lopez AM, Bristow CA, Kim MP, Rajapakshe KI, Bahrambeigi V, Roth JA, Garg K, Guerrero PA, Stanger BZ, Cristea S, Lowe SW, Baslan T, Van Allen EM, Mancias JD, Chan E, Anderson A, Katlinskaya YV, Shalek AK, Hong DS, Pant S, Hallin J, Anderes K, Olson P, Heffernan TP, Chugh S, Christensen JG, Maitra A, Wolpin BM, Raghavan S, Nowak JA, Winter PS, Dougan SK, Aguirre AJ. Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer. Cancer Discov. 2024 Nov 1;14(11):2135-2161. doi: 10.1158/2159-8290.CD-24-0177.
• Nagase M, Houk B, Vuu I, Cardona P, Dutta S, Lin CW. Population Pharmacokinetics of Sotorasib in Healthy Subjects and Advanced Solid Tumor Patients Harboring a KRASG12C Mutation from Phase 1 and Phase 2 Studies. AAPS J. 2025 Jan 13;27(1):26. doi: 10.1208/s12248-024-01013-6.
• Strickler JH, Satake H, George TJ, Yaeger R, Hollebecque A, Garrido-Laguna I, Schuler M, Burns TF, Coveler AL, Falchook GS, Vincent M, Sunakawa Y, Dahan L, Bajor D, Rha SY, Lemech C, Juric D, Rehn M, Ngarmchamnanrith G, Jafarinasabian P, Tran Q, Hong DS. Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer. N Engl J Med. 2023 Jan 5;388(1):33-43. doi: 10.1056/NEJMoa2208470. Epub 2022 Dec 21.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2018
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): May 30, 2026

Study Registration Dates

• First Submitted: June 26, 2018
• First Submitted That Met QC Criteria: July 17, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Benzodiazepines; Midazolam; sotorasib
• Other Study ID Numbers: 20170543

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No