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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
1 other identifier
interventional
N/A
0 countries
N/A
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Apr 2019
Longer than P75 for phase_1
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 23, 2017
CompletedFirst Posted
Study publicly available on registry
May 25, 2017
CompletedStudy Start
First participant enrolled
April 30, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
May 31, 2027
ExpectedApril 12, 2019
April 1, 2019
3.2 years
May 23, 2017
April 10, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Safety and feasibility of the combined regimen as measured by number of participants who experience a serious adverse event
-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.
30 days following the completion of treatment (estimated to be 2 years and 16 weeks)
Secondary Outcomes (8)
Objective response rate as measured by RECIST 1.1
Through completion of treatment (estimated to be 108 weeks)
Progression-free survival (PFS) as measured by RECIST 1.1
Through completion of follow-up (estimated to be 7 years)
Overall survival (OS)
Through completion of follow-up (estimated to be 7 years)
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)
- +3 more secondary outcomes
Study Arms (2)
Cohort A: Stage IV squamous NSCLC
EXPERIMENTAL* 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
Cohort B: Extensive stage SCLC
EXPERIMENTAL* 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
Interventions
-Pembrolizumab will be given intravenously over the course of 30 minutes
-Generation of the vaccine is expected to take approximately 12 weeks
-Surgical or core needle biopsy of an accessible site for DNA and RNA sequencing, immunological analysis, and generation of NEO-PV-01 vaccine
-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.
-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.
Eligibility Criteria
You may qualify if:
- 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 1.1. 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
- Hemoglobin: ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks)
- Creatinine: ≤1.5 × upper limit of normal (ULN) OR
- Measured or calculated2 creatinine clearance (GFR can also be used in place of creatinine or CrCl): ≥30 mL/min for patient with creatinine levels / \>1.5 × institutional ULN
- Total bilirubin: ≤1.5 ×ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels \>1.5 × ULN
- AST (SGOT) and ALT (SGPT): ≤2.5 × ULN (≤5 × ULN for patients with liver metastases)
- International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (aPTT): ≤1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
- +3 more criteria
You may not qualify if:
- 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 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 agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
- Received a live vaccine within 30 days prior to Day 1. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Known active 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.
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Washington University School of Medicinelead
- Merck Sharp & Dohme LLCcollaborator
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ramaswamy Govindan, M.D.
Washington University School of Medicine
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 23, 2017
First Posted
May 25, 2017
Study Start
April 30, 2019
Primary Completion
June 30, 2022
Study Completion (Estimated)
May 31, 2027
Last Updated
April 12, 2019
Record last verified: 2019-04