Purpose

Evaluate the safety and tolerability of AMG 510 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.

Condition

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.

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 Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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: AMG 510
    Characterize the pharmacokinetics (PK) of AMG 510 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: AMG 510
    Characterize the pharmacokinetics (PK) of AMG 510 following administration as an oral Tablet formulation
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
  • Drug: AMG 510
    Characterize the pharmacokinetics (PK) of AMG 510 following administration as an oral Tablet formulation
Experimental
Phase 1 combination arm with AMG 510 and anti PD-1/L1
Additional subjects will be enrolled into the combination arm with AMG 510 in combination with an anti (PD-1/L1)
  • Drug: AMG 510
    Characterize the pharmacokinetics (PK) of AMG 510 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 AMG 510 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 AMG 510 on Day 15 of Cycle 1, where each cycle is 21 days.
  • Drug: AMG 510
    Characterize the pharmacokinetics (PK) of AMG 510 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: AMG 510
    Characterize the pharmacokinetics (PK) of AMG 510 following administration as an oral Tablet formulation

Recruiting Locations

Vanderbilt University Ingram Cancer Center
Nashville, Tennessee 37232

More Details

Status
Recruiting
Sponsor
Amgen

Study Contact

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.