Vanderbilt Clinical Trials

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)

Purpose

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.

Condition

KRAS p.G12C Mutant Advanced Solid Tumors

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

Arm	Description	Assigned 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: sotorasib Characterize the pharmacokinetics (PK) of sotorasib 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: sotorasib Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
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)	Drug: sotorasib Characterize the pharmacokinetics (PK) of sotorasib 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 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.	Drug: sotorasib Characterize the pharmacokinetics (PK) of sotorasib 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: sotorasib Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Experimental Phase 1 Does escalation and Expansion monotherapy BID	BID 2L+solid tumors (fed state)	Drug: sotorasib Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation

More Details

Status: Active, not recruiting
Sponsor: Amgen

Study Contact

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.