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Personalized Therapeutic Anti-tumor Vaccine and Pembrolizumab in Treating Patients with Stage IV Non-small Cell Lung Cancer

Trial Status: In Review

This pilot phase I trial studies the side effects of personalized therapeutic anti-tumor vaccine and pembrolizumab in treating patients with stage IV non-small cell lung cancer. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving a personalized therapeutic anti-tumor vaccine and pembrolizumab may work better in treating patients with stage IV non-small cell lung cancer.

Inclusion Criteria

  • Histologically confirmed stage IV NSCLC (squamous, adenocarcinoma, or large cell carcinoma) that is stable or has partially responded after four cycles of a platinum doublet; (a complete response is not allowed) there is no restriction on prior lines of therapy; maintenance chemotherapy is not allowed
  • Sufficient tumor tissue must be available for histologic assessment of PD-L1 expression and whole exome sequencing
  • Measurable disease by RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Absolute neutrophil count >= 1,500/mcl
  • Platelets >= 100,000/mcl
  • Hemoglobin >= 9.0 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) OR direct bilirubin =< IULN for patients with total bilirubin > 1.5 x IULN
  • Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2.5 x IULN (or =< 5 x IULN for patients with liver metastases)
  • Albumin >= 2.5 mg/dL
  • Serum creatinine =< 1.5 x IULN OR creatinine clearance by Cockcroft-Gault >= 60 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 x IULN
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x IULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) =< 1.5 x IULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Sexually active women of childbearing potential and men must agree to use 2 methods of contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 120 days after last dose of pembrolizumab; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
  • Ability to understand and willingness to sign an Institutional Review Board (IRB), approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria

  • Patients with EGFR- or ALK-positive disease are not eligible for this study
  • Treatment with an anti-cancer monoclonal antibody within 4 weeks prior to day 1 or has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 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 are an exception to this criterion and may qualify for the study; NOTE: if subject received major surgery, s/he must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to day 1
  • Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Prior treatment with a cancer vaccine
  • Prior treatment with an anti-CTLA-4 agent
  • Received a live vaccine within 30 days prior to day 1
  • 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 day 1 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
  • Known carcinomatous meningitis
  • Currently receiving any other investigational agents or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to day 1
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or other agents used in the study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, underlying pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements
  • Has an active autoimmune disease requiring systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids (prednisone dose of 5 mg or less per day is allowed), or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Known history of, or any evidence of active, non-infectious pneumonitis
  • Pregnant and/or breastfeeding; patient must have a negative serum or urine pregnancy test within 72 hours of study entry
  • Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Known history of active tuberculosis (TB)
  • Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: IN_REVIEW
Contact: Ramaswamy Govindan
Phone: 314-362-5737

PRIMARY OBJECTIVES:

I. To investigate the safety and feasibility of the combination of a personalized tumor vaccine and pembrolizumab in non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To assess the clinical activity of the combination of a personalized tumor vaccine and pembrolizumab in NSCLC by measurement of the overall response rate and progression free survival based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, and overall survival.

II. To assess the clinical activity of the combination of a personalized tumor vaccine and pembrolizumab in NSCLC by measurement of the overall response rate and progression free survival based on immune-response related criteria (irRC).

III. To test the association of the number of predicted strong tumor associated mutant antigens and response.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of every course. Patients also receive personalized therapeutic anti-tumor vaccine subcutaneously (SC) on days 1, 4, 8, and 15 of course 1 and on day 1 of courses 2, 5, and 8. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, and then every 6 months for 3 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Ramaswamy Govindan

  • Primary ID 201901047
  • Secondary IDs NCI-2017-01314, 201707041
  • Clinicaltrials.gov ID NCT03166254