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Trial record 2 of 4 for:    neo-pv-01

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03380871
Recruitment Status : Active, not recruiting
First Posted : December 21, 2017
Last Update Posted : November 29, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
BioNTech SE

Tracking Information
First Submitted Date  ICMJE December 15, 2017
First Posted Date  ICMJE December 21, 2017
Last Update Posted Date November 29, 2019
Actual Study Start Date  ICMJE May 4, 2018
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 19, 2017)
The rate of adverse events and severe adverse events leading to treatment discontinuation [ Time Frame: Baseline through 90 days after the last dose of pembrolizumab ]
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2017)
  • Objective Response Rate (ORR) [ Time Frame: Baseline through 104 weeks ]
    Objective Response Rate (ORR), defined as the proportion of patients who achieve complete response (CR) or partial response (PR) based on Response Criteria in Solid Tumors (RECIST) v1.1
  • Clinical Benefit Rate [ Time Frame: Baseline through 104 weeks ]
    Clinical Benefit Rate (CBR), defined as the proportion of patients who achieve a CR, PR, or stable disease (SD) based on RECIST v1.1
  • Duration of Response [ Time Frame: Baseline through 104 weeks ]
    Duration of Response, DOR, defined as the date of the first documentation of a confirmed response to the date of the first documented PD based on RECIST v1.1
  • Response Conversion Rate [ Time Frame: Baseline to 104 weeks ]
    Response Conversion Rate (RCR), defined as the proportion of patients who improve in RECIST v1.1 category subsequent to vaccination (eg. PD to SD/PR/CR, SD to PR/CR, PR/CR).
  • Progression Free Survival [ Time Frame: Baseline through 104 weeks ]
    Progression Free Survival (PFS), defined as the time from the date of first dosing to the date of first documented PD or death
  • Overall Survival [ Time Frame: Baseline of pembrolizumab through 104 weeks ]
    Overall Survival (OS), defined from the date of enrollment and death from any cause
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: December 19, 2017)
  • T Cell Immune Responses [ Time Frame: Day 1 of pembolizumab/chemotherapy through 104 weeks ]
    Antigen-specificity in peripheral CD8+ and CD4+ T cell responses following treatment with NEO-PV-01, pembolizumab, and chemotherapy.
  • Analysis of Tumor Biopsies [ Time Frame: Day 1 of pembrolizumab/chemotherapy through 104 weeks ]
    Analysis of tumor biopsies following treatment of NEO-PV-01, pembrolizumab, and chemotherapy
  • Overall Response Rate [ Time Frame: Baseline through 104 weeks ]
    To determine the anti-tumor activity, as assessed by ORR by iRECIST
  • Progression Free Survival [ Time Frame: Baseline through 104 weeks ]
    To determine the anti-tumor activity, as assessed by PFS by iRECIST
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Personal Cancer Vaccine (NEO-PV-01) With Pembrolizumab and Chemotherapy for Patients With Lung Cancer
Official Title  ICMJE An Open-Label, Phase 1B Study of NEO-PV-01 With Pembrolizumab Plus Chemotherapy in Patients With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer
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.
Detailed Description

This clinical trial will enroll patients with advanced or metastatic nonsquamous non-small cell lung carcinoma not having received treatment for metastatic disease. The five agents being used in this study are:

  • A new, investigational, personalized cancer vaccine called "NEO-PV-01"
  • Poly-ICLC (Hiltonol), an investigational adjuvant that is used to help stimulate the immune system
  • A cancer drug called pembrolizumab (KEYTRUDA®)
  • A chemotherapy called pemetrexed (ALIMPTA®)
  • A chemotherapy called carboplatin

Both NEO-PV-01 and pembrolizumab are considered immunotherapies and work using the immune system to fight cancer. NEO-PV-01 is a custom made vaccine for you that is based on the specific targets on your cancer. Poly-ICLC is an adjuvant that helps stimulate the immune system and make the vaccine, NEO-PV-01, more effective.

Pembrolizumab helps T-cells, a certain type of immune cell, that recognize these targets to reach and attack your cancer. Pembrolizumab, which is approved in the USA and some other countries, is available by prescription to treat several different cancers, including the type of cancer that you have. Recently, the FDA also approved the combination of Pembrolizumab with chemotherapy for the treatment of your type of lung cancer. This combination works better than each of the drugs on their own.

The purpose of this study is to find out if treatment with NEO-PV-01 in combination with pembrolizumab and 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 immune response compared with pembrolizumab and chemotherapy treatment alone. The side effects of NEO-PV-01, pembrolizumab, and chemotherapy will be monitored and additional research tests will be done to assess your immune response to your cancer.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma, Non-Small-Cell Lung
  • Lung Cancer
  • Nonsquamous Nonsmall Cell Neoplasm of Lung
Intervention  ICMJE
  • Biological: NEO-PV-01
    Personal Cancer Vaccine
  • Biological: Pembrolizumab
    monoclonal antibody against PDL1
    Other Name: KEYTRUDA
  • Other: Adjuvant
    immune adjuvant
    Other Names:
    • Hiltonol
    • Poly-ICLC
  • Drug: Carboplatin
    chemotherapy
  • Drug: Pemetrexed
    chemotherapy
    Other Name: ALIMTA
Study Arms  ICMJE Experimental: NEO-PV-01/Adjuvant + pembrolizumab + chemotherapy
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.
Interventions:
  • Biological: NEO-PV-01
  • Biological: Pembrolizumab
  • Other: Adjuvant
  • Drug: Carboplatin
  • Drug: Pemetrexed
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: December 19, 2017)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2021
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.
  • Recovered from all toxicities associated with prior treatment to acceptable baseline status (for laboratory toxicities see below limits for inclusion) or a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03, Grade of 0 or 1, except for toxicities not considered a safety risk (eg, alopecia or vitiligo).
  • 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:

    1. White blood cell (WBC) count ≥ 3 × 10e3/µL
    2. Absolute neutrophil count (ANC) ≥ 1.5 × 10e3/µL
    3. Platelet count ≥ 100 × 10e3/µL
    4. Hemoglobin > 9 g/dL
    5. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min/1.73 m2
    6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for patients with liver metastases
    7. 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.
    8. 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
    9. 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
  • Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female patients of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 6.4.5.3, for the course of the study through 120 days after the last dose of study medication. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.
  • Male patients of childbearing potential must agree to use an adequate method of contraception as outlined in Section 6.4.5.3, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.

Exclusion Criteria:

  • 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.

    1. Note: Subjects with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study.
    2. 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.
  • Received a live-virus vaccination within 30 days of planned treatment start.
  • Have symptomatic ascites or pleural effusion.
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has a history of interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.
  • Have any underlying medical condition, psychiatric condition, or social situation that, in the opinion of the Investigator, would compromise study administration as per protocol or compromise the assessment of AEs.
  • Have a planned major surgery.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
  • Nursing women are excluded from this study because there is an unknown but potential risk of AEs in nursing infants secondary to treatment of the mother with pembrolizumab, personalized neoantigen peptides, and adjuvant.
  • Have a history of an invasive metastatic disease, except for the following:

    1. Individuals with a history of invasive metastatic disease are eligible if they have been disease free for at least 2 years and are deemed by the Investigator to be at low risk for recurrence of that metastatic disease;
    2. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Patients with nonsquamous NSCLC having functionally significant anaplastic lymphoma kinase (ALK) translocations or epidermal growth factor receptor (EGFR) mutations who have not received prior treatment with ALK or EGFR inhibitor.
  • Have severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03380871
Other Study ID Numbers  ICMJE NT-002; KEYNOTE: MK-3475-779
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party BioNTech SE
Study Sponsor  ICMJE BioNTech SE
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: Mark DeMario, MD Neon Therapeutics
PRS Account BioNTech SE
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP