Protocol Summary

Protocol No.: OCR24302

Sponsor Protocol No.: 20170543; 20170543;AMG510; P0136845

Protocol Title.: 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)

Principal Investigator: George, Thomas

Objective: 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.

Phase: Phase I/II

Age Group: Adult

Age: 18 Years - 100 Years

Gender: All

Scope: National


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

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

Experimental: Phase 2 monotherapy
Additional subjects will be enrolled in the dose expansion to confirm the recommended phase 2 dose. Enrollment into phase 2 will be opened after confirmation of the recommended phase 2 dose

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)

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.

Experimental: Phase 2 monotherapy dose comparison
Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy

Detailed Eligibility:

Inclusion Criteria: - Men or women greater than or equal to 18 years old. - Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing. Exclusion Criteria - Active brain metastases from non-brain tumors. - Myocardial infarction within 6 months of study day 1. - Gastrointestinal (GI) tract disease causing the inability to take oral medication.

Applicable Conditions:

  • Anus
  • Bones and Joints
  • Brain and Nervous System
  • Breast
  • Cervix
  • Colon
  • Corpus Uteri
  • Esophagus
  • Eye and Orbit
  • Ill-Defined Sites
  • Kidney
  • Larynx
  • Lip, Oral Cavity and Pharynx
  • Liver
  • Lung
  • Melanoma, Skin
  • Other Digestive Organ
  • Other Endocrine System
  • Other Male Genital
  • Other Respiratory and Intrathoracic Organs
  • Other Skin
  • Other Urinary
  • Ovary
  • Pancreas
  • Prostate
  • Rectum
  • Small Intestine
  • Soft Tissue
  • Stomach
  • Thyroid
  • Unknown Sites
  • Urinary Bladder
  • Participation Institution:

  • No UF Health MRN : Daniela Skiff
  • UF Gainesville : Daniela Skiff
  • Contact:
    Daniela Skiff

    More Information: View study listing on