Loading clinical trials...

Trametinib and Pembrolizumab in Treating Patients With Recurrent Non-small Cell Lung Cancer That Is Metastatic, Unresectable, or Locally Advanced | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE1/PHASE2

Trametinib and Pembrolizumab in Treating Patients With Recurrent Non-small Cell Lung Cancer That Is Metastatic, Unresectable, or Locally Advanced

A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer - (IM-BATTLE-2 Program)

NCT03225664•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

This phase Ib/II trial studies the side effects and best dose of trametinib when given together with pembrolizumab and to see how well they work in treating patients with non-small cell lung cancer that has come back and spread to other places in the body, cannot be removed by surgery, or spread to nearby tissues or lymph nodes. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving trametinib and pembrolizumab may work better in treating patients with non-small cell lung cancer.

Detailed Description

PRIMARY OBJECTIVES: I. To evaluate the toxicity profile of trametinib, a MEK inhibitor, in combination with pembrolizumab, an anti PD-1 monoclonal antibody, as treatment for refractory to chemotherapy KRAS mutation positive (mut+) and KRAS wild-type patients with advanced non-small cell lung cancer (NSCLC) and establish a recommended dose for the combination for the phase II portion of the study. (Part 1) II. To determine the 6-month overall response rate (ORR) for the combination of trametinib + pembrolizumab in subjects with NSCLC who received prior cytotoxic chemotherapy and anti-PD1 or anti-PD-L1 therapy. (Part 2) SECONDARY OBJECTIVES: I. To evaluate overall response rates (ORRs) using modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1 and immune related \[ir\]RECIST) and duration of response (DOR), median progression free survival (PFS) and overall survival (OS) in KRAS mut+, KRAS wild-type, PD-L1+ and PD-L1 negative cohorts of patients. II. To evaluate ORRs by immune-related RECIST (irRECIST). III. To assess the safety and tolerability of pembrolizumab in combination with trametinib at the recommended dose to be used in future studies. IV. To characterize the pharmacokinetics of trametinib and pembrolizumab when administered in combination. V. To identify prognostic and predictive markers for the two treatment regimens by analyzing pre- and on-treatment tumor biopsies. EXPLORATORY OBJECTIVES: I. Evaluate exploratory genomic and gene expression biomarkers and their relationships in tumors in response to study treatment. II. Analyze circulating soluble factors including cytokines, chemokines, and antibodies against tumor and self antigens in response to clinical outcomes. III. Assess the activation state, quantity, and phenotype of T cells, B cells, and natural killer cells and the presence of immune regulatory cells (myeloid-derived suppressor cells) (MDSC) in response to treatment. IV. Examine changes in the localization and numbers of tumor infiltrating lymphocytes (TILs) expressing key markers (PD-1, CD8, CD4, CD45RO, granzyme, CD68, Foxp3) by immunohistochemistry in response to treatment. V. Perform immune monitoring studies in tissue and blood and correlate with genomic profiling and outcomes including toxicities. VI. Evaluate KRAS-mutation specific T cell response in patients before and after monotherapy with PEMBROLIZUMAB and the combination of PEMBROLIZUMAB and trametinib. VII. Evaluate immunophenotypes within the context of subsets of KRAS co-mutations (KRAS/p53, KRAS/LKB1, KRAS/CDKN2A/B inactivation). VIII. Collect and store archival diagnostic tumor samples, matched pre- and post-treatment tumor biopsy samples and deoxyribonucleic acid (DNA) (from tumor and blood) for future exploratory research into genes/genetic variation and factors that may influence resistance and/or sensitivity, and/or response to trametinib and/or PEMBROLIZUMAB. IX. Explore the relationship between pharmacokinetic (PK) plasma trametinib levels, trametinib exposure, safety and clinical outcome measures. X. Isolate peripheral blood mononuclear cells (PBMCs) from whole blood to enable flow cytometric analysis of additional markers and perform functional testing for antigen specificity and responsiveness, and T cell receptor (TCR) diversity. XI. Perform flow cytometric analyses in tumor tissue. XII. Analysis of the host microbiome from stool. XIII. Analysis of micro ribonucleic acid (miRNA) platelets and analysis in response to study treatment. OUTLINE: This is a phase Ib, dose-escalation study of trametinib followed by a phase II study. Patients receive trametinib orally (PO) once daily (QD) 14 days prior to cycle 1 and days 1-10 of each course (10 days on, 11 days off). Beginning in cycle 2, participants also receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and every 3 months for up to 3 years.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Histologically or cytologically confirmed diagnosis of metastatic or unresectable, locally advanced, recurrent NSCLC that has been previously treated (subjects who have failed adjuvant or locally advanced therapy within 6 months are also eligible to participate in the study)
•The subject has biopsy accessible tumor and is willing to undergo biopsy prior to planned protocol treatment
•Confirmation of the presence or absence of EGFR mutations and ALK gene fusions prior to study enrollment in all subjects except for patients with histologies other than adenocarcinoma and NSCLC, not otherwise specified (NOS), as the frequency of these alterations is exceedingly rare in this histology. Subjects with known EGFR sensitizing mutational status or ALK fusion must have been treated and progressed on EGFR TKIs or ALK-directed therapy, or with tumors harboring EGFR T790M mutation to have received and progressed on therapy directed at the T790M mutation (e.g. osimertinib). Subjects with known ROS1 translocation must have been treated and progressed on ROS1-directed therapy
•Measurable disease according to RECIST 1.1 and irRECIST. At least one lesion of at least 1.0 cm in the long-axis diameter for a non-lymph node or at least 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 and irRECIST using either computed tomography (CT) or magnetic resonance imaging (MRI). If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of at least 1.5 cm
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
•Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L or at least 1500/mm\^3 or at least 1.5 x 10\^9/L
•Platelet count at least 100,000/mm\^3 or at least 100 x 10\^9/L
•Hemoglobin (Hb) at least 9 g/dL (or 5.69 mmol/L) at baseline (blood transfusions, hematopoietic growth factors and hematinics are not allowed during the 7 days prior to screening to correct Hb values less than 9 g/dL)
•Serum creatinine =\< 1.5 x upper limit of normal (ULN) or \>= 60 mL/minute for subjects with creatinine levels \> 1.5 x the institutional ULN
•Serum total bilirubin =\< 1.5 x ULN or direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN
+12 more criteria

Exclusion Criteria

•Subjects participating in or who have participated in a study of an investigational agent or is using an investigational device within 4 weeks of the first dose of study treatment or have received any anti-cancer therapy, platinum-based chemotherapy, targeted, biological (including humanized antibodies), investigational, immunotherapy, or hormonal agent, within 4 weeks of the first dose of study 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
•Has had prior monoclonal antibody therapy within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events (AEs) due to agents administered more than 4 weeks earlier
•Has received previous treatment with an immunomodulatory therapy (eg, anti PD 1/PD L1 or CTLA-4 agent) and was discontinued from that therapy due to a grade 3 or higher immune-related adverse event (irAE)
•Had prior chemotherapy, targeted small molecule therapy within 4 weeks, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from AEs due to a previously administered agent
•* Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
•* Note: if a subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
•* Note: patients who have received \> 30 Gy to the thorax must have completed this radiation 6 months prior to enrollment in the study
•Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell and squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
•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 4 weeks prior to the first dose of study 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 study treatment
+13 more criteria

Locations (2)

Yale University

New Haven, Connecticut, United States

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

February 3, 2018

Primary Completion Date

December 31, 2027

Completion Date

December 31, 2027

Last Updated

January 16, 2026

Enrollment

ACTUAL participants

Conditions

Metastatic Lung Non-Small Cell CarcinomaRecurrent Lung Non-Small Cell CarcinomaStage III Lung Cancer AJCC v8Stage IIIA Lung Cancer AJCC v8Stage IIIB Lung Cancer AJCC v8Stage IIIC Lung Cancer AJCC v8Stage IV Lung Cancer AJCC v8Stage IVA Lung Cancer AJCC v8Stage IVB Lung Cancer AJCC v8Unresectable Lung Non-Small Cell Carcinoma

Interventions

Pembrolizumab

BIOLOGICAL

Pharmacokinetic Study

OTHER

Trametinib

DRUG

Testing the Addition of an Anti-Cancer Drug, TRC102, to the Usual Chemotherapy Treatment (Pemetrexed, Cisplatin or Carboplatin) During Radiation Therapy for Stage III Non-Squamous Non-Small Cell Lung Cancer

NCT05198830

Lung AdenocarcinomaLung Large Cell Carcinoma+2 more

View study

RECRUITINGPHASE2

Testing Osimertinib as a Treatment for Lung Cancers With an EGFR Exon 20 Change

NCT03191149

Advanced Lung Non-Small Cell CarcinomaRecurrent Lung Non-Small Cell Carcinoma+2 more

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 16, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Trametinib and Pembrolizumab in Treating Patients With Recurrent Non-small Cell Lung Cancer That Is Metastatic, Unresectable, or Locally Advanced

Inclusion Criteria

Exclusion Criteria

Testing the Addition of an Anti-Cancer Drug, TRC102, to the Usual Chemotherapy Treatment (Pemetrexed, Cisplatin or Carboplatin) During Radiation Therapy for Stage III Non-Squamous Non-Small Cell Lung Cancer

Testing Osimertinib as a Treatment for Lung Cancers With an EGFR Exon 20 Change

Immune Checkpoint Inhibitor Response in Solid Tumors Using a Live Tumor Diagnostic Platform

A Tool for Improving the Shared Decision-making Process in Patients With Non-small Cell Lung Cancer

Adaptive Radiation Planning for the Reduction of Radiation-Induced Toxicity in Patients With Stage II-IV Non-small Cell Lung Cancer

Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has a MET Exon 14 Skipping Gene Change (An Expanded Lung-MAP Treatment Trial)