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

Phase 1

Active, not recruiting

• Conditions: Metastatic Lung Non-Small Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Stage III Lung Cancer AJCC v8; 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; Stage IVB Lung Cancer AJCC v8; Unresectable Lung Non-Small Cell Carcinoma

• Registration Number: NCT03225664
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-7-14
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Active, not recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria:<br><br> - Histologically or cytologically confirmed diagnosis of metastatic or unresectable,<br> locally advanced, recurrent NSCLC that has been previously treated (subjects who<br> have failed adjuvant or locally advanced therapy within 6 months are also eligible<br> to participate in the study)<br><br> - The subject has biopsy accessible tumor and is willing to undergo biopsy prior to<br> planned protocol treatment<br><br> - Confirmation of the presence or absence of EGFR mutations and ALK gene fusions prior<br> to study enrollment in all subjects except for patients with histologies other than<br> adenocarcinoma and NSCLC, not otherwise specified (NOS), as the frequency of these<br> alterations is exceedingly rare in this histology. Subjects with known EGFR<br> sensitizing mutational status or ALK fusion must have been treated and progressed on<br> EGFR TKIs or ALK-directed therapy, or with tumors harboring EGFR T790M mutation to<br> have received and progressed on therapy directed at the T790M mutation (e.g.<br> osimertinib). Subjects with known ROS1 translocation must have been treated and<br> progressed on ROS1-directed therapy<br><br> - Measurable disease according to RECIST 1.1 and irRECIST. At least one lesion of at<br> least 1.0 cm in the long-axis diameter for a non-lymph node or at least 1.5 cm in<br> the short-axis diameter for a lymph node which is serially measurable according to<br> RECIST 1.1 and irRECIST using either computed tomography (CT) or magnetic resonance<br> imaging (MRI). If there is only one target lesion and it is a non-lymph node, it<br> should have a longest diameter of at least 1.5 cm<br><br> - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1<br><br> - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L or at least 1500/mm^3 or at least<br> 1.5 x 10^9/L<br><br> - Platelet count at least 100,000/mm^3 or at least 100 x 10^9/L<br><br> - Hemoglobin (Hb) at least 9 g/dL (or 5.69 mmol/L) at baseline (blood transfusions,<br> hematopoietic growth factors and hematinics are not allowed during the 7 days prior<br> to screening to correct Hb values less than 9 g/dL)<br><br> - Serum creatinine =< 1.5 x upper limit of normal (ULN) or >= 60 mL/minute for<br> subjects with creatinine levels > 1.5 x the institutional ULN<br><br> - Serum total bilirubin =< 1.5 x ULN or direct bilirubin =< ULN for subjects with<br> total bilirubin levels > 1.5 x ULN<br><br> - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN<br> except for subjects with liver metastases (mets) for whom ALT and AST should be =< 5<br> x ULN<br><br> - International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless<br> subject is receiving anticoagulant therapy as long as PT or partial thromboplastin<br> time (PTT) is within therapeutic range of intended use of anticoagulants<br><br> - Activated PTT (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy<br> as long as PT or PTT is within therapeutic range of intended use of anticoagulant<br><br> - Female subject of childbearing potential should have a negative urine or serum<br> pregnancy within 72 hours prior to receiving the first dose of study medication. If<br> the urine test is positive or cannot be confirmed as negative, a serum pregnancy<br> test will be required. Female and male subjects of childbearing potential must be<br> willing to use an adequate method of contraception for the course of the study<br> through 120 days after the last dose of study medication. Note: abstinence is<br> acceptable if this is the usual lifestyle and preferred contraception for the<br> subject<br><br> - Voluntary agreement to provide written informed consent and the willingness and<br> ability to comply with all aspects of the protocol<br><br> - Patients must be able to swallow and retain oral medication and must not have any<br> clinically significant gastrointestinal abnormalities that may alter absorption such<br> as malabsorption syndrome or major resection of the stomach or bowels<br><br> - Prior MEK inhibitor therapy is allowed<br><br> - Prior anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic<br> T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any<br> other antibody or drug specifically targeting T-cell co-stimulation or checkpoint<br> pathways) is required for phase 2 part of the study. Subjects must be resistant (at<br> least stable disease at 12 weeks of treatment with anti-PD1, anti-PD-L1 therapy)<br> (cohort A) or refractory (progression within 12 weeks of starting anti-PD1 therapy)<br> (cohort B) to an Food and Drug Administration (FDA) approved anti PD 1/PD L1<br> monoclonal antibody (mAb) as either monotherapy or in combination with other<br> approved checkpoint inhibitors or other therapies according to their label, defined<br> as (subjects must meet all of the following criteria):<br><br> - Have received at least 2 doses of anti PD 1/PD L1 mAb<br><br> - Progressive disease after anti PD 1/PD L1 mAb defined according to RECIST 1.1<br><br> - Have documented progressive disease (PD) within 12 weeks of the last dose of<br> anti PD 1/PD L1 mAb. Patients who were re-treated with anti PD 1/PD L1 mAb and<br> patients who were on maintenance with anti PD 1/PD L1 mAb will be allowed to<br> enter the trial as long as there is documented PD within 12 weeks of the last<br> treatment date (with anti PD 1/PD L1 mAb)<br><br> - Note - Subjects who have withdrawn from standard treatment due to<br> unacceptable toxicity warranting discontinuation of that treatment and<br> precluding retreatment with the same agent before progression of disease<br> will also be eligible<br><br>Exclusion Criteria:<br><br> - Subjects participating in or who have participated in a study of an investigational<br> agent or is using an investigational device within 4 weeks of the first dose of<br> study treatment or have received any anti-cancer therapy, platinum-based<br> chemotherapy, targeted, biological (including humanized antibodies),<br> investigational, immunotherapy, or hormonal agent, within 4 weeks of the first dose<br> of study treatment<br><br> - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any<br> other form of immunosuppressive therapy within 7 days prior to the first dose of<br> trial treatment<br><br> - Has had prior monoclonal antibody therapy within 4 weeks prior to study day 1 or who<br> has not recovered (i.e., =< grade 1 or at baseline) from adverse events (AEs) due to<br> agents administered more than 4 weeks earlier<br><br> - Has received previous treatment with an immunomodulatory therapy (eg, anti PD 1/PD<br> L1 or CTLA-4 agent) and was discontinued from that therapy due to a grade 3 or<br> higher immune-related adverse event (irAE)<br><br> - Had prior chemotherapy, targeted small molecule therapy within 4 weeks, or radiation<br> therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade<br> 1 or at baseline) from AEs due to a previously administered agent<br><br> - Note: subjects with =< grade 2 neuropathy are an exception to this criterion<br> and may qualify for the study<br><br> - Note: if a subject received major surgery, they must have recovered adequately<br> from the toxicity and/or complications from the intervention prior to starting<br> therapy<br><br> - Not

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

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