NCT03597282

Brief Summary

The primary purpose of this study is to demonstrate that the NEO-PV-01 vaccine, either with APX005M or ipilimumab, and nivolumab is safe for the treatment of patients with advanced or metastatic melanoma. The study will also investigate an alternative schedule for the administration of the NEO-PV-01 vaccine. Study interventions will be assessed by both clinical and immune responses to treatment.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
22

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Oct 2018

Geographic Reach
1 country

8 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 13, 2018

Completed
11 days until next milestone

First Posted

Study publicly available on registry

July 24, 2018

Completed
3 months until next milestone

Study Start

First participant enrolled

October 8, 2018

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 5, 2020

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 11, 2020

Completed
Last Updated

September 3, 2020

Status Verified

September 1, 2020

Enrollment Period

1.6 years

First QC Date

July 13, 2018

Last Update Submit

September 1, 2020

Conditions

Keywords

Checkpoint InhibitorImmunotherapyPersonalized VaccineNeoantigenPOLY-ICLCPeptide

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 nivolumab

Secondary Outcomes (6)

  • Objective Response Rate (ORR)

    Baseline through 52 weeks

  • Clinical Benefit Rate

    Baseline through 52 weeks

  • Duration of response

    Baseline through 52 weeks

  • Response conversion rate

    Baseline through 52 weeks

  • Progression free survival

    Baseline through 52 weeks

  • +1 more secondary outcomes

Other Outcomes (3)

  • Immune Responses

    Baseline through 52 weeks

  • Overall response rate

    Baseline through 52 weeks

  • Progression free survival

    Baseline through 52 weeks

Study Arms (7)

NEO-PV-01 + adjuvant + nivolumab

EXPERIMENTAL

Nivolumab at a dose of 240 mg will be administered by intravenous infusion (IV) every 2 weeks throughout the study. At Week 12, all patients, regardless of their disease status, will receive NEO-PV-01 + adjuvant administered subcutaneously.

Biological: NEO-PV-01Biological: NivolumabOther: Adjuvant

Nivolumab + adjuvant

EXPERIMENTAL

Nivolumab at a dose of 240 mg will be administered by intravenous infusion (IV) every 2 weeks throughout the study. At Week 12, all patients, regardless of their disease status, will receive Poly-ICLC (adjuvant) administered subcutaneously.

Biological: NivolumabOther: Adjuvant

NEO-PV-01 + adjuvant + nivolumab on alternate schedule

EXPERIMENTAL

Nivolumab at a dose of 240 mg will be administered by intravenous infusion (IV) every 2 weeks throughout the study. At Week 12, all patients, regardless of their disease status, will receive NEO-PV-01 + adjuvant, administered on an alternative schedule, subcutaneously.

Biological: NEO-PV-01Biological: NivolumabOther: Adjuvant

NEO-PV-01 + adjuvant + nivolumab + APX005M

EXPERIMENTAL

Nivolumab at a dose of 240 mg will be administered by intravenous infusion (IV) every 2 weeks throughout the study. At Week 12, all patients, regardless of their disease status, will receive NEO-PV-01 + adjuvant administered subcutaneously. Patients on this arm will also receive APX005M at a dose of 0.1 mg/kg administered by IV infusion at Week 12, Week 15, and Week 19.

Biological: NEO-PV-01Biological: NivolumabOther: AdjuvantBiological: APX005M

Nivolumab + APX005M

EXPERIMENTAL

Nivolumab at a dose of 240 mg will be administered by intravenous infusion (IV) every 2 weeks throughout the study. At Week 12, Week 15, and Week 19, all patients, regardless of their disease status, will receive APX005M at a dose of 0.1 mg/kg administered by IV infusion.

Biological: NivolumabBiological: APX005M

NEO-PV-01 + adjuvant + nivolumab + ipilimumab

EXPERIMENTAL

Nivolumab at a dose of 240 mg administered by intravenous infusion (IV) every 2 weeks throughout the study. At Week 12, all patients, regardless of their disease status, will receive NEO-PV-01 + adjuvant administered subcutaneously. Patients on this arm will also receive ipilimumab at a dose of 1.0 mg/kg administered by IV infusion at Week 12 and Week 19.

Biological: NEO-PV-01Biological: NivolumabOther: AdjuvantBiological: ipilimumab

Nivolumab + ipilimumab

EXPERIMENTAL

Nivolumab at a dose of 240 mg will be administered by intravenous infusion (IV) every 2 weeks throughout the study. At Week 12 and Week 19, all patients, regardless of their disease status, will receive ipilimumab at a dose of 1.0 mg/kg administered by IV infusion.

Biological: NivolumabBiological: ipilimumab

Interventions

NEO-PV-01BIOLOGICAL

Personal Cancer Vaccine

NEO-PV-01 + adjuvant + nivolumabNEO-PV-01 + adjuvant + nivolumab + APX005MNEO-PV-01 + adjuvant + nivolumab + ipilimumabNEO-PV-01 + adjuvant + nivolumab on alternate schedule
NivolumabBIOLOGICAL

monoclonal antibody against PD-1

Also known as: Opdivo
NEO-PV-01 + adjuvant + nivolumabNEO-PV-01 + adjuvant + nivolumab + APX005MNEO-PV-01 + adjuvant + nivolumab + ipilimumabNEO-PV-01 + adjuvant + nivolumab on alternate scheduleNivolumab + APX005MNivolumab + adjuvantNivolumab + ipilimumab

immune adjuvant

Also known as: Hiltonol, Poly-ICLC
NEO-PV-01 + adjuvant + nivolumabNEO-PV-01 + adjuvant + nivolumab + APX005MNEO-PV-01 + adjuvant + nivolumab + ipilimumabNEO-PV-01 + adjuvant + nivolumab on alternate scheduleNivolumab + adjuvant
APX005MBIOLOGICAL

monoclonal agonist antibody against CD40

NEO-PV-01 + adjuvant + nivolumab + APX005MNivolumab + APX005M
ipilimumabBIOLOGICAL

monoclonal antibody against CTLA4

Also known as: Yervoy
NEO-PV-01 + adjuvant + nivolumab + ipilimumabNivolumab + ipilimumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Willing and able to give written informed consent.
  • Age ≥ 18 years.
  • Have cytologically or histologically confirmed advanced or metastatic melanoma and having received no prior systemic therapy for metastatic disease.
  • Have at least 1 site of disease measurable by RECIST 1.1 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.
  • Have at least 1 site of disease accessible to repeat biopsies for tumor sequencing and immunological analysis. This site may be a target lesion as long as it will not become unmeasurable by the biopsy procedure.
  • Have Eastern Cooperative Oncology Group Performance Status (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 × 103/µL
  • Platelet count ≥ 100 × 103/µL
  • Hemoglobin \> 9 g/dL
  • Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
  • 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).
  • Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days 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 the protocol, for the course of the study through 120 days after last dose of study medication.
  • +1 more criteria

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 advanced or metastatic cancer treatment including immunotherapeutic agents such as anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-CD40, or anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) antibody therapy.
  • Have had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AE due to agents administered more than 4 weeks earlier.
  • Have 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 AEs due to a previously administered agent.
  • Note: Patients with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study.
  • Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Received radiation therapy at the biopsy sites.
  • Received prior tyrosine kinase inhibitor therapy or palliative radiation within 7 days of Cycle 1/Day 1.
  • Have 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 \[using the identical imaging modality for each assessment, either magnetic resonance imaging (MRI) or computed tomography (CT) scan\] 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.
  • Have active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Have 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 vaccination within 30 days of planned treatment start date.
  • Have an active infection requiring systemic therapy.
  • Have a history of sensitivity or allergy to mAbs or immunoglobulin G (IgG).
  • Have a history of allogeneic bone marrow transplantation.
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of Colorado Denver

Denver, Colorado, 80045, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

NivolumabAdjuvants, Pharmaceuticpoly ICLCsotigalimabIpilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsPharmaceutic AidsPharmaceutical PreparationsSpecialty Uses of ChemicalsChemical Actions and Uses

Study Officials

  • Mark DeMario, MD

    BioNTech US Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 13, 2018

First Posted

July 24, 2018

Study Start

October 8, 2018

Primary Completion

May 5, 2020

Study Completion

August 11, 2020

Last Updated

September 3, 2020

Record last verified: 2020-09

Data Sharing

IPD Sharing
Will not share

Locations