Neoantigen Vaccine Plus Locally Administered Ipilimumab and Systemic Nivolumab in Advanced Melanoma

NCT03929029 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: 18-2791R01CA229261
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is investigating a new type of personalized neoantigen vaccine, NeoVax, plus Montanide® in combination with Ipilimumab (Yervoy™) and Nivolumab (Opdivo®) as a possible treatment for cutaneous melanoma. The drugs involved in this study are:

• Personalized Neoantigen Vaccine
• Poly-ICLC (Hiltonol®)
• Montanide®
• Ipilimumab (Yervoy™)
• Nivolumab (Opdivo®)

Conditions

Cutaneous Melanoma

Keywords

Melanoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose-Limiting Toxicity (DLT)

  DLT (Protocol Section 5.5) definition: 1. Grade 3 or 4 toxicity that is definitely, probably, or possibly related to administration of vaccine, excluding transient (≤ 72 hours) flu-like symptoms; grade 3 nausea, vomiting, diarrhea, or constipation that returns to grade 2 (or lower) within 48 hours; any grade 3 rash that resolves to grade 2 or lower within 14 days; any grade 3 endocrine abnormality that is corrected with hormonal therapy within 4 weeks. 2. Grade 3 or 4 abnormal laboratory value that is at least possibly related to the administration of vaccine lasting for more than 7 days and requires hospitalization or medical intervention. Excludes any grade 3 electrolyte abnormality that: lasts ≤ 72 hours, is not clinically complicated, and resolves spontaneously or responds to conventional medical intervention. 3. Any grade 3 or grade 4 toxicity that is considered, in the opinion of the Principal Investigator, to be dose-limiting. 4. Any death related to study treatment.

  7 weeks after first dose of NeoVax

Secondary Outcomes (2)

• Number of Patients With Objective Response

  Up to 26 weeks after first administration of NeoVax

• Number of Patients With Disease Progression/Recurrence

  Up to 2 years

Study Arms (2)

Cohort 1: Nivolumab, NeoVax + Montanide, Ipilimumab 2.5 mg per injection site

EXPERIMENTAL

* Patients will receive Nivolumab at a 480 mg flat dose I.V. infusion every 4 weeks (28 days) * Patients will receive NeoVax plus Montanide injection on weeks 12, 15, 18, and 21 * Patients will receive concurrent Ipilimumab (2.5 mg per injection site) on weeks 12, 15, 18, and 21

Drug: Nivolumab (480 mg infusion); Biological: NeoVax plus Montanide; Drug: Ipilimumab

Cohort 2: Nivolumab, NeoVax + Montanide, Ipilimumab 5.0 mg per injection site

EXPERIMENTAL

* Patients will receive Nivolumab at a 480 mg flat dose I.V. infusion every 4 weeks (28 days) * Patients will receive NeoVax plus Montanide injection on weeks 12, 15, 18, and 21 * Patients will receive concurrent Ipilimumab (5.0 mg per injection site) on weeks 12, 15, 18, and 21

Drug: Nivolumab (480 mg infusion); Biological: NeoVax plus Montanide; Drug: Ipilimumab

Interventions

Nivolumab (480 mg infusion) DRUG

Nivolumab is an antibody that prevent cancer cells from suppressing the immune response so that the body can attack and kill the cancer

Also known as: Opdivo

Cohort 1: Nivolumab, NeoVax + Montanide, Ipilimumab 2.5 mg per injection site; Cohort 2: Nivolumab, NeoVax + Montanide, Ipilimumab 5.0 mg per injection site

NeoVax plus Montanide BIOLOGICAL

Montanide® is an activator of immunity that enhances response to vaccination through slow release of the peptides from the injection site and its ability to create an inflammation and stimulate the recruitment of specific cells of your immune system. Montanide® will be mixed with the personalized neoantigen vaccine

Cohort 1: Nivolumab, NeoVax + Montanide, Ipilimumab 2.5 mg per injection site; Cohort 2: Nivolumab, NeoVax + Montanide, Ipilimumab 5.0 mg per injection site

Ipilimumab DRUG

Ipilimumab is an antibody that prevent cancer cells from suppressing the immune response so that the body can attack and kill the cancer

Also known as: Yervoy

Cohort 1: Nivolumab, NeoVax + Montanide, Ipilimumab 2.5 mg per injection site; Cohort 2: Nivolumab, NeoVax + Montanide, Ipilimumab 5.0 mg per injection site

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is willing and able to give written informed consent
• Participants must have histologically confirmed cutaneous melanoma that is unresectable stage III or stage IV; at least one site of disease must be resectable, partially-resectable, or amenable to core biopsies to provide tumor tissue for sequence analysis. Participants with mucosal or uveal melanoma are excluded.
• Participants must have measurable disease by RECIST v1.1 that has not been treated with local therapy within the last 12 months of study treatment. The measurable lesion and the lesion used for surgical or core biopsies can be identical as long as it remains measurable after biopsy
• Age ≥ 18 years
• ECOG performance status of 0 or 1
• Participants must have normal organ and marrow function as defined below:
• WBC ≥3,000/µL
• ANC ≥1,500/µL
• Platelets ≥100,000/µL
• Hemoglobin ˃ 9.0 g/dL
• Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
• AST(SGOT)/ALT(SGPT) ≤ 3 x ULN
• Creatinine ≤ 1.5 x ULN OR
• Creatinine clearance ≥40 mL/min/1.73 m2 for participants with creatinine levels above institutional normal (if using the Cockcroft-Gault formula below):
• Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL

You may not qualify if:

• Prior immunotherapy for metastatic melanoma except anti-CTLA-4
• Concomitant therapy with any anti-cancer agents, other investigational anti-cancer therapies, or immunosuppressive agents including but not limited to methotrexate, chloroquine, azathioprine, etc. within six months of study participation
• Active brain metastases or leptomeningeal metastases
• Use of a non-oncology vaccine therapy for prevention of infectious diseases during the 4 week period prior to first dose of Nivolumab. Participants may not receive any non-oncology vaccine therapy during the period of Nivolumab or NeoVax plus Montanide administration and until at least 8 weeks after the last dose of study therapy
• History of severe allergic reactions attributed to any vaccine therapy for the prevention of infectious diseases
• Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• A condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring treatment, symptomatic
• 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
• Planned major surgery
• Pregnant women are excluded from this study because Nivolumab, personalized neoantigen peptides and poly-ICLC are agents with unknown risks to the developing fetus. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with Nivolumab, personalized neoantigen peptides and poly-ICLC, nursing women are excluded from this study
• Individuals with a history of an invasive malignancy are ineligible except for the following circumstances: a) individuals with a history of invasive malignancy are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; b) individuals with the following cancers are eligible if diagnosed and treated - carcinoma in situ of the breast, oral cavity or cervix, localized prostate cancer, basal cell or squamous cell carcinoma of the skin

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Dana-Farber Cancer Institute: lead

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; Monatide (IMS 3015); Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Small sample size.

Results Point of Contact

• Title: Dr. Patrick A. Ott
• Organization: Dana Farber Cancer Institute

patrick_ott@dfci.harvard.edu

6175829030

Study Officials

• Patrick A Ott, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 2, 2019
• First Posted: April 26, 2019
• Study Start: November 11, 2020
• Primary Completion: December 27, 2022
• Study Completion (Estimated): September 30, 2028
• Last Updated: January 5, 2026
• Results First Posted: October 31, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Requests may be directed to: \[contact information for Sponsor- Investigator or designee\].

Locations

US (1)