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

Primary Purpose

Advanced NSCLC, Metastatic Lung Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Adagrasib oral dose of 400 mg twice daily tablets
Pembrolizumab
Chemotherapy: Pemetrexed
Cisplatin/Carboplatin
Sponsored by
Mirati Therapeutics Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced NSCLC focused on measuring KRAS G12C, NSCLC, Non Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Cohort A* (closed): Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (squamous or nonsquamous) KRASG12C mutation and histologically confirmed PD-L1 TPS ≥1%. Cohort C: Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (non-squamous only) KRASG12C mutation and histologically confirmed PD-L1 TPS < 50% AND previously completed 4 cycles of standard-of-care platinum based induction chemotherapy with pembrolizumab AND experienced stable disease, partial response, or complete response per investigator's assessment after 4 cycles OR if patients received <4 cycles of a platinum-based induction, was stopped early due to intolerable toxicity Cohort E: Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (non-squamous only) KRASG12C mutation and histologically confirmed PD-L1 TPS < 50% Presence of measurable disease per RECIST v1.1 Exclusion Criteria: All Cohorts: Any prior therapy targeting KRASG12C mutation in any setting Cohorts A & E: Prior systemic therapy for locally advanced or metastatic NSCLC, including chemotherapy, immune checkpoint inhibitor therapy or chemoimmunotherapy (note: prior systemic therapy or chemoradiation given in the adjuvant or neoadjuvant setting are allowed if last dose of prior systemic treatment was >1 year prior to first dose of study treatment) Cohort C: received maintenance therapy (e.g, pembrolizumab and/or pemetrexed following completion of 4-6 cycles of a platinum-based regimen administered in the first-line setting Radiation to the lung > 30 Gy within 6 months prior to first dose of study treatment Active brain metastases

Sites / Locations

  • MemorialCare - Orange Coast Medical CenterRecruiting
  • MemorialCare - OC Blood and Cancer CenterRecruiting
  • USOR - Rocky Mountain Cancer Centers - Denver - Rose Medical Center CampusRecruiting
  • The Oncology Institute of Hope and InnovationRecruiting
  • UKCC - Westwood/Richard and Annette Bloch Cancer Care PavilionRecruiting
  • Henry Ford Cancer InstituteRecruiting
  • Mayo ClinicRecruiting
  • Hematology Oncology Associates of CNY, PCRecruiting
  • New York Cancer & Blood SpecialistsRecruiting
  • Cleveland ClinicRecruiting
  • Texas Oncology NortheastRecruiting
  • Texas Oncology - Baylor Charles A. Sammons Cancer CenterRecruiting
  • NEXT VirginiaRecruiting
  • PeaceHealth St. Joseph Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort A: PD-L1 TPS≥ 1% (Closed)

Cohort C

Cohort E

Arm Description

Adagrasib 400 mg BID for 2 cycles followed by adagrasib 400 mg BID + pembrolizumab 200 mg every 3 weeks (Q3W) up to 35 cycles

Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles

Adagrasib 400 mg BID + pembrolizumab 200 mg Q3W + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 Q3W OR carboplatin AUC 5 Q3W for 4 cycles, followed by adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W (up to 31 cycles)

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR) for Cohort A and E
Defined as the percent of patients documented to have a confirmed CR or PR
Progression-free Survival (PFS) at six months for Cohort C
PFS is defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.

Secondary Outcome Measures

Adverse Events
Defined as number of patients with treatment emergent AEs
Duration of Response (DOR)
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.
Overall Survival (OS)
Defined as time from date of first study treatment to date of death due to any cause
Progression-free Survival (PFS)
Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Population pharmacokinetic (PK) Model Derived AUC at Steady State (AUCtau,ss).
Concentration data from this study will be pooled with other studies and exposure parameters derived using population PK methods. Data for this Outcome Measure will not be reported here since ClinicalTrials.gov is designed to report results from participants enrolled in the study and described in the Participant Flow module.
Cohorts C and E: DLTs during SLI (Safety Lead In)
Defined as those patients in the SLI of the study who have received at least 80% of the assigned dose of adagrasib during the first cycle on study, or interrupted or discontinued study treatment during the first cycle due to a DLT.

Full Information

First Posted
November 1, 2022
Last Updated
October 5, 2023
Sponsor
Mirati Therapeutics Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05609578
Brief Title
Combination Therapies With Adagrasib in Patients With Advanced NSCLC With KRAS G12C Mutation
Official Title
A Phase 2 Trial of Combination Therapies With Adagrasib in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 29, 2022 (Actual)
Primary Completion Date
June 1, 2026 (Anticipated)
Study Completion Date
December 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mirati Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Study 849-017 is an open-label, Phase 2 clinical trial evaluating the clinical efficacy of adagrasib in combination with pembrolizumab and chemotherapy in the first-line setting for patients with advanced NSCLC with TPS ≥ 1%, TPS <50% and KRAS G12C mutation

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced NSCLC, Metastatic Lung Cancer
Keywords
KRAS G12C, NSCLC, Non Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort A: PD-L1 TPS≥ 1% (Closed)
Arm Type
Experimental
Arm Description
Adagrasib 400 mg BID for 2 cycles followed by adagrasib 400 mg BID + pembrolizumab 200 mg every 3 weeks (Q3W) up to 35 cycles
Arm Title
Cohort C
Arm Type
Experimental
Arm Description
Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles
Arm Title
Cohort E
Arm Type
Experimental
Arm Description
Adagrasib 400 mg BID + pembrolizumab 200 mg Q3W + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 Q3W OR carboplatin AUC 5 Q3W for 4 cycles, followed by adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W (up to 31 cycles)
Intervention Type
Drug
Intervention Name(s)
Adagrasib oral dose of 400 mg twice daily tablets
Intervention Description
oral dose of 400 mg twice daily tablets
Intervention Type
Combination Product
Intervention Name(s)
Pembrolizumab
Intervention Description
IV infusion once every 3 weeks
Intervention Type
Combination Product
Intervention Name(s)
Chemotherapy: Pemetrexed
Intervention Description
IV infusion once every 3 weeks
Intervention Type
Combination Product
Intervention Name(s)
Cisplatin/Carboplatin
Intervention Description
IV infusion once every 3 weeks
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) for Cohort A and E
Description
Defined as the percent of patients documented to have a confirmed CR or PR
Time Frame
30 months
Title
Progression-free Survival (PFS) at six months for Cohort C
Description
PFS is defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Time Frame
30 months
Secondary Outcome Measure Information:
Title
Adverse Events
Description
Defined as number of patients with treatment emergent AEs
Time Frame
30 months
Title
Duration of Response (DOR)
Description
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.
Time Frame
30 months
Title
Overall Survival (OS)
Description
Defined as time from date of first study treatment to date of death due to any cause
Time Frame
30 months
Title
Progression-free Survival (PFS)
Description
Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Time Frame
30 months
Title
Population pharmacokinetic (PK) Model Derived AUC at Steady State (AUCtau,ss).
Description
Concentration data from this study will be pooled with other studies and exposure parameters derived using population PK methods. Data for this Outcome Measure will not be reported here since ClinicalTrials.gov is designed to report results from participants enrolled in the study and described in the Participant Flow module.
Time Frame
Time Frame: Pre-dose and 4-6 hours post dose; up to 6 months
Title
Cohorts C and E: DLTs during SLI (Safety Lead In)
Description
Defined as those patients in the SLI of the study who have received at least 80% of the assigned dose of adagrasib during the first cycle on study, or interrupted or discontinued study treatment during the first cycle due to a DLT.
Time Frame
30 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Cohort A* (closed): Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (squamous or nonsquamous) KRASG12C mutation and histologically confirmed PD-L1 TPS ≥1%. Cohort C: Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (non-squamous only) KRASG12C mutation and histologically confirmed PD-L1 TPS < 50% AND previously completed 4 cycles of standard-of-care platinum based induction chemotherapy with pembrolizumab AND experienced stable disease, partial response, or complete response per investigator's assessment after 4 cycles OR if patients received <4 cycles of a platinum-based induction, was stopped early due to intolerable toxicity Cohort E: Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (non-squamous only) KRASG12C mutation and histologically confirmed PD-L1 TPS < 50% Presence of measurable disease per RECIST v1.1 Exclusion Criteria: All Cohorts: Any prior therapy targeting KRASG12C mutation in any setting Cohorts A & E: Prior systemic therapy for locally advanced or metastatic NSCLC, including chemotherapy, immune checkpoint inhibitor therapy or chemoimmunotherapy (note: prior systemic therapy or chemoradiation given in the adjuvant or neoadjuvant setting are allowed if last dose of prior systemic treatment was >1 year prior to first dose of study treatment) Cohort C: received maintenance therapy (e.g, pembrolizumab and/or pemetrexed following completion of 4-6 cycles of a platinum-based regimen administered in the first-line setting Radiation to the lung > 30 Gy within 6 months prior to first dose of study treatment Active brain metastases
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mirati Therapeutics Study Locator Services
Phone
18448935530
Email
miratistudylocator@careboxhealth.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Mirati Therapeutics Inc.
Official's Role
Study Director
Facility Information:
Facility Name
MemorialCare - Orange Coast Medical Center
City
California City
State/Province
California
ZIP/Postal Code
92708
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amol Rao
Facility Name
MemorialCare - OC Blood and Cancer Center
City
Fountain Valley
State/Province
California
ZIP/Postal Code
92708
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amol Rao
Facility Name
USOR - Rocky Mountain Cancer Centers - Denver - Rose Medical Center Campus
City
Denver
State/Province
Colorado
ZIP/Postal Code
80220
Country
United States
Individual Site Status
Recruiting
Facility Name
The Oncology Institute of Hope and Innovation
City
Lakeland
State/Province
Florida
ZIP/Postal Code
33801
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kamal Sharma
Facility Name
UKCC - Westwood/Richard and Annette Bloch Cancer Care Pavilion
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Zhang
Facility Name
Henry Ford Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shirish Gadgeel, MD
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Name
Hematology Oncology Associates of CNY, PC
City
East Syracuse
State/Province
New York
ZIP/Postal Code
13057
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ajeet Gajra, MD
Facility Name
New York Cancer & Blood Specialists
City
Port Jefferson Station
State/Province
New York
ZIP/Postal Code
11776
Country
United States
Individual Site Status
Recruiting
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nathan Pennell
Facility Name
Texas Oncology Northeast
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Individual Site Status
Recruiting
Facility Name
Texas Oncology - Baylor Charles A. Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Individual Site Status
Recruiting
Facility Name
NEXT Virginia
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting
Facility Name
PeaceHealth St. Joseph Medical Center
City
Bellingham
State/Province
Washington
ZIP/Postal Code
98225
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Drew Murray

12. IPD Sharing Statement

Plan to Share IPD
No

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

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