202200050434: Combination Therapies With Adagrasib in Patients With Advanced NSCLC With KRAS G12C Mutation

Sponsor

Mirati Therapeutics Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05609578

Collaborator

(none)

Enrollment

Locations

Arms

40.8

Anticipated Duration (Months)

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study 849-017 is an open-label, Phase 2 clinical trial evaluating the clinical efficacy of combination therapies with adagrasib in patients with advanced NSCLC with TPS ≥ 1% and KRAS G12C mutation

Condition or Disease	Intervention/Treatment	Phase
Advanced NSCLC Metastatic Lung Cancer	Drug: Adagrasib in combination with pembrolizumab Biological: Pembrolizumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Trial of Combination Therapies With Adagrasib in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

Actual Study Start Date :

Jul 29, 2022

Anticipated Primary Completion Date :

Jun 23, 2025

Anticipated Study Completion Date :

Dec 23, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: PD-L1 TPS≥ 1% Adagrasib 400mg twice daily (BID) x 2 cycles followed by adagrasib 400mg BID in combination with pembrolizumab	Drug: Adagrasib in combination with pembrolizumab Adagrasib will be administered orally twice daily in a continuous regimen Biological: Pembrolizumab Pembrolizumab will be administered as an intravenous infusion once every 3 weeks
Experimental: Cohort B: PD-L1 TPS≥ 1% Adagrasib 600mg twice daily (BID) x 2 cycles followed by adagrasib 400mg BID in combination with pembrolizumab	Drug: Adagrasib in combination with pembrolizumab Adagrasib will be administered orally twice daily in a continuous regimen Biological: Pembrolizumab Pembrolizumab will be administered as an intravenous infusion once every 3 weeks

Arm

Intervention/Treatment

Experimental: Cohort A: PD-L1 TPS≥ 1%

Adagrasib 400mg twice daily (BID) x 2 cycles followed by adagrasib 400mg BID in combination with pembrolizumab

Drug: Adagrasib in combination with pembrolizumab

Adagrasib will be administered orally twice daily in a continuous regimen

Biological: Pembrolizumab

Pembrolizumab will be administered as an intravenous infusion once every 3 weeks

Experimental: Cohort B: PD-L1 TPS≥ 1%

Adagrasib 600mg twice daily (BID) x 2 cycles followed by adagrasib 400mg BID in combination with pembrolizumab

Drug: Adagrasib in combination with pembrolizumab

Adagrasib will be administered orally twice daily in a continuous regimen

Biological: Pembrolizumab

Pembrolizumab will be administered as an intravenous infusion once every 3 weeks

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) [30 months]
Defined as the percent of patients documented to have a confirmed CR or PR

Secondary Outcome Measures

Adverse Events [30 months]
Defined as number of patients with treatment emergent AEs
Duration of Response (DOR) [30 months]
Defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either Progression of Disease (PD) or death due to any cause, whichever occurs first.
Progression-free Survival (PFS) [30 months]
Defined as time from randomization until disease progression or death from any cause, whichever occurs first.
Overall Survival (OS) [30 months]
Defined as time from date of randomization to date of death due to any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnosis of unresectable or metastatic NSCLC (squamous or nonsquamous) with KRAS G12C mutation and PD-L1 TPS ≥ 1%

Exclusion Criteria:

Prior systemic treatment for locally advanced or metastatic NSCLC, including chemotherapy, immune checkpoint inhibitor therapy (CIT), or any therapy targeting KRAS G12C mutation (eg, sotorasib)
Radiation to the lung ≥ 30 Gy within 6 months prior to first dose of study treatment
Active brain metastases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hematology Oncology Associates of CNY, PC	East Syracuse	New York	United States	13057
2	Cleveland Clinic	Cleveland	Ohio	United States	44195
3	PeaceHealth St. Joseph Medical Center	Bellingham	Washington	United States	98225