Trial results for the Phase 1 study (NCT03299088) investigating pembrolizumab and trametinib in patients with Stage IV non-small cell lung cancer (NSCLC) with KRAS gene mutations were posted on ClinicalTrials.gov on 2025-05-21. The study primarily evaluated the incidence of dose-limiting toxicities (DLTs), reporting 0 or 1 DLT across most dose escalation arms.
Background
The trial investigated the combination of pembrolizumab (Keytruda) and trametinib in treating patients with Stage IV non-small cell lung cancer (NSCLC) and KRAS gene mutations. Pembrolizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Trametinib may stop the growth of tumor cells by blocking enzymes needed for cell growth. The study aimed to explore the potential for this combination to work better in treating non-small cell lung cancer.
Trial design
The Phase 1 study (NCT03299088) was a completed trial that enrolled 15 participants. The study investigated pembrolizumab and trametinib in patients diagnosed with Stage IV Non-Small Cell Lung Cancer AJCC v7, including those with KRAS Gene Mutation, Metastatic Non-Squamous Non-Small Cell Lung Carcinoma, or Recurrent Non-Squamous Non-Small Cell Lung Carcinoma. The primary outcome measured was the incidence of dose-limiting toxicity (DLT) of pembrolizumab and trametinib per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.0 across different dose escalation arms.
Key results
The trial results focused on the incidence of dose-limiting toxicities (DLTs) and exploratory efficacy outcomes such as Overall Response Rate (ORR) and Progression-free Survival (PFS).
- For "Incidence of Dose-limiting Toxicity (DLT) of Pembrolizumab and Trametinib Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.0":
- Escalation Arm A Dose Level 1 reported 0 DLT.
- Escalation Arm A Dose Level 2 reported 1 DLT.
- Escalation Arm B Dose Level 1 reported 0 DLT.
- Escalation Arm B Dose Level 2 reported 0 DLT.
- For "Overall Response Rate (ORR)":
- Escalation Arm A Dose Level 1 showed an ORR of 6 percentage of participants.
- Escalation Arm A Dose Level 2 showed an ORR of 0 percentage of participants.
- Escalation Arm B Dose Level 1 showed an ORR of 0 percentage of participants.
- Escalation Arm B Dose Level 2 showed an ORR of 6 percentage of participants.
- For "Progression-free Survival (PFS)":
- Escalation Arm A Dose Level 1 had a median PFS of 4.79 months.
- Escalation Arm A Dose Level 2 had a median PFS of 0 months.
- Escalation Arm B Dose Level 1 had a median PFS of 2.08 months.
- Escalation Arm B Dose Level 2 had a median PFS of 0 months.
What this means
The results from this Phase 1 study indicate that the combination of pembrolizumab and trametinib demonstrated a generally manageable safety profile in patients with Stage IV NSCLC and KRAS gene mutations, with a low incidence of dose-limiting toxicities observed across most dose escalation arms. While the overall response rates and progression-free survival were variable and low in some arms, these are exploratory endpoints for a Phase 1 trial primarily designed to assess safety and determine optimal dosing for further study. The findings support continued investigation into this combination therapy, potentially in larger trials to further evaluate efficacy.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03299088, titled "Pembrolizumab and Trametinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer and KRAS Gene Mutations," were posted on 2025-05-21 on clinicaltrials.gov.