NCT03600883 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2026-06-30

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility 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.
healthy Volunteers: false
maximum Age: 100 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

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
intervention Names
Drug: sotorasib
label
Phase 1 Dose Exploration Part 1 monotherapy
type
EXPERIMENTAL
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
intervention Names
Drug: sotorasib
label
Phase 1 Dose Expansion Part 2 monotherapy
type
EXPERIMENTAL
description
Additional subjects will be enrolled into the combination arm with sotorasib in combination with an anti (PD-1/L1)
intervention Names
Drug: sotorasib
Drug: Anti PD-1/L1
label
Phase 1 combination arm with sotorasib and anti PD-1/L1
type
EXPERIMENTAL
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.
intervention Names
Drug: sotorasib
Drug: Midazolam
label
Phase 1 monotherapy treatment naive advanced NSCLC
type
EXPERIMENTAL
description
Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy
intervention Names
Drug: sotorasib
label
Phase 2 monotherapy dose comparison
type
EXPERIMENTAL
description
BID 2L+solid tumors (fed state)
intervention Names
Drug: sotorasib
label
Phase 1 Does escalation and Expansion monotherapy BID
type
EXPERIMENTAL

interventions

arm Group Labels
Phase 1 Does escalation and Expansion monotherapy BID
Phase 1 Dose Expansion Part 2 monotherapy
Phase 1 Dose Exploration Part 1 monotherapy
Phase 1 combination arm with sotorasib and anti PD-1/L1
Phase 1 monotherapy treatment naive advanced NSCLC
Phase 2 monotherapy dose comparison
description
Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
name
sotorasib
type
DRUG
arm Group Labels
Phase 1 combination arm with sotorasib and anti PD-1/L1
description
Administered as an intravenous (IV) infusion
name
Anti PD-1/L1
type
DRUG
arm Group Labels
Phase 1 monotherapy treatment naive advanced NSCLC
description
Administered as an oral hydrochloride (HCI) syrup
name
Midazolam
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

SEQUENTIAL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 713
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Treatment-emergent adverse events will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC * Phase 2 monotherapy dose comparison
measure
Primary: Number of subjects with treatment-emergent adverse events
time Frame
24 Months
description
Treatment-related adverse events will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC
measure
Primary: Number of subjects with treatment-related adverse events
time Frame
24 Months
description
Grade ≥3 treatment-emergent adverse events will be a primary outcome measure in the following group: \- Phase 2 monotherapy dose comparison
measure
Primary: Number of subjects with grade ≥3 treatment-emergent adverse events
time Frame
24 Months
description
Serious adverse events will be a primary outcome measure in the following group: \- Phase 2 monotherapy dose comparison
measure
Primary: Number of subjects with serious adverse events
time Frame
24 Months
description
Adverse events of interest will be a primary outcome measure in the following group: \- Phase 2 monotherapy dose comparison
measure
Primary: Number of subjects with adverse events of interest
time Frame
24 Months
description
Vital signs will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC
measure
Primary: Number of subjects with clinically significant changes in vital signs
time Frame
Baseline to 24 Months
description
Physical examinations will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1
measure
Primary: Number of subjects with clinically significant changes in physical examination results
time Frame
Baseline to 24 Months
description
ECGs will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC
measure
Primary: Number of subjects with clinically significant changes on electrocardiograms (ECGs)
time Frame
Baseline to 24 Months
description
Abnormal clinical laboratory values will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC
measure
Primary: Number of subjects with clinically significant changes in clinical laboratory values
time Frame
Baseline to 24 Months
description
DLTs will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC
measure
Primary: Number of subjects with dose-limiting toxicities (DLTs)
time Frame
21 Days
description
ORR will be a primary outcome measure in the following group: * Phase 1 monotherapy treatment naïve advanced NSCLC * Phase 2 monotherapy * Phase 2 monotherapy dose comparison
measure
Primary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria
time Frame
24 Months
description
DOR will be a primary outcome measure in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC
measure
Primary: Duration of response (DOR) as assessed by RECIST 1.1 criteria
time Frame
24 Months

secondary Outcomes

description
Cmax will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC * Phase 2 monotherapy dose comparison
measure
Secondary: Plasma concentration (Cmax) of sotorasib
time Frame
15 Weeks
description
Cmax of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC
measure
Secondary: Plasma concentration (Cmax) of midazolam
time Frame
16 Days
description
Tmax will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC
measure
Secondary: Time to achieve Cmax (Tmax) of sotorasib
time Frame
15 Weeks
description
AUC will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC * Phase 2 monotherapy dose comparison
measure
Secondary: Area under the plasma concentration-time curve (AUC) of sotorasib
time Frame
15 Weeks
description
AUC of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC
measure
Secondary: Area under the plasma concentration-time curve (AUC) of midazolam
time Frame
16 Days
description
Clearance of midazolam from the plasma will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC
measure
Secondary: Clearance of midazolam from the plasma
time Frame
16 Days
description
t1/2 of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC
measure
Secondary: Terminal half-life (t1/2) of midazolam
time Frame
16 Days
description
ORR will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1
measure
Secondary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria
time Frame
24 Months
description
DOR will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 2 monotherapy dose comparison
measure
Secondary: Duration of response (DOR) as assessed by RECIST 1.1 criteria
time Frame
24 Months
description
DOR will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 2 monotherapy dose comparison
measure
Secondary: Disease control as assessed by RECIST 1.1 criteria
time Frame
24 Months
description
PFS will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 2 monotherapy dose comparison * Phase 1 monotherapy treatment naïve advanced NSCLC
measure
Secondary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria
time Frame
24 Months
description
Duration of SD will be a secondary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1
measure
Secondary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria
time Frame
24 Months

Full study description

brief Summary: 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.

Source references

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