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

Purpose

Study CA239-0010 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

Conditions

  • Advanced NSCLC
  • Metastatic Lung Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

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

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort A: PD-L1 TPS≥ 1% (Closed) 		Adagrasib 400 mg BID for 2 cycles followed by adagrasib 400 mg BID + pembrolizumab 200 mg every 3 weeks (Q3W) up to 35 cycles
  • Drug: Adagrasib oral dose of 400 mg twice daily tablets
    oral dose of 400 mg twice daily tablets
Experimental
Cohort C 		Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles
  • Drug: Adagrasib oral dose of 400 mg twice daily tablets
    oral dose of 400 mg twice daily tablets
  • Combination Product: Pembrolizumab
    IV infusion once every 3 weeks
  • Combination Product: Chemotherapy: Pemetrexed
    IV infusion once every 3 weeks
  • Combination Product: Cisplatin/Carboplatin
    IV infusion once every 3 weeks
Experimental
Cohort E 		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)
  • Drug: Adagrasib oral dose of 400 mg twice daily tablets
    oral dose of 400 mg twice daily tablets
  • Combination Product: Pembrolizumab
    IV infusion once every 3 weeks
  • Combination Product: Chemotherapy: Pemetrexed
    IV infusion once every 3 weeks
  • Combination Product: Cisplatin/Carboplatin
    IV infusion once every 3 weeks

Recruiting Locations

University of Kansas Cancer Center - Westwood/Richard and Annette Bloch Cancer Care Pavilion
Westwood, Kansas 66205
Contact:
Jun Zhang, Site 017-820
415-244-4731

More Details

Status
Recruiting
Sponsor
Mirati Therapeutics Inc.

Study Contact

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
855-907-3286
Clinical.Trials@bms.com