Adagrasib + Pembrolizumab for Lung Cancer
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Mirati Therapeutics Inc.
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.
What safety data exists for the Adagrasib and Pembrolizumab treatment for lung cancer?The combination of Adagrasib and Pembrolizumab has shown early evidence of being a safe and effective treatment for non-small cell lung cancer with a KRASG12C mutation, with lower levels of liver toxicity compared to other combinations. Pembrolizumab, as a PD-1 inhibitor, has been used in various cancers and is generally well-tolerated, though it can cause immune-mediated adverse reactions such as pneumonitis, colitis, and hepatitis. Adagrasib has been reported to be well-tolerated in the KRYSTAL-1 study for non-small cell lung cancer.23457
Is the drug combination of Adagrasib and Pembrolizumab promising for lung cancer?Yes, the combination of Adagrasib and Pembrolizumab is promising for lung cancer. It has shown to be safe and effective, with response rates of 49% and 57% in trials, and it causes less liver toxicity compared to other treatments.12567
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. However, you cannot have had prior systemic treatment for advanced NSCLC, including chemotherapy or therapies targeting KRAS G12C mutation.
What data supports the idea that Adagrasib + Pembrolizumab for Lung Cancer is an effective treatment?The available research shows that the combination of Adagrasib and Pembrolizumab is effective for treating non-small cell lung cancer with a specific mutation called KRASG12C. In one trial, nearly half of the patients (49%) responded positively to the treatment, and in another trial, the response rate was even higher at 57%. Additionally, this combination has been found to cause less liver damage compared to other similar treatments, making it a safer option for patients.24567
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 NSCLC is inoperable or has spread, with a KRAS G12C mutation.
My NSCLC is inoperable or has spread, with a KRAS G12C mutation and high PD-L1 levels.
Exclusion Criteria
I have had treatments like chemotherapy or immunotherapy for advanced lung cancer.
I have active cancer spread to my brain.
I have not received lung radiation over 30 Gy in the last 6 months.
Treatment Details
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.
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
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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Local Institution - 007-556-AGoodyear, AZ
Local Institution - 007-568-ASafford, AZ
Local Institution - 007-568-BSafford, AZ
Local Institution - 007-568-CSafford, AZ
More Trial Locations
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Who is running the clinical trial?
Mirati Therapeutics Inc.Lead Sponsor
References
Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Another KRAS Inhibitor Holds Its Own. [2021]According to the KRYSTAL-1 study, the KRASG12c inhibitor adagrasib, also known as MRTX849, is largely well tolerated and shows considerable efficacy in patients with non-small cell lung cancer harboring this mutation. The drug is also active, albeit more modestly, in colorectal cancer and several other solid tumor types.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]Pembrolizumab is a programmed death receptor-1 masking antibody approved for metastatic non-small cell lung cancer. This Phase 2 study (NCT02818920) of neoadjuvant pembrolizumab in non-small cell lung cancer had a primary end point of safety and secondary end points of efficacy and correlative science.
Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]Two trials offer early evidence that adagrasib plus pembrolizumab is a safe and effective regimen for patients with newly diagnosed non-small cell lung cancer harboring a KRASG12C mutation. The overall response rate in one trial was 49%, and in the other it was 57%. The drug combination showed lower levels of liver toxicity than other combinations of checkpoint inhibitors and targeted therapies.