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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03597282
Recruitment Status : Recruiting
First Posted : July 24, 2018
Last Update Posted : October 17, 2019
Sponsor:
Collaborator:
Apexigen, Inc.
Information provided by (Responsible Party):
Neon Therapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Biological: NEO-PV-01 Biological: Nivolumab Other: Adjuvant Biological: APX005M Biological: ipilimumab Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 8, 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

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.
Biological: NEO-PV-01
Personal Cancer Vaccine

Biological: Nivolumab
monoclonal antibody against PD-1
Other Name: Opdivo

Other: Adjuvant
immune adjuvant
Other Names:
  • Hiltonol
  • Poly-ICLC

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.
Biological: Nivolumab
monoclonal antibody against PD-1
Other Name: Opdivo

Other: Adjuvant
immune adjuvant
Other Names:
  • Hiltonol
  • Poly-ICLC

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.
Biological: NEO-PV-01
Personal Cancer Vaccine

Biological: Nivolumab
monoclonal antibody against PD-1
Other Name: Opdivo

Other: Adjuvant
immune adjuvant
Other Names:
  • Hiltonol
  • Poly-ICLC

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.
Biological: NEO-PV-01
Personal Cancer Vaccine

Biological: Nivolumab
monoclonal antibody against PD-1
Other Name: Opdivo

Other: Adjuvant
immune adjuvant
Other Names:
  • Hiltonol
  • Poly-ICLC

Biological: APX005M
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.
Biological: Nivolumab
monoclonal antibody against PD-1
Other Name: Opdivo

Biological: APX005M
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.
Biological: NEO-PV-01
Personal Cancer Vaccine

Biological: Nivolumab
monoclonal antibody against PD-1
Other Name: Opdivo

Other: Adjuvant
immune adjuvant
Other Names:
  • Hiltonol
  • Poly-ICLC

Biological: ipilimumab
monoclonal antibody against CTLA4
Other Name: 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.
Biological: Nivolumab
monoclonal antibody against PD-1
Other Name: Opdivo

Biological: ipilimumab
monoclonal antibody against CTLA4
Other Name: Yervoy




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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).

  5. 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

  6. Overall survival [ Time Frame: Baseline through up to 3 years ]
    Overall Survival (OS), defined from the date of enrollment and death from any cause


Other Outcome Measures:
  1. 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

  2. Overall response rate [ Time Frame: Baseline through 52 weeks ]
    To determine the anti-tumor activity, as assessed by ORR by iRECIST

  3. Progression free survival [ Time Frame: Baseline through 52 weeks ]
    To determine the anti-tumor activity, as assessed by PFS by iRECIST



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03597282


Contacts
Layout table for location contacts
Contact: April Lamb 617-337-4724 alamb@neontherapeutics.com
Contact: Lisa Cleary 617-337-4715 lcleary@neontherapeutics.com

Locations
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United States, Arizona
HonorHealth Research Institute Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Joyce Schaffer    480-323-1339    clinicaltrials@honorheath.com   
Principal Investigator: Michael Gordon, MD         
United States, California
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: James Ho    310-794-3102    jamesho@mednet.ucla.edu   
Principal Investigator: Bartosz Chmielowski, MD         
United States, Colorado
University of Colorado Denver Recruiting
Denver, Colorado, United States, 80045
Contact: Michelle Landis    720-848-7135    michelle.landis@ucdenver.edu   
Principal Investigator: Karl Lewis, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Ryan J Sullivan, MD    617-724-4000    Rsullivan7@partners.org   
Principal Investigator: Ryan J Sullivan, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Jennifer Maattala    617-632-3992    Jennifera_maattala@dfci.harvard.edu   
Principal Investigator: Patrick Ott, MD, PhD         
United States, Ohio
The Christ Hospital Withdrawn
Cincinnati, Ohio, United States, 45219
University of Toledo Medical Center Withdrawn
Toledo, Ohio, United States, 43614
United States, Oklahoma
University of Oklahoma Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Dena Suthers    405-271-8778 ext 2    Phasel-Refferals@ouhsc.edu   
Principal Investigator: Alexandra Ikeguchi, MD         
United States, Pennsylvania
Sidney Kimmel Cancer Center at Thomas Jefferson University Withdrawn
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact    615-339-4214    asksarah@sarahcannon.com   
Principal Investigator: David Spigel, MD         
United States, Utah
University of Utah, Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Elizabeth Constantz, CCRP    801-587-4567    elizabeth.constantz@hci.utah.edu   
Principal Investigator: Siwen Hu-Lieskovan, MD, PHD         
Sponsors and Collaborators
Neon Therapeutics, Inc.
Apexigen, Inc.
Investigators
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Study Director: Andrew Chi, MD, PhD Neon Therapeutics

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Responsible Party: Neon Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03597282     History of Changes
Other Study ID Numbers: NT-003
First Posted: July 24, 2018    Key Record Dates
Last Update Posted: October 17, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Neon Therapeutics, Inc.:
Checkpoint Inhibitor
Immunotherapy
Personalized Vaccine
Neoantigen
POLY-ICLC
Peptide
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Nivolumab
Ipilimumab
Vaccines
Antibodies
Poly ICLC
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents
Interferon Inducers