Advanced Solid TumorsPhase 1NCT04185883
Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
A Phase 1 study testing Sotorasib, Trametinib and RMC-4630 in people with Advanced Solid Tumors and Kirsten Rat Sarcoma (KRAS) pG12C Mutation, run by Amgen at 90 sites in 13 countries.
Trial summary
To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Advanced Solid Tumors, Kirsten Rat Sarcoma (KRAS) pG12C Mutation
- What is being tested?
- Sotorasib, Trametinib and RMC-4630
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 610 participants
- Where
- 90 sitesin 13 countries
- Study dates
- 17 Dec 2019to 5 Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
90 sites in 13 countries.
90 sites in 13 countries
United States55 sites
University of Michigan
Ann Arbor, Michigan, 48109-5912
Emory University
Atlanta, Georgia, 30322
Texas Oncology Central-South
Austin, Texas, 78705
Johns Hopkins University
Baltimore, Maryland, 21224
Roswell Park Cancer Institute
Buffalo, New York, 32224
Levine Cancer Institute
Charlotte, North Carolina, 28204
University of Virginia Cancer Center
Charlottesville, Virginia, 22903
Northwestern University
Chicago, Illinois, 60611
University of Chicago
Chicago, Illinois, 60637
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Mary Crowley Cancer Research
Dallas, Texas, 75230
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Rocky Mountain Cancer Centers Denver Midtown
Denver, Colorado, 80218
Sarah Cannon Research Institute
Denver, Colorado, 80218
Henry Ford Cancer Detroit (Brigitte Harris Cancer Pavilion)
Detroit, Michigan, 48202
City of Hope National Medical Center
Duarte, California, 91010
Duke University
Durham, North Carolina, 27710
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
Oncology Consultants
Houston, Texas, 77030
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of California San Diego Moores Cancer Center
La Jolla, California, 92093
Loma Linda University Cancer Center
Loma Linda, California, 92354
University of Southern California, Norris Comprehensive Cancer Center
Los Angeles, California, 90033
United States Oncology Regulatory Affairs Corporate Office
Nashville, Tennessee, 37203
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Yale New Haven Hospital
New Haven, Connecticut, 06520
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Columbia University Irving Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Norwalk Hospital
Norwalk, Connecticut, 06856
Memorial Cancer Institute
Pembroke Pines, Florida, 33028
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
University of Pennsylvania
Philadelphia, Pennsylvania, 19111
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
Providence Portland Medical Center
Portland, Oregon, 97213
Oregon Health and Science University
Portland, Oregon, 97239
University of California Davis Medical Center
Sacramento, California, 95817
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
University of California San Francisco Mission Bay Campus
San Francisco, California, 94115
University of California Los Angeles
Santa Monica, California, 90404
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Avera Cancer Institute
Sioux Falls, South Dakota, 57108
Gibbs Cancer Center and Research Institute - Spartanburg
Spartanburg, South Carolina, 29303
Washington University
St Louis, Missouri, 63110-1093
Northwest Medical Specialties, PLLC
Tacoma, Washington, 98405
Moffitt Cancer Center
Tampa, Florida, 33612
Montefiore Medical Center
The Bronx, New York, 10461
US Oncology Research Investigational Products Center
The Woodlands, Texas, 77380
Arizona Oncology Associates Professional Corporation
Tucson, Arizona, 85711
Texas Oncology Northeast Texas
Tyler, Texas, 75702
Northwest Cancer Specialists - Vancouver
Vancouver, Washington, 98684
Spain6 sites
Hospital Universitari Vall d Hebron
Barcelona, Catalonia, 08035
Hospital Clinic i Provincial de Barcelona
Barcelona, Catalonia, 08036
Institut Catala d Oncologia Hospitalet Hospital Duran i Reynals
L'Hospitalet de Llobregat, Catalonia, 08908
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222
Australia5 sites
Nepean Cancer Centre
Kingswood, New South Wales, 2747
Icon Cancer Care South Brisbane
South Brisbane, Queensland, 4101
GenesisCare -North Shore Oncology
St Leonards, New South Wales, 2065
St John of God Healthcare
Subiaco, Western Australia, 6008
The Queen Elizabeth Hospital
Woodville South, South Australia, 5011
Germany4 sites
Charite Universitaetsmedizin Berlin, Campus Virchow
Berlin, 13353
Universitatsklinikum Koln
Cologne, 50937
Universitaetsklinikum Dresden
Dresden, 01307
Universitaetsklinikum Essen
Essen, 45147
Taiwan4 sites
National Cheng Kung University Hospital
Tainan, 70403
National Taiwan University Hospital
Taipei, 10002
Taipei Veterans General Hospital
Taipei, 11217
Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
Taoyuan, 33305
Italy3 sites
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
Milan, 20162
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126
Centro Ricerche Cliniche Di Verona Societa responsabilita limitata
Verona, 37126
Japan3 sites
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Koto-ku, Tokyo, 135-8550
Aichi Cancer Center
Nagoya, Aichi-ken, 464-8681
South Korea3 sites
Seoul National University Hospital
Seoul, 03080
The Catholic University of Korea Seoul St Marys Hospital
Seoul, 06591
Asan Medical Center
Seoul, 138-736
Austria2 sites
Medizinische Universitaet Graz
Graz, 8036
Landeskrankenhaus Salzburg
Salzburg, 5020
Belgium2 sites
Universite Catholique de Louvain Cliniques Universitaires Saint Luc
Brussels, 1200
Universitair Ziekenhuis Antwerpen
Edegem, 2650
United Kingdom1 site
Sarah Cannon Research Institute UK
London, W1G 6AD
About this study
Official title: A Phase 1b, Protocol Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Sotorasib Monotherapy and in Combination With Other Anti-cancer Therapies in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors.
- Being tested
- Sotorasib, Trametinib, RMC-4630, Afatinib, Pembrolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SotorasibDrug
Sotorasib administered orally as a tablet.
TrametinibDrug
Trametinib administered orally as a tablet.
RMC-4630Drug
RMC-4630 administered orally as a capsule.
AfatinibDrug
afatinib administered orally as a tablet.
PembrolizumabDrug
pembrolizumab administered as an intravenous (IV) infusion.
PanitumumabDrug
Panitumumab administered as an IV infusion.
Carboplatin, pemetrexed, docetaxel, paclitaxelDrug
Carboplatin, pemetrexed, docetaxel administered as an IV infusion.
AtezolizumabDrug
Atezolizumab administered as an IV injection.
PalbociclibDrug
Palbociclib administered orally as a tablet.
MVASI® (bevacizumab-awwb)Drug
MVASI® (bevacizumab-awwb) administered as an IV infusion.
TNO155Drug
TNO155 administered orally as a capsule.
IV Chemotherapy (Regimen 1)Drug
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.
IV Chemotherapy (Regimen 2)Drug
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.
BI 1701963Drug
BI 1701963 administered orally
AMG 404Drug
AMG 404 administered as an IV infusion.
EverolimusDrug
Everolimus administered orally.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Sotorasib; Drug: Trametinib; Drug: 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. Receives: Drug: Sotorasib; Drug: 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. Receives: Drug: Sotorasib; Drug: 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. Receives: Drug: Sotorasib; Drug: Panitumumab; Drug: 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. Receives: Drug: Sotorasib; Drug: 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. Receives: Drug: Sotorasib; Drug: Pembrolizumab; Drug: 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. Receives: 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. Receives: Drug: Sotorasib; Drug: 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. Receives: Drug: Sotorasib; Drug: 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. Receives: Drug: Sotorasib; Drug: 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. Receives: Drug: Sotorasib; Drug: 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. Receives: Drug: Sotorasib; Drug: 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 Receives: Drug: Sotorasib; Drug: 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. Receives: Drug: Sotorasib; Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Dose Limiting Toxicities (DLTs)
Measured: 12 Months
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Measured: 12 Months
Number of Participants with Treatment-related Adverse Events
Measured: 12 Months
Number of Participants with Clinically Significant Changes in Vital Signs
Measured: 12 Months
Number of Participants with Clinically Significant Changes in ECG Measurements
Measured: 12 Months
Number of Participants with Clinically Significant Changes in Laboratory Test Values
Measured: 12 Months
Secondary outcomes (25)
Maximum Plasma Concentration (Cmax)
Measured: 12 Months
Time to Maximum Plasma Concentration (Tmax)
Measured: 12 Months
Area Under the Plasma Concentration-time Curve (AUC)
Measured: 12 Months
Objective Response Rate
Measured: 12 Months
Disease Control Rate
Measured: 12 Months
Duration of Response
Measured: 12 Months
Progression-free Survival
Measured: 12 Months
Duration of Stable Disease
Measured: 12 Months
Time to Response
Measured: 12 Months
Overall Survival
Measured: 12 Months
Sotorasib + EGFR Inhibitor +/- Chemotherapeutic Regimen Only: Quantification of Plasma Levels
Measured: 12 Months
Sotorasib Monotherapy Only: Intracranial Objective Response Rate
Intracranial objective response rate assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM).
Measured: 12 Months
Sotorasib Monotherapy Only: Intracranial Disease Control Rate
Intracranial disease control rate assessed per RANO-BM.
Measured: 12 Months
Sotorasib Monotherapy Only: Intracranial Duration of Response
Intracranial duration of response assessed per RANO-BM.
Measured: 12 Months
Sotorasib Monotherapy Only: Time to Intracranial Radiation Therapy
Measured: 12 Months
Sotorasib Monotherapy Only: Intracranial Progression-free Survival (PFS)
Intracranial PFS assessed per RANO-BM.
Measured: 12 Months
Sotorasib Monotherapy Only: Non-intracranial Progression-free Survival (PFS)
Non-intracranial PFS assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Measured: 12 Months
Sotorasib Monotherapy Only: Overall Progression-free Survival (PFS)
Overall PFS assessed per RECIST 1.1 and RANO-BM.
Measured: 12 Months
Sotorasib + TNO155 Only: Best Overall Response
Measured: 12 Months
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Dose Limiting Toxicities (DLTs)
Measured: 12 Months
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Measured: 12 Months
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-related Adverse Events
Measured: 12 Months
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Vital Signs
Measured: 12 Months
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in ECG Measurements
Measured: 12 Months
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Laboratory Test Values
Measured: 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2019
- Study start17 Dec 2019
- Primary completion17 Dec 2026 (estimated)
- Study completion5 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 610 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04185883
- Sponsor's protocol ID
- 20190135
- Other IDs
- 2023-506794-35, 2023
- Status last verified
- Oct 2025
- First submitted
- 3 Dec 2019
- Last updated
- 22 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
- Expanded access
- Available
Publications
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.
PubMed 38177853
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Protocol Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Sotorasib Monotherapy and in Combination With Other Anti-cancer Therapies in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
- ClinicalTrials.gov ID
- NCT04185883
- Acronym / sponsor ID
- 20190135
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 610 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 17 Dec 2019 (actual)
- Primary completion
- 17 Dec 2026 (estimated)
- Study completion
- 5 Dec 2027 (estimated)
- First posted
- 4 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 14
| Arm | Type | Receives |
|---|---|---|
| Sotorasib + trametinib + panitumumab | Experimental | Drug: Sotorasib, Drug: Trametinib, Drug: PanitumumabExperimental: 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. |
| Sotorasib + RMC-4630 | Experimental | Drug: Sotorasib, Drug: RMC-4630Experimental: 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. |
| Sotorasib + afatinib | Experimental | Drug: Sotorasib, Drug: AfatinibExperimental: 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. |
| Sotorasib + panitumumab +/- chemotherapy | Experimental | Drug: Sotorasib, Drug: Panitumumab, Drug: IV Chemotherapy (Regimen 1)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. |
| Sotorasib + atezolizumab | Experimental | Drug: Sotorasib, Drug: AtezolizumabExperimental: 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. |
| Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab | Experimental | Drug: Sotorasib, Drug: Pembrolizumab, Drug: Carboplatin, pemetrexed, docetaxel, paclitaxelExperimental: 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. |
| Sotorasib Monotherapy | Experimental | Drug: SotorasibExperimental: 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. |
| Sotorasib + palbociclib | Experimental | Drug: Sotorasib, Drug: PalbociclibExperimental: 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. |
| Sotorasib + pembrolizumab | Experimental | Drug: Sotorasib, Drug: PembrolizumabExperimental: 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. |
| Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy | Experimental | Drug: Sotorasib, Drug: MVASI® (bevacizumab-awwb), Drug: IV Chemotherapy (Regimen 1), Drug: IV Chemotherapy (Regimen 2)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. |
| Sotorasib + TNO155 | Experimental | Drug: Sotorasib, Drug: TNO155Experimental: 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. |
| Sotorasib + BI 1701963 | Experimental | Drug: Sotorasib, Drug: BI 1701963Experimental: 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. |
| Sotorasib + AMG 404 | Experimental | Drug: Sotorasib, Drug: AMG 404Experimental: 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 |
| Sotorasib + everolimus | Experimental | Drug: Sotorasib, Drug: EverolimusExperimental: 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SotorasibSotorasib administered orally as a tablet. | Drug | Sotorasib + AMG 404, Sotorasib + BI 1701963, Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy, Sotorasib + RMC-4630, Sotorasib + TNO155, Sotorasib + afatinib, Sotorasib + atezolizumab, Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab, Sotorasib + everolimus, Sotorasib + palbociclib, Sotorasib + panitumumab +/- chemotherapy, Sotorasib + pembrolizumab, Sotorasib + trametinib + panitumumab, Sotorasib Monotherapy |
| TrametinibTrametinib administered orally as a tablet. | Drug | Sotorasib + trametinib + panitumumab |
| RMC-4630RMC-4630 administered orally as a capsule. | Drug | Sotorasib + RMC-4630 |
| Afatinibafatinib administered orally as a tablet. | Drug | Sotorasib + afatinib |
| Pembrolizumabpembrolizumab administered as an intravenous (IV) infusion. | Drug | Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab, Sotorasib + pembrolizumab |
| PanitumumabPanitumumab administered as an IV infusion. | Drug | Sotorasib + panitumumab +/- chemotherapy, Sotorasib + trametinib + panitumumab |
| Carboplatin, pemetrexed, docetaxel, paclitaxelCarboplatin, pemetrexed, docetaxel administered as an IV infusion. | Drug | Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab |
| AtezolizumabAtezolizumab administered as an IV injection. | Drug | Sotorasib + atezolizumab |
| PalbociclibPalbociclib administered orally as a tablet. | Drug | Sotorasib + palbociclib |
| MVASI® (bevacizumab-awwb)MVASI® (bevacizumab-awwb) administered as an IV infusion. | Drug | Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy |
| TNO155TNO155 administered orally as a capsule. | Drug | Sotorasib + TNO155 |
| IV Chemotherapy (Regimen 1)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. | Drug | Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy, Sotorasib + panitumumab +/- chemotherapy |
| IV Chemotherapy (Regimen 2)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. | Drug | Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy |
| BI 1701963BI 1701963 administered orally | Drug | Sotorasib + BI 1701963 |
| AMG 404AMG 404 administered as an IV infusion. | Drug | Sotorasib + AMG 404 |
| EverolimusEverolimus administered orally. | Drug | Sotorasib + everolimus |
Primary outcome
Number of Participants with Dose Limiting Toxicities (DLTs)
Time frame: 12 Months
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Time frame: 12 Months
Number of Participants with Treatment-related Adverse Events
Time frame: 12 Months
Number of Participants with Clinically Significant Changes in Vital Signs
Time frame: 12 Months
Number of Participants with Clinically Significant Changes in ECG Measurements
Time frame: 12 Months
Number of Participants with Clinically Significant Changes in Laboratory Test Values
Time frame: 12 Months
25 secondary outcomes
Maximum Plasma Concentration (Cmax)
Time frame: 12 Months
Time to Maximum Plasma Concentration (Tmax)
Time frame: 12 Months
Area Under the Plasma Concentration-time Curve (AUC)
Time frame: 12 Months
Objective Response Rate
Time frame: 12 Months
Disease Control Rate
Time frame: 12 Months
Duration of Response
Time frame: 12 Months
Progression-free Survival
Time frame: 12 Months
Duration of Stable Disease
Time frame: 12 Months
Time to Response
Time frame: 12 Months
Overall Survival
Time frame: 12 Months
Sotorasib + EGFR Inhibitor +/- Chemotherapeutic Regimen Only: Quantification of Plasma Levels
Time frame: 12 Months
Sotorasib Monotherapy Only: Intracranial Objective Response Rate
Time frame: 12 Months
Sotorasib Monotherapy Only: Intracranial Disease Control Rate
Time frame: 12 Months
Sotorasib Monotherapy Only: Intracranial Duration of Response
Time frame: 12 Months
Sotorasib Monotherapy Only: Time to Intracranial Radiation Therapy
Time frame: 12 Months
Sotorasib Monotherapy Only: Intracranial Progression-free Survival (PFS)
Time frame: 12 Months
Sotorasib Monotherapy Only: Non-intracranial Progression-free Survival (PFS)
Time frame: 12 Months
Sotorasib Monotherapy Only: Overall Progression-free Survival (PFS)
Time frame: 12 Months
Sotorasib + TNO155 Only: Best Overall Response
Time frame: 12 Months
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Dose Limiting Toxicities (DLTs)
Time frame: 12 Months
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Time frame: 12 Months
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-related Adverse Events
Time frame: 12 Months
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Vital Signs
Time frame: 12 Months
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in ECG Measurements
Time frame: 12 Months
Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Laboratory Test Values
Time frame: 12 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2025.
- Background: PubMed 38177853Kuboki 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
90 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sotorasib, Trametinib and RMC-4630 in people with Advanced Solid Tumors and Kirsten Rat Sarcoma (KRAS) pG12C Mutation, run by Amgen at 90 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 90 sites in United States, Spain, Australia, Germany, Taiwan and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Dose Limiting Toxicities (DLTs) (time frame: 12 Months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04185883, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2025.