A Personal Cancer Vaccine (NEO-PV-01) w/ Nivolumab for Patients With Melanoma, Lung Cancer or Bladder Cancer

NCT02897765 | Completed Phase 1

• 1 other identifier: NT-001
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to evaluate if the treatment with NEO-PV-01 + adjuvant in combination with nivolumab is safe and useful for patients with certain types of cancer. The study also will investigate if NEO-PV-01 + adjuvant with nivolumab may represent a substantial improvement over other available therapies such as nivolumab alone. All eligible patients will receive NEO-PV-01 + adjuvant and nivolumab while on this trial.

Conditions

Urinary Bladder Cancer; Bladder Tumors; Transitional Cell Carcinoma of the Bladder; Malignant Melanoma; Melanoma; Skin Cancer; Carcinoma, Non-Small-Cell Lung; Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (5)

• Rate of adverse events including SAEs and AEs leading to treatment discontinuation

  Rate of adverse events including SAEs and AEs leading to treatment discontinuation

  Baseline through 100 days after last dose of nivolumab

• Rate of adverse events including SAEs and AEs leading to changes in safety laboratory evaluations

  Rate of adverse events including SAEs and AEs leading to changes in safety laboratory evaluations

  Baseline through 100 days after last dose of nivolumab

• Rate of adverse events including SAEs and AEs leading to physical examination findings

  Rate of adverse events including SAEs and AEs leading to physical examination findings

  Baseline through 100 days after last dose of nivolumab

• Rate of adverse events including SAEs and AEs leading to vital signs findings

  Rate of adverse events including SAEs and AEs leading to vital signs findings

  Baseline through 100 days after last dose of nivolumab

• Rate of adverse events including SAEs and AEs leading to changes in ECOG status

  Rate of adverse events including SAEs and AEs leading to changes in ECOG status

  Baseline through 100 days after last dose of nivolumab

Secondary Outcomes (6)

• Objective response rate (ORR)

  Baseline through 104 weeks

• Duration of response (DOR)

  Baseline through 104 weeks

• Clinical benefit rate (CBR)

  Baseline through 104 weeks

• Response conversion rate (RCR)

  Baseline through 104 weeks

• Progression-free survival (PFS)

  Baseline through 104 weeks

Other Outcomes (1)

• Immune Responses

  Day 1 of nivolumab through 104 weeks

Study Arms (1)

Drug: NEO-PV-01 + Nivolumab + Adjuvant

EXPERIMENTAL

Nivolumab at a dose of 240 mg administered by intravenous (IV) infusion over 30 minutes every two weeks. 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 nivolumab.

Biological: NEO-PV-01; Biological: Nivolumab; Other: Adjuvant

Interventions

NEO-PV-01 BIOLOGICAL

Personal cancer vaccine

Also known as: Personal cancer vaccine

Drug: NEO-PV-01 + Nivolumab + Adjuvant

Nivolumab BIOLOGICAL

monoclonal antibody against PD1

Also known as: Opdivo

Drug: NEO-PV-01 + Nivolumab + Adjuvant

Adjuvant OTHER

immune adjuvant

Also known as: Hiltonol, poly-ICLC

Drug: NEO-PV-01 + Nivolumab + Adjuvant

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 melanoma having received no more than one prior systemic therapy for the metastatic disease (eg. ipilumamab and/or BRAF inhibitor); unresectable or metastatic smoking-associated NSCLC having received no more than one prior systemic therapy for the metastatic disease (eg standard of care chemotherapy, as appropriate); unresectable or metastatic transitional cell carcinoma of the bladder, urethra, ureter or renal pelvis having received no more than one prior systemic therapy for the metastatic disease.
• Have at least one site of disease measurable disease by RECIST v1.1 that has not been treated with local therapy within 6 months of study treatment. This can be the site for initial or repeat biopsies as long as it will remain measurable following biopsy.
• At least one site of disease must be accessible to provide repeat biopsies for tumor tissue for sequence and immunological analysis.
• Have ECOG PS of 0 or 1 with an anticipated life expectancy of \> 6 months.
• Age ≥ 18 years.
• Screening laboratory values must meet the following criteria and should be obtained within 30 days (45 if biopsy is repeated) prior to study treatment:
• White blood cell (WBC) count ≥ 3 × 10e3/µL
• Absolute neutrophil count (ANC) ≥ 1.5 × 10e3/µL
• Absolute lymphocyte count (ALC) ≥ 1 × 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 m
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN
• Total bilirubin ≤ 1.5 × ULN (except in patients with Gilbert Syndrome who can have total bilirubin \< 3.0 mg/dL).

You may not qualify if:

• Received therapy with any immunotherapeutic agents including, but not limited to, any anti-PD1 or anti-PDL1 antibody therapy, with these exceptions: Melanoma patients having received and progressed on anti-CTLA4 (cyctotoxic T lymphocyte-associated antigen 4) may participate in the trial; Bladder cancer patients having received intra-vesical BCG may participate in the trial.
• Received systemic anti-cancer therapy within 30 days of Week 0, Day 11 of study treatment.
• Have untreated central nervous system (CNS) metastases. Patients are eligible for study participation if CNS metastases are adequately treated and patients are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 60 days prior to consent. In addition, patients must either be off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) for at least 60 days prior to consent.
• Received non-oncology vaccine therapy for prevention of infectious diseases during the 4-week period prior to first dose of nivolumab therapy. Patients may not receive any non-oncology vaccine therapy during the period of NEO-PV-01 + adjuvant or nivolumab administration and until at least 8 weeks after the last dose of the booster vaccine. Annual influenza vaccines are allowed during screening and pre-treatment but not during nivolumab or NEO-PV-01 + adjuvant dosing.
• Received radiation therapy within 4 weeks prior to Week 0, Day 1 of study treatment. Patients may not receive or have received any radiation therapy at the biopsy sites.
• Have an active or history of autoimmune disease (known or suspected). Exceptions are permitted for vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition requiring only hormone replacement, psoriasis not on systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 15 days prior to the first dose of study treatment (nivolumab). Inhaled or topical steroids and adrenal replacement doses (≤ 10 mg daily prednisone equivalents) are permitted in the absence of active autoimmune disease.
• Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C, or life-threatening illnesses unrelated to cancer.
• Have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring treatment, symptomatic congestive heart failure, unstable angina pectoris, or 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.
• Pregnant women are excluded from this study because nivolumab, personalized neoantigen peptides, and Poly-ICLC are agents with unknown risks to the developing fetus.
• Nursing women are excluded from this study because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with nivolumab, personalized neoantigen peptides, and Poly-ICLC.
• Have a history of an invasive metastatic disease, except for the following circumstances: 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; individuals with the following cancers are eligible if diagnosed and treated: carcinoma in situ of the breast, oral cavity or cervix, localized prostate cancer, basal cell or squamous cell carcinoma of the skin.
• Mucosal melanoma and uvueal melanoma.

Sponsors & Collaborators

• BioNTech US Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (9)

City of Hope

Duarte, California, 91010, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Center

Boston, Massachusetts, 02115, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Poran A, Scherer J, Bushway ME, Besada R, Balogh KN, Wanamaker A, Williams RG, Prabhakara J, Ott PA, Hu-Lieskovan S, Khondker ZS, Gaynor RB, Rooney MS, Srinivasan L. Combined TCR Repertoire Profiles and Blood Cell Phenotypes Predict Melanoma Patient Response to Personalized Neoantigen Therapy plus Anti-PD-1. Cell Rep Med. 2020 Nov 17;1(8):100141. doi: 10.1016/j.xcrm.2020.100141. eCollection 2020 Nov 17.

  PMID: 33294862 DERIVED

• Ott PA, Hu-Lieskovan S, Chmielowski B, Govindan R, Naing A, Bhardwaj N, Margolin K, Awad MM, Hellmann MD, Lin JJ, Friedlander T, Bushway ME, Balogh KN, Sciuto TE, Kohler V, Turnbull SJ, Besada R, Curran RR, Trapp B, Scherer J, Poran A, Harjanto D, Barthelme D, Ting YS, Dong JZ, Ware Y, Huang Y, Huang Z, Wanamaker A, Cleary LD, Moles MA, Manson K, Greshock J, Khondker ZS, Fritsch E, Rooney MS, DeMario M, Gaynor RB, Srinivasan L. A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer. Cell. 2020 Oct 15;183(2):347-362.e24. doi: 10.1016/j.cell.2020.08.053.

  PMID: 33064988 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Melanoma; Skin Neoplasms; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Nivolumab; Adjuvants, Pharmaceutic; poly ICLC

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

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: August 12, 2016
• First Posted: September 13, 2016
• Study Start: October 1, 2016
• Primary Completion: February 1, 2019
• Study Completion: May 1, 2020
• Last Updated: February 25, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)