Pembrolizumab and Nab-Paclitaxel in Treating Patients with Stage IV Non-small Cell Lung Cancer after First-Line Chemotherapy

Inclusion Criteria

• Be willing and able to provide written informed consent for the trial
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Histologically or cytologically confirmed stage IV (metastatic) NSCLC as defined by American Joint Committee on Cancer (AJCC); recurrent but not metastatic disease is allowed if deemed incurable
• Has completed or scheduled to begin 4-6 cycles of platinum-based induction chemotherapy that does not include a taxane * Induction may contain, but is not required to contain bevacizumab, necitumumab or cetuximab; induction with a platinum doublet plus another biologic agent will be allowed following review by the University of North Carolina (UNC) principal investigator (PI) that there is no additional risk to the subject * Day 1 (D1) of treatment on LCCC1516 must be 21-42 days from the last day of induction, consistent with timing of standard of care maintenance
• Documentation of target and non-target lesion(s) status per RECIST1.1 post induction chemotherapy for patients with evaluable disease * Note: Evaluable disease is not required for study entry (patients with complete response [CR] or response sufficient to preclude measurable lesions are not excluded; such patients will be evaluated for PFS and OS, but not for response)
• Absolute neutrophil count (ANC) >= 1,500 /mcL, performed within 14 days of treatment initiation
• Platelets >= 100,000 / mcL, performed within 14 days of treatment initiation
• Hemoglobin >= 10 g/dL (acceptable to reach this via transfusion), performed within 14 days of treatment initiation
• Calculated creatinine clearance >= 60 mL/min, performed within 14 days of treatment initiation
• Serum total bilirubin =< 1.5 X upper limit of normal (ULN) (=< 3 X ULN if Gilbert’s syndrome) OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN, performed within 14 days of treatment initiation
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN, performed within 14 days of treatment initiation
• 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, performed within 14 days of treatment initiation
• Activated partial thromboplastin time (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 anticoagulants, performed within 14 days of treatment initiation
• Recovered from all reversible toxicities related to their previous treatment (other than alopecia) to =< grade 1 or baseline
• Patients with brain metastases may participate if they have undergone appropriate treatment for the lesion(s), are at least two weeks post treatment without evidence for post-treatment progression, have no significant neurologic symptoms, and no longer require steroids for the reason of brain metastases
• 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 subjects of childbearing potential must be willing to use 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
• Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study

Exclusion Criteria

• Patients with EGFR mutations expected to be sensitive to EGFR inhibitors and patients with EML4/ALK translocations are excluded, unless all available Food and Drug Administration (FDA)-approved targeted therapy options have been utilized; for example, a patient with exon 19 EGFR mutation who has never been treated with an EGFR inhibitor would be excluded; patients with other sensitizing mutations that become actionable with FDA-approved targeted therapies during the course of this trial (e.g., crizotinib for MET deletion 14) will also be expected to have utilized all available FDA-approved targeted therapy options prior to eligibility * Note: In contrast to the above, a patient with an EGFR mutation who has been treated with a first-generation and third generation tyrosine kinase inhibitors (TKIs) and then with four cycles of carboplatin plus pemetrexed would be eligible
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 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
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1; 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 had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =<, grade 1 or at baseline and other than alopecia) from adverse events due to agents administered more than 4 weeks earlier; exceptions to these criteria may be allowed at the discretion of the UNC PI for toxicities that are not expected to be exacerbated by pembrolizumab or nab-paclitaxel
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren’s syndrome will not be excluded from the study
• Has a history of non-infectious pneumonitis that required steroids or evidence of interstitial lung disease or current active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• 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
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Had inadequate home environment or social support to safely complete the trial procedures
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Known hypersensitivity to protein bound paclitaxel
• Has received prior therapy with any taxane chemotherapy
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Has received a live vaccine within 30 days prior to the first dose of trial treatment