Adagrasib Combo Therapy for Lung Cancer

(202200050434 Trial)

Recruiting at 160 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mirati Therapeutics Inc.

Must be taking: Platinum-based chemotherapy

Must not be taking: KRASG12C inhibitors

Disqualifiers: Active brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 31 cycles

90 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have had prior therapy targeting the KRASG12C mutation or certain treatments for advanced NSCLC, you may not be eligible to participate.

What makes the drug Adagrasib unique for lung cancer treatment?

Adagrasib is unique because it specifically targets the KRAS G12C mutation found in some lung cancers, locking the mutant protein in an inactive state to stop cancer growth. It is taken orally and has shown promising response rates with lower liver toxicity compared to other similar treatments. ^{1 2 3 4 5}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that has a specific mutation called KRAS G12C. Participants must have measurable disease and varying levels of PD-L1 expression, depending on the cohort they fall into. They should not have received certain prior treatments for NSCLC or have active brain metastases.

Inclusion Criteria

I have NSCLC with a KRASG12C mutation, PD-L1 < 50%, and responded to or couldn't tolerate initial chemotherapy.

My NSCLC is untreated, can't be surgically removed, has a KRASG12C mutation, and PD-L1 TPS is below 50%.

My NSCLC is untreated, can't be surgically removed, has a KRASG12C mutation, and PD-L1 TPS is 1% or more.

Exclusion Criteria

I received maintenance therapy with pembrolizumab or pemetrexed after initial platinum-based treatment.

I have not had lung radiation over 30 Gy in the last 6 months.

I've had treatment for advanced lung cancer but not within the last year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adagrasib in combination with pembrolizumab and chemotherapy

Up to 31 cycles

Every 3 weeks

Safety Lead In (SLI)

Participants are monitored for dose-limiting toxicities during the initial treatment cycle

1 cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 months

Treatment Details

Interventions

• Adagrasib
• Pembrolizumab

Trial Overview The study tests adagrasib combined with pembrolizumab and chemotherapy (pemetrexed, cisplatin/carboplatin) in patients with NSCLC who haven't been treated before or those who've had stable disease after initial chemo. It's an open-label Phase 2 trial to see how well this combination works.

Participant Groups

Group I: Cohort E Experimental Treatment 4 Interventions

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)

Group II: Cohort C Experimental Treatment 4 Interventions

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

Group III: Cohort A: PD-L1 TPS≥ 1% (Closed) Experimental Treatment 1 Intervention

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 is already approved in United States, European Union for the following indications:

Approved in United States as Krazati for:

• KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)
• KRAS G12C-mutated locally advanced or metastatic colorectal cancer

Approved in European Union as Krazati for:

• KRAS G12C mutation non-small cell lung cancer

Who Is Running the Clinical Trial?

Mirati Therapeutics Inc.

Lead Sponsor

Trials

73

Recruited

8,900+

Dr. Charles M. Baum

Mirati Therapeutics Inc.

Chief Executive Officer since 2023

MD, PhD

Dr. Joseph Leveque

Mirati Therapeutics Inc.

Chief Medical Officer since 2021

MD

Findings from Research

Adagrasib (KRAZATI™) is an effective oral treatment specifically targeting the KRAS G12C mutation in solid tumors, particularly non-small cell lung cancer (NSCLC), by locking the mutant protein in an inactive state, which prevents cancer cell signaling.

In December 2022, adagrasib received accelerated approval in the USA for adults with KRAS G12C-mutated NSCLC who have undergone prior systemic therapy, based on its promising response rates, although further confirmatory trials are needed to establish its clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adagrasib: First Approval. Dhillon, S.[2023]

In a phase I/IB study involving 25 patients with advanced KRASG12C-mutant solid tumors, adagrasib (600 mg twice daily) demonstrated significant antitumor activity, with 53.3% of patients with non-small-cell lung cancer achieving a confirmed partial response after a median follow-up of 19.6 months.

Adagrasib was well tolerated, with the most common side effects being nausea (80%), diarrhea (70%), and fatigue (45%), indicating a manageable safety profile for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1). Ou, SI., Jänne, PA., Leal, TA., et al.[2023]

The KRYSTAL-1 study found that adagrasib (MRTX849), a KRASG12c inhibitor, is generally well tolerated by patients with non-small cell lung cancer, indicating a favorable safety profile.

Adagrasib demonstrated significant efficacy in treating non-small cell lung cancer with the KRASG12c mutation, and it also showed some activity in colorectal cancer and other solid tumors, although to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Another KRAS Inhibitor Holds Its Own. [2021]

Adagrasib combined with pembrolizumab shows promising efficacy for patients with newly diagnosed non-small cell lung cancer with a KRASG12C mutation, achieving overall response rates of 49% and 57% in two separate trials.

This drug combination demonstrated a favorable safety profile, exhibiting lower liver toxicity compared to other combinations of checkpoint inhibitors and targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]

Adagrasib, a newly approved KRASG12C-targeted therapy, shows a clinical efficacy with an objective response rate of 42.9% and a median duration of response of 8.5 months in patients with advanced KRASG12C-mutated non-small-cell lung cancer.

While adagrasib is effective, it is associated with a high incidence of treatment-related adverse events, primarily gastrointestinal, affecting 97.4% of patients, with 44.8% experiencing severe (grade 3+) side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adagrasib: a novel inhibitor for KRASG12C-mutated non-small-cell lung cancer. Guo, MZ., Marrone, KA., Spira, A., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Adagrasib: First Approval. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1). [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Another KRAS Inhibitor Holds Its Own. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Adagrasib: a novel inhibitor for KRASG12C-mutated non-small-cell lung cancer. [2023]