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
Overview
- Phase
- Phase 1
- Intervention
- Pembrolizumab
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Washington University School of Medicine
- Primary Endpoint
- Safety and feasibility of the combined regimen as measured by number of participants who experience a serious adverse event
- Status
- Withdrawn
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Detailed Description
Please note that this study originally opened with ID# 201707041 but was withdrawn due to change in standard of care chemotherapy.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#.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Cohort A: Histologically confirmed stage IV squamous NSCLC
- •Cohort B: Histologically confirmed extensive stage SCLC
- •Sufficient tumor tissue must be available for histologic assessment of PD-L1 expression and for sequence and immunological analysis.
- •Measurable disease by RECIST 1.
- •Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- •At least 18 years of age on the day of signing informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Normal bone marrow and organ function as defined in the table below within 10 days of study entry:
- •Absolute neutrophil count (ANC): ≥1500/µL
- •Platelets: ≥100 000/µL
Exclusion Criteria
- •Cohort A: Received any prior systemic therapy for cancer treatment.
- •Cohort B: May not have received more than one cycle of platinum doublet given with or without an anti-PD-1 or anti-PD-L1 immunotherapeutic.
- •Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days prior to day 1 or who has not recovered (ie, ≤ Grade 1 or at baseline from adverse events due to previous therapies). Patients with ≤Grade 2 neuropathy may be eligible.
- •Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
- •Received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- •Patients may not receive or have received any radiation therapy at the biopsy sites.
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- •Note: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- •Has had an allogeneic tissue/solid organ transplant.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy \> 10 mg prednisone daily or any other form of immunosuppressive therapy within 7 days prior to Day
Arms & Interventions
Cohort A: Stage IV squamous NSCLC
* 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
Intervention: Pembrolizumab
Cohort A: Stage IV squamous NSCLC
* 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
Intervention: NEO-PV-01 vaccine
Cohort A: Stage IV squamous NSCLC
* 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
Intervention: Biopsy
Cohort A: Stage IV squamous NSCLC
* 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
Intervention: Poly ICLC
Cohort A: Stage IV squamous NSCLC
* 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
Intervention: Leukapheresis
Cohort A: Stage IV squamous NSCLC
* 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
Intervention: Peripheral blood samples
Cohort B: Extensive stage SCLC
* 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
Intervention: Pembrolizumab
Cohort B: Extensive stage SCLC
* 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
Intervention: NEO-PV-01 vaccine
Cohort B: Extensive stage SCLC
* 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
Intervention: Biopsy
Cohort B: Extensive stage SCLC
* 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
Intervention: Poly ICLC
Cohort B: Extensive stage SCLC
* 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
Intervention: Leukapheresis
Cohort B: Extensive stage SCLC
* 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
Intervention: Peripheral blood samples
Outcomes
Primary Outcomes
Safety and feasibility of the combined regimen as measured by number of participants who experience a serious adverse event
Time Frame: 30 days following the completion of treatment (estimated to be 2 years and 16 weeks)
-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.
Secondary Outcomes
- Clinical benefit rate (CBR)(Through completion of treatment (estimated to be 108 weeks))
- Duration of response (DOR)(Through completion of treatment (estimated to be 108 weeks))
- Objective response rate (ORR) as measured per iRECIST(Through completion of treatment (estimated to be 108 weeks))
- Progression-free survival (PFS) as measured per iRECIST(Through completion of follow-up (estimated to be 7 years))
- Objective response rate as measured by RECIST 1.1(Through completion of treatment (estimated to be 108 weeks))
- Overall survival (OS)(Through completion of follow-up (estimated to be 7 years))
- Progression-free survival (PFS) as measured by RECIST 1.1(Through completion of follow-up (estimated to be 7 years))
- Response conversion rate (RCR)(Through completion of treatment (estimated to be 108 weeks))