Clinical Trial: NCT03600883 - My Cancer Genome

NCT03600883

Description:

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.

Related Conditions:

Malignant Solid Tumor
Non-Small Cell Lung Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT03600883

Trial Eligibility

Document

Title

Brief Title: A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)
Official Title: A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 510 Monotherapy in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation and AMG 510 Combination Therapy in Subjects With Advanced NSCLC With KRAS p.G12C Mutation (CodeBreaK 100)

Clinical Trial IDs

ORG STUDY ID: 20170543
NCT ID: NCT03600883

Conditions

KRAS p.G12C Mutant Advanced Solid Tumors

Interventions

Drug	Synonyms	Arms
AMG 510		Phase 1 Dose Expansion Part 2 monotherapy
Anti PD-1/L1		Phase 1 combination arm with AMG 510 and anti PD-1/L1
Midazolam		Phase 1 monotherapy treatment naive advanced NSCLC

Purpose

Trial Arms

Name	Type	Description	Interventions
Phase 1 Dose Exploration Part 1 monotherapy	Experimental	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	AMG 510
Phase 1 Dose Expansion Part 2 monotherapy	Experimental	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	AMG 510
Phase 2 monotherapy	Experimental	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	AMG 510
Phase 1 combination arm with AMG 510 and anti PD-1/L1	Experimental	Additional subjects will be enrolled into the combination arm with AMG 510 in combination with an anti (PD-1/L1)	AMG 510 Anti PD-1/L1
Phase 1 monotherapy treatment naive advanced NSCLC	Experimental	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.	AMG 510 Midazolam
Phase 2 monotherapy dose comparison	Experimental	Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy	AMG 510

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.

Maximum Eligible Age:	100 Years
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Primary: Number of subjects with treatment-emergent adverse events
Time Frame:	24 Months
Safety Issue:
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 AMG 510 and anti PD-1/L1 Phase 1 monotherapy treatment naïve advanced NSCLC Phase 2 monotherapy dose comparison

Secondary Outcome Measures

Measure:	Secondary: Plasma concentration (Cmax) of AMG 510
Time Frame:	24 Months
Safety Issue:
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 AMG 510 and anti PD-1/L1 Phase 1 monotherapy treatment naïve advanced NSCLC Phase 2 monotherapy dose comparison

Measure:	Secondary: Plasma concentration (Cmax) of midazolam
Time Frame:	16 Days
Safety Issue:
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: Time to achieve Cmax (Tmax) of AMG 510
Time Frame:	24 Months
Safety Issue:
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 AMG 510 and anti PD-1/L1 Phase 1 monotherapy treatment naïve advanced NSCLC

Measure:	Secondary: Area under the plasma concentration-time curve (AUC) of AMG 510
Time Frame:	24 Months
Safety Issue:
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 AMG 510 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 midazolam
Time Frame:	16 Days
Safety Issue:
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: Clearance of midazolam from the plasma
Time Frame:	16 Days
Safety Issue:
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: Terminal half-life (t1/2) of midazolam
Time Frame:	16 Days
Safety Issue:
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: Objective response rate (ORR) as assessed by RECIST 1.1 criteria
Time Frame:	24 Months
Safety Issue:
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 AMG 510 and anti PD-1/L1

Measure:	Secondary: Duration of response (DOR) as assessed by RECIST 1.1 criteria
Time Frame:	24 Months
Safety Issue:
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 AMG 510 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
Safety Issue:
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 AMG 510 and anti PD-1/L1 Phase 2 monotherapy dose comparison

Measure:	Secondary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria
Time Frame:	24 Months
Safety Issue:
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 AMG 510 and anti PD-1/L1 Phase 2 monotherapy dose comparison

Measure:	Secondary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria
Time Frame:	24 Months
Safety Issue:
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 AMG 510 and anti PD-1/L1

Measure:	Secondary: Depth of response (best percentage change from baseline in lesion sum diameters) as assessed by RECIST 1.1 criteria
Time Frame:	Baseline to 24 Months
Safety Issue:
Description:	Depth of response will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison

Measure:	Secondary: Time to response (TTR) as assessed by RECIST 1.1 criteria
Time Frame:	24 Months
Safety Issue:
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 AMG 510 and anti PD-1/L1 Phase 2 monotherapy dose comparison

Measure:	Secondary: Overall survival (OS)
Time Frame:	24 Months
Safety Issue:
Description:	OS 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 AMG 510 and anti PD-1/L1 Phase 2 monotherapy dose comparison

Measure:	Secondary: AMG 510 exposure and QTc interval relationship
Time Frame:	24 Months
Safety Issue:
Description:	AMG 510 exposure and QTc interval relationship will be a secondary outcome measure for the following groups: Phase 1 Dose Exploration Part 1 monotherapy Phase 1 Dose Expansion Part 2 monotherapy

Measure:	Secondary: Progression-free survival (PFS) at 6 months
Time Frame:	6 Months
Safety Issue:
Description:	PFS at 6 months will be a secondary outcome measure for the following group: - Phase 2 monotherapy

Measure:	Secondary: Progression-free survival (PFS) at 12 months
Time Frame:	12 Months
Safety Issue:
Description:	PFS at 12 months will be a secondary outcome measure for the following group: - Phase 2 monotherapy

Measure:	Secondary: Overall survival (OS) at 12 months
Time Frame:	12 Months
Safety Issue:
Description:	OS at 12 months will be a secondary outcome measure for the following group: - Phase 2 monotherapy

Measure:	Secondary: Number of subjects with treatment-emergent adverse events
Time Frame:	24 Months
Safety Issue:
Description:	Treatment-emergent adverse events will be a secondary outcome measure for the following group: - Phase 2 monotherapy

Measure:	Secondary: Number of subjects with grade ≥3 treatment-emergent adverse events
Time Frame:	24 Months
Safety Issue:
Description:	Grade ≥3 treatment-emergent adverse events will be a secondary outcome measure for the following group: - Phase 2 monotherapy

Measure:	Secondary: Impact of treatment on disease-related symptoms and health related quality of life (HRQOL) as assessed by EORTC QLQ-C30
Time Frame:	24 Months
Safety Issue:
Description:	Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison

Measure:	Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by disease-specific modules Quality-of-Life Questionnaire Lung Cancer Module (QLQ LC13)
Time Frame:	24 Months
Safety Issue:
Description:	Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison

Measure:	Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by non-small cell lung cancer symptom assessment questionnaire (NSCLC SAQ) for NSCLC
Time Frame:	24 Months
Safety Issue:
Description:	Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison

Measure:	Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Severity (PGIS)
Time Frame:	24 Months
Safety Issue:
Description:	Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison

Measure:	Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Change (PGIC) in cough, dyspnea and chest pain for NSCLC
Time Frame:	24 Months
Safety Issue:
Description:	Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison

Measure:	Secondary: Treatment-related symptoms and impact on the subject as assessed by EORTC QLQ-C30
Time Frame:	24 Months
Safety Issue:
Description:	Treament related symptoms and impact on the subject will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison

Measure:	Secondary: Treatment-related symptoms and impact on the subject as assessed by selected questions from the Patient-reported Outcome of the Common Terminology Criteria for Adverse Events (PRO-CTCAE library)
Time Frame:	24 Months
Safety Issue:
Description:	Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison

Measure:	Secondary: Treatment-related symptoms and impact on the subject as assessed by a single item about symptom bother, item GP5 of the Functional Assessment of Cancer Therapy - General (FACT-G)
Time Frame:	24 Months
Safety Issue:
Description:	Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison

Measure:	Secondary: Change from baseline in physical function as assessed by EORTC QLQ-C30
Time Frame:	Baseline to 24 Months
Safety Issue:
Description:	Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group: - Phase 2 monotherapy dose comparison

Details

Phase:	Phase 1/Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Amgen

Last Updated

August 12, 2021

Clinical Trials /

A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)