Clinical Trial - NCT03597282

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

Recruiting

Sponsor: Neon Therapeutics, Inc.

Collaborators: Apexigen, Inc.

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03597282

Protocol Info

Short Description: Phase 1B NEO-PV-01 + APX005M or Ipilimumab + Nivolumab in Melanoma
Long Description: 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
MGH Status: Open
Sponsor: Neon Therepeutics
Disease Program: Melanoma

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

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 Title Intervention Phase
Metastatic Melanoma NEO-PV-01 Nivolumab Adjuvant APX005M ipilimumab Phase 1
Study Type Interventional
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

Primary Outcome Measures

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] [Designated as safety issue: ]


Secondary Outcome Measures

Objective Response Rate (ORR) [Time Frame: Baseline through 52 weeks] [Designated as safety issue: ]

Clinical Benefit Rate [Time Frame: Baseline through 52 weeks] [Designated as safety issue: ]

Duration of response [Time Frame: Baseline through 52 weeks] [Designated as safety issue: ]

Response conversion rate [Time Frame: Baseline through 52 weeks] [Designated as safety issue: ]

Progression free survival [Time Frame: Baseline through 52 weeks] [Designated as safety issue: ]

Overall survival [Time Frame: Baseline through up to 3 years] [Designated as safety issue: ]

Estimated Enrollment: 40
Study Start Date: October 2018
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: September 2020
Arms Assigned Interventions

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.
Other:Adjuvant
immune adjuvant

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.

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.

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: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.

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:ipilimumab
monoclonal antibody against CTLA4

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.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03597282

Locations

  • United States, Arizona
    • HonorHealth Research Institute Scottsdale, Arizona, United States, 85258
  • United States, California
    • University of California, Los Angeles Los Angeles, California, United States, 90095
  • United States, Colorado
    • University of Colorado Denver Denver, Colorado, United States, 80045
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Ohio
    • The Christ Hospital Cincinnati, Ohio, United States, 45219
    • University of Toledo Medical Center Toledo, Ohio, United States, 43614
  • United States, Oklahoma
    • University of Oklahoma Oklahoma City, Oklahoma, United States, 73104
  • United States, Pennsylvania
    • Sidney Kimmel Cancer Center at Thomas Jefferson University Philadelphia, Pennsylvania, United States, 19107
  • United States, Tennessee
    • Sarah Cannon Research Institute Nashville, Tennessee, United States, 37203

Sponsors and Collaborators

Neon Therapeutics, Inc.

Apexigen, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03597282
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Neon Therapeutics, Inc.:

Checkpoint Inhibitor

Immunotherapy

Personalized Vaccine

Neoantigen

POLY-ICLC

Peptide

Additional relevant MeSH terms:

Melanoma

Vaccines

Antibodies

Poly ICLC

Nivolumab

Ipilimumab

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019