Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)

Purpose

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

Conditions

  • Advanced Solid Tumors
  • Kirsten Rat Sarcoma (KRAS) pG12C Mutation

Eligibility

Eligible Ages
Between 18 Years and 100 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Exclusion Criteria

  • 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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Sotorasib + trametinib + panitumumab 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: Trametinib
    Trametinib administered orally as a tablet.
  • Drug: Panitumumab
    Panitumumab administered as an IV infusion.
Experimental
Sotorasib + RMC-4630 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: RMC-4630
    RMC-4630 administered orally as a capsule.
Experimental
Sotorasib + afatinib 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: Afatinib
    afatinib administered orally as a tablet.
Experimental
Sotorasib + panitumumab +/- chemotherapy 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: Panitumumab
    Panitumumab administered as an IV infusion.
  • Drug: 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.
Experimental
Sotorasib + atezolizumab 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: Atezolizumab
    Atezolizumab administered as an IV injection.
Experimental
Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: Pembrolizumab
    pembrolizumab administered as an intravenous (IV) infusion.
  • Drug: Carboplatin, pemetrexed, docetaxel, paclitaxel
    Carboplatin, pemetrexed, docetaxel administered as an IV infusion.
Experimental
Sotorasib Monotherapy 		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 administered orally as a tablet.
Experimental
Sotorasib + palbociclib 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: Palbociclib
    Palbociclib administered orally as a tablet.
Experimental
Sotorasib + pembrolizumab 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: Pembrolizumab
    pembrolizumab administered as an intravenous (IV) infusion.
Experimental
Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: MVASI® (bevacizumab-awwb)
    MVASI® (bevacizumab-awwb) administered as an IV infusion.
  • Drug: 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: 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.
Experimental
Sotorasib + TNO155 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: TNO155
    TNO155 administered orally as a capsule.
Experimental
Sotorasib + BI 1701963 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: BI 1701963
    BI 1701963 administered orally
Experimental
Sotorasib + AMG 404 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: AMG 404
    AMG 404 administered as an IV infusion.
Experimental
Sotorasib + everolimus 		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: Sotorasib
    Sotorasib administered orally as a tablet.
  • Drug: Everolimus
    Everolimus administered orally.

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232

More Details

Status
Recruiting
Sponsor
Amgen

Study Contact

Amgen Call Center
866-572-6436
medinfo@amgen.com

For general questions about clinical trials, contact Research Support Services at (615) 322-7343 or research.support.services@vumc.org