~360 spots leftby Oct 2028

Adagrasib + Pembrolizumab for Lung Cancer

Recruiting at851 trial locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Mirati Therapeutics Inc.
Must not be taking: Chemotherapy, Immune checkpoint inhibitors
Disqualifiers: Active brain metastases, Seizures, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests two drugs, MRTX849 and pembrolizumab, in patients with advanced lung cancer who have a specific genetic mutation. MRTX849 targets the mutation to stop cancer growth, while pembrolizumab boosts the immune system to fight the cancer. The study aims to see how well these treatments work alone and together.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who have had prior systemic treatment for advanced NSCLC. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Adagrasib and Pembrolizumab for lung cancer?

Early trials show that the combination of Adagrasib and Pembrolizumab is effective for patients with a specific type of lung cancer (KRASG12C mutation), with response rates of 49% and 57% in two different studies. Additionally, this combination has lower liver toxicity compared to other similar treatments.12345

Is the combination of Adagrasib and Pembrolizumab safe for humans?

Early trials suggest that the combination of Adagrasib and Pembrolizumab is generally safe for patients with non-small cell lung cancer, showing lower levels of liver toxicity compared to other similar treatments. Pembrolizumab alone has been associated with some side effects like fatigue, cough, and nausea, and can cause immune-related issues such as inflammation in the lungs or liver.12356

How is the drug combination of Adagrasib and Pembrolizumab unique for lung cancer treatment?

The combination of Adagrasib and Pembrolizumab is unique because it targets a specific mutation (KRASG12C) in non-small cell lung cancer and has shown promising response rates with lower liver toxicity compared to other similar treatments.12347

Research Team

BS

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 no prior treatments for metastatic NSCLC. Those with certain brain metastases can join if they don't require immediate treatment.

Inclusion Criteria

My brain scans show no signs of cancer, or I have brain cancer that doesn't need immediate treatment.
My NSCLC is inoperable or has spread, with a KRAS G12C mutation.
You have a measurable disease according to RECIST criteria.
See 1 more

Exclusion Criteria

I have had treatments like chemotherapy or immunotherapy for advanced lung cancer.
I don't have large untreated brain lesions, brainstem lesions, high steroid use for brain symptoms, frequent seizures, or worsening neurological symptoms due to brain lesions.
I have active cancer spread to my brain.
See 1 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 2 Treatment

Participants receive MRTX849 monotherapy or in combination with pembrolizumab for advanced NSCLC with KRAS G12C mutation

22 months

Phase 3 Treatment

Participants receive adagrasib in combination with pembrolizumab versus pembrolizumab alone for advanced NSCLC with KRAS G12C mutation

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

  • Adagrasib (Small Molecule Drug)
  • MRTX849 (Small Molecule Drug)
  • Pembrolizumab (Checkpoint Inhibitor)
  • Phase 3 comparator arm (Chemotherapy)
Trial OverviewThe study tests MRTX849 alone and combined with Pembrolizumab in Phase 2, while Phase 3 compares Adagrasib plus Pembrolizumab against only Pembrolizumab in patients whose tumors show high levels of a protein called PD-L1.
Participant Groups
5Treatment groups
Experimental Treatment
Active Control
Group I: Phase 3 Cohort 3 Investigational ArmExperimental Treatment1 Intervention
Adagrasib BID in combination with pembrolizumab
Group II: Phase 2 Cohort 2: PD-L1 TPS ≥1%Experimental Treatment1 Intervention
Cohort 2: Adagrasib BID in combination with pembrolizumab
Group III: Phase 2 Cohort 1b: PD-L1 TPS <1%Experimental Treatment1 Intervention
Cohort 1b: Adagrasib BID monotherapy
Group IV: Phase 2 Cohort 1a: PD-L1 TPS <1%Experimental Treatment1 Intervention
Cohort 1a: Adagrasib twice daily (BID) in combination with pembrolizumab
Group V: Phase 3 Cohort 4 Comparator ArmActive Control1 Intervention
Pembrolizumab

Find a Clinic Near You

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

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.
The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience.Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]
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.
Frontline Promise for Adagrasib-Pembrolizumab Combination.[2023]
Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.
Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions.Karim, S., Leighl, N.[2017]

References

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]
Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]
Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]
Another KRAS Inhibitor Holds Its Own. [2021]
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]
Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]