Pembrolizumab and Trametinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer and KRAS Gene Mutations

NCT03299088 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: 1099442UCDCC#259P30CA093373NCI-2017-01633
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial studies the side effects of pembrolizumab and trametinib in treating patients with non-small cell lung cancer and KRAS gene mutations that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and trametinib may work better in treating patients with non-small cell lung cancer.

Conditions

KRAS Gene Mutation; Metastatic Non-Squamous Non-Small Cell Lung Carcinoma; Recurrent Non-Squamous Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose-limiting Toxicity (DLT) of Pembrolizumab and Trametinib Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.0

  The occurrence of toxicities during the first two cycles (i.e. after completion of the lead in cycle and the first cycle where both pembrolizumab and trametinib are administered) will be considered a DLT, if judged by the Investigator to be possibly, probably or definitely related to study drug administration. Adverse events will be summarized descriptively by type and by severity, with number and relative frequency calculated for all non-zero occurrences.

  Up to 6 weeks

Secondary Outcomes (2)

• Overall Response Rate (ORR)

  Up to 3 years

• Progression-free Survival (PFS)

  Up to 3 years

Study Arms (2)

Arm A (trametinib, pembrolizumab)

EXPERIMENTAL

Patients receive trametinib PO daily. Beginning on day 1 of course 2, patients also receive pembrolizumab IV over 30 minutes. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab; Drug: Trametinib

Arm B (pembrolizumab, trametinib)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Beginning on day 1 of course 2, patients also receive trametinib PO daily. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab; Drug: Trametinib

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Arm A (trametinib, pembrolizumab); Arm B (pembrolizumab, trametinib)

Trametinib DRUG

Given PO

Also known as: GSK1120212, JTP-74057, MEK Inhibitor GSK1120212, Mekinist

Arm A (trametinib, pembrolizumab); Arm B (pembrolizumab, trametinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage IV or metastatic/recurrent non-small cell lung cancer; for expansion cohorts, patient's tumor must also harbor a KRAS mutation detected in a CLIA certified laboratory
• Have histologically or cytologically confirmed non-small cell lung cancer
• Have stage IV, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) with progressive disease after platinum containing chemotherapy (EGFR mutant, ALK, or ROS-1 rearranged NSCLC must have progressed on prior approved tyrosine kinase inhibitor \[TKI\]'s)
• For phase I dose expansion cohorts the patient's tumor must harbor a KRAS mutation detected by a CLIA certified laboratory
• Be willing and able to provide written informed consent/assent for the trial
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; in the opinion of the investigator, the patient must have tumor accessible by CT or ultrasound guided core biopsy; subjects for whom newly-obtained samples cannot be provided may submit an archived specimen provided it was obtained after last systemic treatment, within 6 months of signing consent and that tissue is available for either 2 cell blocks or 20 uncut slides (core or excisional biopsy required, fine needle aspirate is not acceptable)
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
• Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• Absolute neutrophil count \>= 1.5 x 10\^9/L
• Hemoglobin \>= 9 g/dL
• Platelets \>= 100 x 10\^9/L
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.5 x upper limit of normal (ULN)
• Albumin \>= 2.5 g/dL
• Total bilirubin =\< 1.5 x ULN

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 3 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment; inhaled or topical steroids are allowed
• Has a known history of active tuberculosis (TB \[Bacillus Tuberculosis\])
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 3 weeks earlier
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent; note: subjects with =\< grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study; note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of, or any evidence of active, non-infectious pneumonitis; history of radiation pneumonitis is allowed provided that it is not active and no corticosteroids were required for pneumonitis management
• Evidence of interstitial lung disease
• Has an active infection requiring systemic therapy
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib, or excipients or to dimethyl sulfoxide (DMSO)
• History of retinal vein occlusion (RVO)
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Sponsors & Collaborators

• Jonathan Riess: lead
• Merck Sharp & Dohme LLC: collaborator
• Novartis: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; trametinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Leslie Garcia
• Organization: U of California Davis

lesgarcia@ucdavis.edu

916-734-0156

Study Officials

• Jonathan Riess

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 27, 2017
• First Posted: October 2, 2017
• Study Start: June 26, 2018
• Primary Completion: January 28, 2021
• Study Completion: June 25, 2024
• Last Updated: May 21, 2025
• Results First Posted: May 21, 2025

Record last verified: 2025-05

Locations

US (1)