Adagrasib + Pembrolizumab for Lung Cancer

Recruiting at 854 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Mirati Therapeutics Inc.

Must not be taking: Chemotherapy, Immune checkpoint inhibitors

Disqualifiers: Active brain metastases, Seizures, 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

Compensation: Varies

Number of Visits: Unknown

806 Participants Needed

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.

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. ^{1 2 3 4 5}

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. ^{1 2 3 6 7}

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. ^{1 2 3 5 6}

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 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.

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.

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
• MRTX849
• Pembrolizumab
• Phase 3 comparator arm

Trial Overview The 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

Group I: Phase 3 Cohort 3 Investigational Arm Experimental Treatment 1 Intervention

Adagrasib BID in combination with pembrolizumab

Group II: Phase 2 Cohort 2: PD-L1 TPS ≥1% Experimental Treatment 1 Intervention

Cohort 2: Adagrasib BID in combination with pembrolizumab

Group III: Phase 2 Cohort 1b: PD-L1 TPS <1% Experimental Treatment 1 Intervention

Cohort 1b: Adagrasib BID monotherapy

Group IV: Phase 2 Cohort 1a: PD-L1 TPS <1% Experimental Treatment 1 Intervention

Cohort 1a: Adagrasib twice daily (BID) in combination with pembrolizumab

Group V: Phase 3 Cohort 4 Comparator Arm Active Control 1 Intervention

Pembrolizumab

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

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

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

Another KRAS Inhibitor Holds Its Own. [2021]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]