Adagrasib + Pembrolizumab for Non-Small Cell Lung Cancer

Recruiting at 347 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Mirati Therapeutics Inc.

Must not be taking: QTc prolonging drugs, KRAS inhibitors

Disqualifiers: Autoimmune, Cardiovascular, Bone marrow, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Duration: 12 weeks

630 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a trial to evaluate the efficacy, safety, and tolerability of adagrasib plus pembrolizumab plus platinum-doublet chemotherapy versus placebo plus pembrolizumab plus platinum-doublet chemotherapy in participants with previously untreated, locally advanced or metastatic NSCLC with KRAS G12C mutation

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions that ongoing treatment with medications known to cause prolonged QTc interval must be switched to an alternative before joining the study.

What data supports the effectiveness of the drug combination Adagrasib and Pembrolizumab for treating non-small cell lung cancer?

Research shows that the combination of Adagrasib and Pembrolizumab is effective for patients with a specific type of lung cancer, with response rates of 49% and 57% in two trials. Additionally, Pembrolizumab has been shown to improve outcomes when combined with chemotherapy in lung cancer patients. ^{1 2 3 4 5}

Is pembrolizumab safe for use in humans?

Pembrolizumab has been shown to be generally safe in humans for treating non-small cell lung cancer and other conditions, with studies indicating it has a non-overlapping toxicity profile when used with chemotherapy. ^{3 6 7 8 9}

What makes the Adagrasib + Pembrolizumab treatment unique for non-small cell lung cancer?

The Adagrasib + Pembrolizumab treatment is unique because it targets a specific mutation (KRASG12C) in non-small cell lung cancer, showing promising response rates and lower liver toxicity compared to other similar drug combinations. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with advanced non-squamous non-small cell lung cancer that has a specific mutation (KRAS G12C) and haven't been treated before. Participants should be fit enough for chemotherapy, but those with certain health conditions or previous treatments are excluded.

Inclusion Criteria

I have brain metastases smaller than 20 mm and don't need immediate treatment.

My non-squamous NSCLC has a KRAS G12C mutation.

My cancer can be measured on scans.

Exclusion Criteria

Other protocol-defined Inclusion/Exclusion criteria apply

I haven't had serious heart problems in the last 6 months.

I have been treated with drugs targeting the KRAS G12C mutation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adagrasib plus pembrolizumab plus platinum-doublet chemotherapy or placebo plus pembrolizumab plus platinum-doublet chemotherapy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Adagrasib
• Pembrolizumab
• Platinum-doublet Chemotherapy

Trial Overview The study tests if adding Adagrasib to the standard treatment of Pembrolizumab plus platinum-based chemo (like Cisplatin or Carboplatin) is better than using a placebo with the standard treatment in patients with this type of lung cancer.

Participant Groups

Group I: Adagrasib Experimental Treatment 5 Interventions

Group II: Placebo Placebo Group 5 Interventions

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 pooled analysis of 444 patients with PD-L1-negative advanced/metastatic non-small cell lung cancer (NSCLC), pembrolizumab combined with chemotherapy significantly improved overall survival (hazard ratio 0.63) and progression-free survival (hazard ratio 0.68) compared to chemotherapy alone.

Despite high rates of adverse events (99.2% in the pembrolizumab group), the combination therapy was manageable and resulted in an impressive objective response rate of 87.5% and a 3-year overall survival rate of 100% for patients completing 2 years of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer without tumor PD-L1 expression: A pooled analysis of 3 randomized controlled trials. Borghaei, H., Langer, CJ., Paz-Ares, L., et al.[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]

In a study of 145 patients with PD-L1 strongly positive non-small-cell lung cancer (NSCLC), those with higher PD-L1 expression (≥ 75%) experienced better treatment outcomes with pembrolizumab, showing a higher objective response rate (51% vs. 33%) and longer progression-free survival (13.9 months vs. 5.2 months).

Patients with liver metastasis had significantly poorer responses to pembrolizumab, with an objective response rate of only 20% compared to 47% in those without liver metastasis, indicating that both PD-L1 expression and liver metastasis are important predictors of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC. Takeyasu, Y., Yoshida, T., Shibaki, R., et al.[2021]

Pembrolizumab, when combined with carboplatin and pemetrexed, significantly improves overall and progression-free survival rates in patients with non-small cell lung cancer (NSCLC), demonstrating its efficacy as a treatment option.

This case report highlights a unique instance of immune-mediated sarcoidosis developing in a patient with NSCLC after receiving pembrolizumab, indicating potential immune-related side effects of this therapy that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. Fakhri, G., Akel, R., Salem, Z., et al.[2022]

In a study of 72 treatment-naïve patients with advanced non-small cell lung cancer (NSCLC) and high PD-L1 expression, pembrolizumab showed an objective response rate of 45.8%, with even higher rates of 70.0% in patients with pre-existing interstitial lung disease (ILD).

Patients with ILD had similar overall survival rates compared to those without ILD, suggesting that pembrolizumab can be safely administered to NSCLC patients with ILD without compromising their prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab. Yamaguchi, O., Kaira, K., Shinomiya, S., et al.[2021]

The PePS2 trial demonstrated that pembrolizumab can be safely administered to patients with non-small-cell lung cancer (NSCLC) and a performance status of 2, with a toxicity rate of 28% and no severe treatment-related adverse events, indicating a manageable safety profile.

Efficacy outcomes showed that 38% of first-line and 36% of subsequent-line patients experienced durable clinical benefit, with higher response rates correlating with tumor proportion scores, suggesting that pembrolizumab is effective for this underserved patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial. Middleton, G., Brock, K., Savage, J., et al.[2020]

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]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., et al.[2022]

References

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

Pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer without tumor PD-L1 expression: A pooled analysis of 3 randomized controlled trials. [2021]

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

Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]

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

Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. [2022]

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

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. [2022]

6. Singapore pubmed.ncbi.nlm.nih.gov

Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab. [2021]

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

Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial. [2020]

8. England pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab. [2022]