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

NCT03225664 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 2017-0226NCI-2018-01107R01CA155196
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Metastatic Lung Non-Small Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Stage III Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Unresectable Lung Non-Small Cell Carcinoma; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Overall objective response rate evaluated according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1 and immune related [ir]RECIST)

  Each patient will have the KRAS mutation and PD-L1 status determined prior to treatment in order for stratified randomization. A futility monitoring will be carried out continuously to each stratum within each treatment arm after the primary endpoints of 6 patients have been observed in the corresponding marker groups.

  At 6 months

Study Arms (1)

Treatment (trametinib, pembrolizumab)

EXPERIMENTAL

Patients receive trametinib PO 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 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.

Biological: Pembrolizumab; Other: Pharmacokinetic Study; Drug: Trametinib

Interventions

Pembrolizumab BIOLOGICAL

Given IV

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

Treatment (trametinib, pembrolizumab)

Pharmacokinetic Study OTHER

Correlative studies

Also known as: PHARMACOKINETIC, PK Study

Treatment (trametinib, pembrolizumab)

Trametinib DRUG

Given PO

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

Treatment (trametinib, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• 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
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN except for subjects with liver metastases (mets) for whom ALT and AST should be =\< 5 x ULN
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated PTT (aPTT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulant
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female and male subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

You may not qualify if:

• 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
• 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 evidence of interstitial lung disease or active, non-infectious pneumonitis, or has history of pneumonitis that required systemic corticosteroids for recovery
• Has an active infection requiring systemic therapy
• Has symptomatic ascites or pleural effusion. A subject who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible
• 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 study, or in the opinion of the investigator, is not in the best interest of the subject to participate

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Yale University

New Haven, Connecticut, 06520, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

pembrolizumab; Pharmacogenomic Variants; trametinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Polymorphism, Genetic; Genetic Variation; Genetic Phenomena

Study Officials

• Ferdinandos Skoulidis, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2017
• First Posted: July 21, 2017
• Study Start: February 3, 2018
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 16, 2026

Record last verified: 2026-01

Locations

US (2)