A Personal Cancer Vaccine (NEO-PV-01) With Pembrolizumab and Chemotherapy for Patients With Lung Cancer

NCT03380871 | Completed Phase 1 FDA Drug

• 1 other identifier: NT-002; KEYNOTE: MK-3475-779
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to find out if treatment with NEO-PV-01 in combination with pembrolizumab and chemotherapy (pembrolizumab/chemotherapy) is safe and useful for patients with lung cancer. The study also will assess if the NEO-PV-01 vaccine, when given together with pembrolizumab and chemotherapy, can improve your response compared with pembrolizumab and chemotherapy treatment alone. All eligible patients will receive NEO-PV-01 + Adjuvant, pembrolizumab and chemotherapy while on this trial.

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Cancer; Nonsquamous Nonsmall Cell Neoplasm of Lung

Keywords

Personal Vaccine; Neoantigen; Immunotherapy; Poly-ICLC; Peptide; Checkpoint Inhibitor

Outcome Measures

Primary Outcomes (1)

• The rate of adverse events and severe adverse events leading to treatment discontinuation

  Rate of adverse events and severe adverse events leading to treatment discontinuation and those adverse events and severe adverse events detected during symptom-directed physical examinations (changes in safety laboratory evaluations, physical examination findings. vital signs, and ECOG PS)

  Baseline through 90 days after the last dose of pembrolizumab

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  Baseline through 104 weeks

• Clinical Benefit Rate

  Baseline through 104 weeks

• Duration of Response

  Baseline through 104 weeks

• Response Conversion Rate

  Baseline to 104 weeks

• Progression Free Survival

  Baseline through 104 weeks

Other Outcomes (4)

• T Cell Immune Responses

  Day 1 of pembrolizumab/chemotherapy through 104 weeks

• Analysis of Tumor Biopsies

  Day 1 of pembrolizumab/chemotherapy through 104 weeks

• Overall Response Rate

  Baseline through 104 weeks

Study Arms (1)

NEO-PV-01/Adjuvant + pembrolizumab + chemotherapy

EXPERIMENTAL

Pembrolizumab at a dose of 200 mg administered by intravenous infusion (IV) plus chemotherapy with carboplatin (AUC 5) + pemetrexed (500 mg/m2) every 3 weeks for 4 cycles. At Week 12, all patients, regardless of their disease status, will receive NEO-PV-01 + adjuvant administered subcutaneously (one vial of pooled peptides per injection site) in up to four distinct sites (each extremity or flanks) while continuing therapy with pembrolizumab.

Biological: NEO-PV-01; Biological: Pembrolizumab; Other: Adjuvant; Drug: Carboplatin; Drug: Pemetrexed

Interventions

NEO-PV-01 BIOLOGICAL

Personal Cancer Vaccine

NEO-PV-01/Adjuvant + pembrolizumab + chemotherapy

Pembrolizumab BIOLOGICAL

monoclonal antibody against PDL1

Also known as: KEYTRUDA

NEO-PV-01/Adjuvant + pembrolizumab + chemotherapy

Adjuvant OTHER

immune adjuvant

Also known as: Hiltonol, Poly-ICLC

NEO-PV-01/Adjuvant + pembrolizumab + chemotherapy

Carboplatin DRUG

chemotherapy

NEO-PV-01/Adjuvant + pembrolizumab + chemotherapy

Pemetrexed DRUG

chemotherapy

Also known as: ALIMTA

NEO-PV-01/Adjuvant + pembrolizumab + chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give written informed consent.
• Have histologically confirmed unresectable or metastatic nonsquamous NSCLC and having received no prior systemic therapy for metastatic disease.
• Have at least 1 site of disease measurable by RECIST v1.1 that has not been treated with local therapy within 6 months of study treatment. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• At least 1 site of disease must be accessible to provide repeat biopsies for tumor tissue for sequence and immunological analysis. This site may be a target lesion as long as it will not be made unmeasurable by the biopsy procedure.
• Have ECOG PS of 0 or 1 with an anticipated life expectancy of \> 6 months.
• Screening laboratory values must meet the following criteria and should be obtained within 30 days (or 45 days if a biopsy is repeated) prior to study treatment:
• White blood cell (WBC) count ≥ 3 × 10e3/µL
• Absolute neutrophil count (ANC) ≥ 1.5 × 10e3/µL
• Platelet count ≥ 100 × 10e3/µL
• Hemoglobin \> 9 g/dL
• Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min/1.73 m2
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for patients with liver metastases
• Total bilirubin ≤ 1.5 × ULN (except in patients with Gilbert Syndrome who can have total bilirubin \< 3.0 mg/dL). Direct bilirubin ≤ ULN for patients with total bilirubin levels \>1.5 × ULN.
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of first dose of treatment.
• Received any systemic therapy for cancer treatment including immunotherapeutic agents such as anti-PD1 or anti-PD-L1 antibody therapy.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (ie, ≤ 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 30 days 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 or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Patients may not receive or have received any radiation therapy at the biopsy sites.
• Received radiation therapy to the lung \> 30 Gy within 6 months of first dose of study treatment.
• Received prior tyrosine kinase inhibitor therapy or palliative radiation within 7 days of first dose of study treatment.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging (using the identical imaging modality for each assessment, either MRI or CT scan) for at least 4 weeks prior to the first dose of trial treatment 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. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Patients may not receive any non-oncology vaccine therapy during the period of NEO PV-01 or pembrolizumab administration and until at least 8 weeks after the last dose of the booster vaccine. Seasonal influenza vaccines are allowed but may not be administered between the first dose of pembrolizumab and the last booster dose of NEO-PV-01
• Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to study Day 1.
• Has active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.

Sponsors & Collaborators

• BioNTech US Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

University of California - Los Angeles

Santa Monica, California, 90404, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

pembrolizumab; Adjuvants, Pharmaceutic; poly ICLC; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Mark DeMario, MD

  BioNTech US Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2017
• First Posted: December 21, 2017
• Study Start: May 4, 2018
• Primary Completion: October 31, 2019
• Study Completion: February 5, 2021
• Last Updated: February 26, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)