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Metastatic MelanomaPhase 1NCT03597282

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

A Phase 1 study testing NEO-PV-01, Nivolumab and Adjuvant in people with Metastatic Melanoma, run by BioNTech US Inc. at 8 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Melanoma
What is being tested?
NEO-PV-01, Nivolumab and Adjuvant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
8 sitesUnited States
Study dates
8 Oct 2018to 11 Aug 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • 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.
  • 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.

Who cannot join

  • 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.
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  • 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:
  • 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 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.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Colorado Denver

    Denver, Colorado, 80045

  • University of California, Los Angeles

    Los Angeles, California, 90095

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • University of Oklahoma

    Oklahoma City, Oklahoma, 73104

  • University of Utah, Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • HonorHealth Research Institute

    Scottsdale, Arizona, 85258

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
NEO-PV-01, Nivolumab, Adjuvant, APX005M, ipilimumab
Keywords
Checkpoint Inhibitor, Immunotherapy, Personalized Vaccine, Neoantigen, POLY-ICLC, Peptide
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NEO-PV-01Biological

    Personal Cancer Vaccine

  • NivolumabBiological

    Also called Opdivo

    monoclonal antibody against PD-1

  • AdjuvantOther

    Also called Hiltonol, Poly-ICLC

    immune adjuvant

  • APX005MBiological

    monoclonal agonist antibody against CD40

  • ipilimumabBiological

    Also called Yervoy

    monoclonal antibody against CTLA4

Study groups in NCT03597282
Study groupRoleWhat they receive
NEO-PV-01 + adjuvant + nivolumabExperimentalNivolumab 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.
Receives: Biological: NEO-PV-01; Biological: Nivolumab; Other: Adjuvant
Nivolumab + adjuvantExperimentalNivolumab 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.
Receives: Biological: Nivolumab; Other: Adjuvant
NEO-PV-01 + adjuvant + nivolumab on alternate scheduleExperimentalNivolumab 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.
Receives: Biological: NEO-PV-01; Biological: Nivolumab; Other: Adjuvant
NEO-PV-01 + adjuvant + nivolumab + APX005MExperimentalNivolumab 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.
Receives: Biological: NEO-PV-01; Biological: Nivolumab; Other: Adjuvant; Biological: APX005M
Nivolumab + APX005MExperimentalNivolumab 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.
Receives: Biological: Nivolumab; Biological: APX005M
NEO-PV-01 + adjuvant + nivolumab + ipilimumabExperimentalNivolumab 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.
Receives: Biological: NEO-PV-01; Biological: Nivolumab; Other: Adjuvant; Biological: ipilimumab
Nivolumab + ipilimumabExperimentalNivolumab 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.
Receives: Biological: Nivolumab; Biological: ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: Baseline through 90 days after the last dose of nivolumab

Secondary outcomes (6)

  1. Objective Response Rate (ORR)

    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

    Measured: Baseline through 52 weeks

  2. Clinical Benefit Rate

    Clinical Benefit Rate (CBR), defined as the proportion of patients who achieve a CR, PR, or stable disease (SD) based on RECIST v1.1

    Measured: Baseline through 52 weeks

  3. Duration of response

    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

    Measured: Baseline through 52 weeks

  4. Response conversion rate

    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).

    Measured: Baseline through 52 weeks

  5. Progression free survival

    Progression Free Survival (PFS), defined as the time from the date of first dosing to the date of first documented PD or death

    Measured: Baseline through 52 weeks

  6. Overall survival

    Overall Survival (OS), defined from the date of enrollment and death from any cause

    Measured: Baseline through up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jul 2018
  2. Study start8 Oct 2018
  3. Primary completion5 May 2020
  4. Study completion11 Aug 2020

Why it stopped: Closed due to historically slow enrollment compounded by the COVID-19 pandemic.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03597282
Sponsor's protocol ID
NT-003
Status last verified
Sep 2020
First submitted
13 Jul 2018
Last updated
3 Sep 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing NEO-PV-01, Nivolumab and Adjuvant in people with Metastatic Melanoma, run by BioNTech US Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Closed due to historically slow enrollment compounded by the COVID-19 pandemic.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03597282.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2020.

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