NCT04185883

Brief Summary

To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
610

participants targeted

Target at P75+ for phase_1

Timeline
19mo left

Started Dec 2019

Longer than P75 for phase_1

Geographic Reach
12 countries

85 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress80%
Dec 2019Dec 2027

First Submitted

Initial submission to the registry

December 3, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 4, 2019

Completed
13 days until next milestone

Study Start

First participant enrolled

December 17, 2019

Completed
7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 17, 2026

Expected
12 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 5, 2027

Last Updated

October 22, 2025

Status Verified

October 1, 2025

Enrollment Period

7 years

First QC Date

December 3, 2019

Last Update Submit

October 21, 2025

Conditions

Outcome Measures

Primary Outcomes (6)

  • Number of Participants with Dose Limiting Toxicities (DLTs)

    12 Months

  • Number of Participants with Treatment-emergent Adverse Events (TEAEs)

    12 Months

  • Number of Participants with Treatment-related Adverse Events

    12 Months

  • Number of Participants with Clinically Significant Changes in Vital Signs

    12 Months

  • Number of Participants with Clinically Significant Changes in ECG Measurements

    12 Months

  • Number of Participants with Clinically Significant Changes in Laboratory Test Values

    12 Months

Secondary Outcomes (25)

  • Maximum Plasma Concentration (Cmax)

    12 Months

  • Time to Maximum Plasma Concentration (Tmax)

    12 Months

  • Area Under the Plasma Concentration-time Curve (AUC)

    12 Months

  • Objective Response Rate

    12 Months

  • Disease Control Rate

    12 Months

  • +20 more secondary outcomes

Study Arms (14)

Sotorasib + trametinib + panitumumab

EXPERIMENTAL

Experimental: Sotorasib + trametinib + panitumumab Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.

Drug: SotorasibDrug: TrametinibDrug: Panitumumab

Sotorasib + RMC-4630

EXPERIMENTAL

Experimental: Sotorasib + RMC-4630 Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants, with KRAS p.G12C mutant advanced solid tumors.

Drug: SotorasibDrug: RMC-4630

Sotorasib + afatinib

EXPERIMENTAL

Experimental: Sotorasib + afatinib Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.

Drug: SotorasibDrug: Afatinib

Sotorasib + panitumumab +/- chemotherapy

EXPERIMENTAL

Experimental: Sotorasib + panitumumab +/- chemotherapy Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.

Drug: SotorasibDrug: PanitumumabDrug: IV Chemotherapy (Regimen 1)

Sotorasib + atezolizumab

EXPERIMENTAL

Experimental: Sotorasib + atezolizumab Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.

Drug: SotorasibDrug: Atezolizumab

Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab

EXPERIMENTAL

Experimental: Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.

Drug: SotorasibDrug: PembrolizumabDrug: Carboplatin, pemetrexed, docetaxel, paclitaxel

Sotorasib Monotherapy

EXPERIMENTAL

Experimental: Sotorasib only Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer with brain metastases. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer with brain metastases.

Drug: Sotorasib

Sotorasib + palbociclib

EXPERIMENTAL

Experimental: Sotorasib + palbociclib Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.

Drug: SotorasibDrug: Palbociclib

Sotorasib + pembrolizumab

EXPERIMENTAL

Experimental: Sotorasib + pembrolizumab Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant non small cell lung cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS P.G12C mutant non small cell lung cancer.

Drug: SotorasibDrug: Pembrolizumab

Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy

EXPERIMENTAL

Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ chemotherapy Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced colorectal cancer.

Drug: SotorasibDrug: MVASI® (bevacizumab-awwb)Drug: IV Chemotherapy (Regimen 1)Drug: IV Chemotherapy (Regimen 2)

Sotorasib + TNO155

EXPERIMENTAL

Experimental: Sotorasib + TNO155 Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.

Drug: SotorasibDrug: TNO155

Sotorasib + BI 1701963

EXPERIMENTAL

Experimental: Sotorasib + BI 1701963 Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. * Upon completion of dose exploration part of the study the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced non-small cell lung cancer and advanced colorectal cancer.

Drug: SotorasibDrug: BI 1701963

Sotorasib + AMG 404

EXPERIMENTAL

Experimental: Sotorasib + AMG 404 Dose Exploration and Dose Expansion • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors

Drug: SotorasibDrug: AMG 404

Sotorasib + everolimus

EXPERIMENTAL

Experimental: Sotorasib + everolimus Dose Exploration and Dose Expansion • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor. • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.

Drug: SotorasibDrug: Everolimus

Interventions

Sotorasib administered orally as a tablet.

Sotorasib + AMG 404Sotorasib + BI 1701963Sotorasib + MVASI® (bevacizumab-awwb)+ ChemotherapySotorasib + RMC-4630Sotorasib + TNO155Sotorasib + afatinibSotorasib + atezolizumabSotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumabSotorasib + everolimusSotorasib + palbociclibSotorasib + panitumumab +/- chemotherapySotorasib + pembrolizumabSotorasib + trametinib + panitumumabSotorasib Monotherapy

Trametinib administered orally as a tablet.

Sotorasib + trametinib + panitumumab

RMC-4630 administered orally as a capsule.

Sotorasib + RMC-4630

afatinib administered orally as a tablet.

Sotorasib + afatinib

pembrolizumab administered as an intravenous (IV) infusion.

Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumabSotorasib + pembrolizumab

Panitumumab administered as an IV infusion.

Sotorasib + panitumumab +/- chemotherapySotorasib + trametinib + panitumumab

Carboplatin, pemetrexed, docetaxel administered as an IV infusion.

Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab

Atezolizumab administered as an IV injection.

Sotorasib + atezolizumab

Palbociclib administered orally as a tablet.

Sotorasib + palbociclib

MVASI® (bevacizumab-awwb) administered as an IV infusion.

Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy
TNO155DRUG

TNO155 administered orally as a capsule.

Sotorasib + TNO155

Chemotherapy combination of leucovorin administered as an IV injection, 5-fluorouracil (5-FU) administered as IV bolus injection or IV continuous infusion (depending on dose), and irinotecan administered as IV injection.

Sotorasib + MVASI® (bevacizumab-awwb)+ ChemotherapySotorasib + panitumumab +/- chemotherapy

IV chemotherapy combination of leucovorin administered as an IV injection, 5-FU administered as IV bolus injection or IV continuous infusion (depending on dose), and oxaliplatin administered as IV injection.

Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy

BI 1701963 administered orally

Sotorasib + BI 1701963

AMG 404 administered as an IV infusion.

Sotorasib + AMG 404

Everolimus administered orally.

Sotorasib + everolimus

Eligibility Criteria

Age18 Years - 100 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 performed according to in-country requirements. In the United States, this test must be performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.

You may not qualify if:

  • Primary brain tumor.
  • Spinal cord compression, or untreated, or symptomatic, or active brain metastases, or leptomeningeal disease from non-brain tumors.
  • Myocardial infarction within 6 months of study day 1.
  • Gastrointestinal (GI) tract disease causing the inability to take oral medication.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (90)

Arizona Oncology Associates Professional Corporation

Tucson, Arizona, 85711, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Loma Linda University Cancer Center

Loma Linda, California, 92354, United States

Location

University of Southern California, Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California San Francisco Mission Bay Campus

San Francisco, California, 94115, United States

Location

University of California Los Angeles

Santa Monica, California, 90404, United States

Location

Rocky Mountain Cancer Centers Denver Midtown

Denver, Colorado, 80218, United States

Location

Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

Norwalk Hospital

Norwalk, Connecticut, 06856, United States

Location

Memorial Cancer Institute

Pembroke Pines, Florida, 33028, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-5912, United States

Location

Henry Ford Cancer Detroit (Brigitte Harris Cancer Pavilion)

Detroit, Michigan, 48202, United States

Location

Washington University

St Louis, Missouri, 63110-1093, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 32224, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Gibbs Cancer Center and Research Institute - Spartanburg

Spartanburg, South Carolina, 29303, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57108, United States

Location

United States Oncology Regulatory Affairs Corporate Office

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Oncology Central-South

Austin, Texas, 78705, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Oncology Consultants

Houston, Texas, 77030, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

US Oncology Research Investigational Products Center

The Woodlands, Texas, 77380, United States

Location

Texas Oncology Northeast Texas

Tyler, Texas, 75702, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22903, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

Location

Northwest Cancer Specialists - Vancouver

Vancouver, Washington, 98684, United States

Location

Nepean Cancer Centre

Kingswood, New South Wales, 2747, Australia

Location

GenesisCare -North Shore Oncology

St Leonards, New South Wales, 2065, Australia

Location

Icon Cancer Care South Brisbane

South Brisbane, Queensland, 4101, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

St John of God Healthcare

Subiaco, Western Australia, 6008, Australia

Location

Medizinische Universitaet Graz

Graz, 8036, Austria

Location

Landeskrankenhaus Salzburg

Salzburg, 5020, Austria

Location

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

CHU de Quebec Hopital de l Enfant Jesus

Québec, Quebec, G1J 1Z4, Canada

Location

Charite Universitaetsmedizin Berlin, Campus Virchow

Berlin, 13353, Germany

Location

Universitatsklinikum Koln

Cologne, 50937, Germany

Location

Universitaetsklinikum Dresden

Dresden, 01307, Germany

Location

Universitaetsklinikum Essen

Essen, 45147, Germany

Location

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

Location

Centro Ricerche Cliniche Di Verona Societa responsabilita limitata

Verona, 37126, Italy

Location

Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo, 135-8550, Japan

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

The Catholic University of Korea Seoul St Marys Hospital

Seoul, 06591, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Institut Catala d Oncologia Hospitalet Hospital Duran i Reynals

L'Hospitalet de Llobregat, Catalonia, 08908, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

Taoyuan District, 33305, Taiwan

Location

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

Location

Related Publications (1)

  • Kuboki Y, Fakih M, Strickler J, Yaeger R, Masuishi T, Kim EJ, Bestvina CM, Kopetz S, Falchook GS, Langer C, Krauss J, Puri S, Cardona P, Chan E, Varrieur T, Mukundan L, Anderson A, Tran Q, Hong DS. Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial. Nat Med. 2024 Jan;30(1):265-270. doi: 10.1038/s41591-023-02717-6. Epub 2024 Jan 4.

    PMID: 38177853BACKGROUND

Related Links

MeSH Terms

Interventions

sotorasibtrametinibAfatinibpembrolizumabPanitumumabCarboplatinPemetrexedDocetaxelPaclitaxelatezolizumabpalbociclibBevacizumabDrug TherapyEverolimus

Intervention Hierarchy (Ancestors)

AmidesOrganic ChemicalsQuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsCoordination ComplexesGuanineHypoxanthinesPurinonesPurinesGlutamatesAmino Acids, AcidicAmino AcidsAmino Acids, DicarboxylicTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsDiterpenesTerpenesTherapeuticsSirolimusMacrolidesLactones

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

December 3, 2019

First Posted

December 4, 2019

Study Start

December 17, 2019

Primary Completion (Estimated)

December 17, 2026

Study Completion (Estimated)

December 5, 2027

Last Updated

October 22, 2025

Record last verified: 2025-10

Data Sharing

IPD Sharing
Will share

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR
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 (or other new use) 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.
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, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. 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.
More information

Locations