A Personal Cancer Vaccine (NEO-PV-01) and APX005M or Ipilimumab With Nivolumab in Patients With Advanced Melanoma

September 1, 2020 updated by: BioNTech US Inc.

An Open-label, Phase 1B Study of NEO-PV-01 + CD40 Agonist Antibody (APX005M) or Ipilimumab With Nivolumab in Patients With Advanced or Metastatic Melanoma

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.

Study Overview

Detailed Description

This clinical trial will enroll patients with advanced or metastatic melanoma not having received treatment for metastatic disease. The 5 agents being used in this study are:

  • A new, investigational, personal 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 APX005M, a drug that stimulates specific types of immune cells that help the immune system to recognize specific targets.
  • A cancer drug called ipilimumab
  • A cancer drug called nivolumab

NEO-PV-01, APX005M, ipilimumab, and nivolumab are considered immunotherapies and work using the immune system to fight cancer. NEO-PV-01 is a personal vaccine therapy in that it is manufactured specifically to include targets for the immune system that are present uniquely on your cancer. Poly-ICLC is an adjuvant that helps stimulate the immune system and make the vaccine, NEO-PV-01, more effective.

The purpose of this study is to find out if treatment with NEO-PV-01 + Poly-ICLC (the NEO-PV-01 vaccine) in combination with either APX005M or ipilimumab, and nivolumab is safe and useful for patients with melanoma. The study also will assess if the NEO-PV-01 vaccine, when given at different intervals, can improve your response compared with the standard schedule. This study will also assess the effects of poly-ICLC in combination with nivolumab. The side effects of all study drugs will be monitored and additional research tests will be done to assess your immune response to your cancer. There is no guarantee that you will benefit from therapy with the study drugs.

The FDA has not yet approved the NEO-PV-01 vaccine for use alone or in combination with other cancer drugs such as APX005M, ipilimumab, and nivolumab. Neither APX005M nor Poly-ICLC are approved for use in your type of cancer. Ipilimumab and nivolumab are both approved for use in your type of cancer.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • HonorHealth Research Institute
    • California
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles
    • Colorado
      • Denver, Colorado, United States, 80045
        • University of Colorado Denver
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • University of Utah, Huntsman Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.
  • 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 (e.g., 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 × 103/µL
    2. Platelet count ≥ 100 × 103/µL
    3. Hemoglobin > 9 g/dL
    4. Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for patients with liver metastases
    6. 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.
  • Male patients of childbearing potential must agree to use an adequate method of contraception, as outlined in the protocol, 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 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.

    1. Note: Patients with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study.
    2. 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.
  • Have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Have known active Hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C (e.g., hepatitis C virus [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.
  • Are 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 nivolumab, personalized neoantigen peptides, adjuvant, ipilimumab, and APX005M.
  • Have a history of additional invasive metastatic disease (other than melanoma), 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. Individuals with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or local papillary thyroid cancer, who have undergone therapy with curative intent.
  • Have severe hypersensitivity (≥ Grade 3) to nivolumab and/or any of its excipients.
  • Have mucosal melanoma, uveal melanoma, or acral lentiginous melanoma.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NEO-PV-01 + adjuvant + nivolumab
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.
Personal Cancer Vaccine
immune adjuvant
Other Names:
  • Hiltonol
  • Poly-ICLC
monoclonal antibody against PD-1
Other Names:
  • Opdivo
Experimental: Nivolumab + adjuvant
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.
immune adjuvant
Other Names:
  • Hiltonol
  • Poly-ICLC
monoclonal antibody against PD-1
Other Names:
  • Opdivo
Experimental: NEO-PV-01 + adjuvant + nivolumab on alternate schedule
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.
Personal Cancer Vaccine
immune adjuvant
Other Names:
  • Hiltonol
  • Poly-ICLC
monoclonal antibody against PD-1
Other Names:
  • Opdivo
Experimental: NEO-PV-01 + adjuvant + nivolumab + APX005M
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.
Personal Cancer Vaccine
immune adjuvant
Other Names:
  • Hiltonol
  • Poly-ICLC
monoclonal antibody against PD-1
Other Names:
  • Opdivo
monoclonal agonist antibody against CD40
Experimental: Nivolumab + APX005M
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.
monoclonal antibody against PD-1
Other Names:
  • Opdivo
monoclonal agonist antibody against CD40
Experimental: NEO-PV-01 + adjuvant + nivolumab + ipilimumab
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.
Personal Cancer Vaccine
immune adjuvant
Other Names:
  • Hiltonol
  • Poly-ICLC
monoclonal antibody against PD-1
Other Names:
  • Opdivo
monoclonal antibody against CTLA4
Other Names:
  • Yervoy
Experimental: Nivolumab + ipilimumab
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.
monoclonal antibody against PD-1
Other Names:
  • Opdivo
monoclonal antibody against CTLA4
Other Names:
  • Yervoy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The rate of adverse events and severe adverse events leading to treatment discontinuation
Time Frame: Baseline through 90 days after the last dose of nivolumab
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Baseline through 52 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
Baseline through 52 weeks
Clinical Benefit Rate
Time Frame: Baseline through 52 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
Baseline through 52 weeks
Duration of response
Time Frame: Baseline through 52 weeks
Duration of Response (DOR) defined as the date of the first documentation of a confirmed response to the date of the first documented progressive disease (PD) based on RECIST v1.1
Baseline through 52 weeks
Response conversion rate
Time Frame: Baseline through 52 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 to CR).
Baseline through 52 weeks
Progression free survival
Time Frame: Baseline through 52 weeks
Progression Free Survival (PFS), defined as the time from the date of first dosing to the date of first documented PD or death
Baseline through 52 weeks
Overall survival
Time Frame: Baseline through up to 3 years
Overall Survival (OS), defined from the date of enrollment and death from any cause
Baseline through up to 3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immune Responses
Time Frame: Baseline through 52 weeks
Antigen-specificity in peripheral CD8+ and CD4+ T cell responses and biomarker analyses of tumor biopsies following treatment
Baseline through 52 weeks
Overall response rate
Time Frame: Baseline through 52 weeks
To determine the anti-tumor activity, as assessed by ORR by iRECIST
Baseline through 52 weeks
Progression free survival
Time Frame: Baseline through 52 weeks
To determine the anti-tumor activity, as assessed by PFS by iRECIST
Baseline through 52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Study Director: Mark DeMario, MD, BioNTech US Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 8, 2018

Primary Completion (Actual)

May 5, 2020

Study Completion (Actual)

August 11, 2020

Study Registration Dates

First Submitted

July 13, 2018

First Submitted That Met QC Criteria

July 13, 2018

First Posted (Actual)

July 24, 2018

Study Record Updates

Last Update Posted (Actual)

September 3, 2020

Last Update Submitted That Met QC Criteria

September 1, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metastatic Melanoma

Clinical Trials on NEO-PV-01

3
Subscribe