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)

Amgen

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: KRAS p.G12C Mutant Advanced Solid Tumors

Treatments: Drug: Anti PD-1/L1; Drug: sotorasib; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT03600883

20170543

Details and patient eligibility

About

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.

Enrollment: 713 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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713 participants in 6 patient groups

Phase 1 Dose Exploration Part 1 monotherapy

Experimental group

Description:

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

Treatment:

Drug: sotorasib

Phase 1 Dose Expansion Part 2 monotherapy

Experimental group

Description:

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

Treatment:

Drug: sotorasib

Phase 1 combination arm with sotorasib and anti PD-1/L1

Experimental group

Description:

Additional subjects will be enrolled into the combination arm with sotorasib in combination with an anti (PD-1/L1)

Treatment:

Drug: sotorasib

Drug: Anti PD-1/L1

Phase 1 monotherapy treatment naive advanced NSCLC

Experimental group

Description:

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.

Treatment:

Drug: Midazolam

Drug: sotorasib

Phase 2 monotherapy dose comparison

Experimental group

Description:

Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy

Treatment:

Drug: sotorasib

Phase 1 Does escalation and Expansion monotherapy BID

Experimental group

Description:

BID 2L+solid tumors (fed state)

Treatment:

Drug: sotorasib