Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Small Cell Lung Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Pembrolizumab

Vaccines

Poly ICLC

Immunologic Factors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Interferons

* 4 cycles of standard of care (SOC) platinum doublet chemotherapy (investigator's choice)
* Pembrolizumab (200 mg every 3 weeks (Q3W) for 4 cycles while patient is receiving SOC chemo). Pembrolizumab may continue to be administered Q3W for a maximum of 35 total administrations
* All patients will begin the NEO-PV-01 vaccination at Week 12, 3 weeks following the 4th cycle of pembrolizumab / chemotherapy. At Week 12 (Cycle 5), NEO-PV-01 vaccinations will be administered in a prime-boost schedule with 5 priming vaccinations over a 3 week period followed by booster vaccinations at 1 month and 2 months after the last priming vaccination
* Up to 20 personalized vaccine peptides will be administered for each patient. Vaccine administration will occur on Days 1, 4, 8, 15 during Cycle 5 of pembrolizumab administration and Day 1 of Cycle 6 of pembrolizumab administration, on Day 8 during Cycle 7 of pembrolizumab administration, and on Day 15 during Cycle 8 of pembrolizumab administration

-Pembrolizumab will be given intravenously over the course of 30 minutes

-Generation of the vaccine is expected to take approximately 12 weeks

NEO-PV-01 vaccine

-Surgical or core needle biopsy of an accessible site for DNA and RNA sequencing, immunological analysis, and generation of NEO-PV-01 vaccine

Biopsy

-NEO-PV-01 is combined with the adjuvant poly-ICLC prior to administration.

-Peripheral blood mononuclear cells (PBMCs) for comprehensive immune system monitoring will be obtained from leukapheresis samples collected up to 7 days prior to initiation of NEO PV-01 vaccination and at 7 days (Week 20) following the first NEO-PV-01 booster vaccination.

Leukapheresis

-Blood samples (80 mL) for immune monitoring will be obtained prior to study treatment and at Weeks 6, 14, 16, 24, 36, 48, 63, 75, 87, and 99.

Peripheral blood samples

Ramaswamy Govindan, M.D.

Both metastatic squamous non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (SCLC) are incurable with current therapies, but due to mutations induced by cigarette smoke, typically express a large number of altered proteins that can be recognized as foreign by the immune system. This antigenicity is thought to explain the efficacy of pembrolizumab as either a first or second line treatment in this disease. For patients who receive chemotherapy plus immunotherapy as a first line therapy, there is sound rationale for combination treatment with immunotherapy and a therapeutic antitumor vaccine as a maintenance strategy. Regardless of PD-L1 expression in the tumor, monoclonal antibodies that block PD-1/PD-L1 interactions are effective second line therapies after chemotherapy in both NSCLC and SCLC. In addition, by targeting the immune system against tumor specific antigens using a peptide vaccine, the efficacy of pembrolizumab alone is expected to be enhanced, with an improved response rate and prolonged overall survival with no additional toxicity.

This pilot study will provide a preliminary test of the feasibility of generating a personalized, tumor neoantigen-specific therapeutic vaccine and the safety of combining it with checkpoint blockade immunotherapy.

Please note that this study originally opened with ID# 201707041 but was withdrawn due to change in standard of care chemotherapy. This study was revised and submitted as an amendment to the same IND but our IRB required it to be submitted as a new study and it received a new ID#.

Personalized Therapeutic Anti-tumor Vaccine With Pembrolizumab and Standard of Care Chemotherapy in Squamous Non-Small Cell Lung Cancer and Extensive Stage Small Cell Lung Cancer

Pilot Feasibility Study of the Combination of a Personalized Therapeutic Anti-tumor Vaccine With Pembrolizumab and Standard of Care Chemotherapy in Squamous Non-Small Cell Lung Cancer and Extensive Stage Small Cell Lung Cancer

-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

--Percentage of participants who experience a complete or partial response

* Complete Response (CR): Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm
* Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters

* PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
* Progressive disease: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

-PFS is defined as the duration of time from start of personalized vaccine treatment (\~12 weeks after baseline) to time of progression or death, whichever occurs first.

Spots Global Cancer Trial Database for small cell lung extensive stage