NeoVax + CDX-301 and Nivolumab or Pembrolizumab in Melanoma

NCT04930783 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 21-066
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying the drugs called NeoVax (a new type of personalized neoantigen vaccine) in combination with CDX-301 and Nivolumab or Pembrolizumab as a possible treatment for melanoma. The names of the study drugs involved in this study are:

• Personalized Neoantigen peptides (which combined with poly-ICLC make the vaccine NeoVax)
• Poly-ICLC (Hiltonol)
• CDX-301
• Nivolumab (Opdivo)
• Pembrolizumab (Keytruda)

Conditions

Melanoma; Metastatic Melanoma

Keywords

Melanoma; Metastatic Melanoma

Outcome Measures

Primary Outcomes (2)

• Rate of Dose Limiting Toxicity (DLT)

  Based on the CTEP Active Version (version 5.0) of the NCI Common Terminology Criteria for Adverse Events (CTCAE).

  Toxicities experienced within 49 days/7 weeks of Neoantigen Vaccine treatment initiation

• Recommended maximum tolerated dose (MTD)

  Highest dose of CDX-301 that did not cause a dose limiting toxicity

  Up to 12 weeks for each dosing cohort

Secondary Outcomes (2)

• Neoantigen-specific cellular immune responses

  Enrollment to end of treatment up to 24 weeks

• Estimate rates of disease progression/recurrence depending on whether patient had all melanoma resected or has measurable disease per RECIST 1.1

  Enrollment to end of treatment up to 24 weeks

Study Arms (2)

CDX-301 + Neovax + Nivolumab

EXPERIMENTAL

* Participants will have vaccine made from tissue collected from metastatic tumor biopsy or surgical resection, or from previously collected archival biopsy or surgical tissue. * Participants will receive Nivolumab at a flat dose every 4 weeks up to two years. * Participants will receive CDX-301 at a predetermined dose dependent on the number of participants previously enrolled for 5 days starting 2 days before the initiation of NeoVax. CDX-301 will then be administered at a predetermined dose dependent on the number of participants previously enrolled 2 days before and for 5 days coinciding with the administration of NeoVax on days 50 and 78.

Drug: CDX-301; Biological: NEOVAX; Drug: Nivolumab

CDX-301 + Neovax + Pembrolizumab

EXPERIMENTAL

* Participants will have vaccine made from tissue collected from tumor biopsy, or from previously collected archival biopsy or surgical tissue. * Participants will receive neoadjuvant Pembrolizumab for 3 doses every 3 weeks, then undergo standard-of-care surgical resection. * Participants will receive adjuvant NeoVax and CDX-301. CDX-301 will be administered at a predetermined dose, dependent on the number of participants previously enrolled, for 5 days starting 2 days before the initiation of NeoVax. CDX-301 will then be administered at a predetermined dose dependent on the number of participants previously enrolled 2 days before and for 5 days coinciding with the administration of NeoVax on days 50 and 78. * Participants will receive adjuvant Pembrolizumab for 15 doses every 6 weeks.

Drug: CDX-301; Biological: NEOVAX; Drug: Pembrolizumab

Interventions

CDX-301 DRUG

Administered as an injection given underneath the skin

CDX-301 + Neovax + Nivolumab; CDX-301 + Neovax + Pembrolizumab

NEOVAX BIOLOGICAL

Personalized neoantigen vaccine administered as an injection given underneath the skin

CDX-301 + Neovax + Nivolumab; CDX-301 + Neovax + Pembrolizumab

Nivolumab DRUG

Administered intravenously (IV)

Also known as: Opdivo

CDX-301 + Neovax + Nivolumab

Pembrolizumab DRUG

Administered intravenously (IV)

Also known as: Keytruda

CDX-301 + Neovax + Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Eligibility to participate will be assessed at one timepoint: prior to initial core needle/surgical biopsy (Initial Registration).
• Participant is willing and able to give written informed consent
• Participants must have histologically confirmed stage IIIB/C/D or stage IV cutaneous melanoma (mucosal melanoma or uveal melanoma are excluded) that is surgically resected, is deemed surgically resectable, or is unresectable; tumor tissue for sequence analysis must be available from either previous melanoma resection/biopsy or at least one site of disease must be amenable to surgical or core 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 for anti-CTLA-4. Patients with unresectable melanoma who have received PD-1 inhibition therapy as adjuvant therapy and stopped receiving PD-1 inhibition for a period of ≥ 6 months before starting treatment with Nivolumab or Pembrolizumab are allowed to participate.
• 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 (with the exception of vaccination against the SARS-CoV-2 virus for the prevention of COVID-19 disease) during the 4 week period prior to first dose of Nivolumab or Pembrolizumab.
• Participants may not receive any non-oncology vaccine therapy during the period of Nivolumab (or Pembrolizumab) or NeoVax plus CDX-301 administration and until at least 8 weeks after the last dose of study therapy. Given the severity of the COVID-19 pandemic, vaccination specifically against the SARS-CoV-2 virus for the prevention of COVID-19 is ALLOWED in this study.
• 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. Corticosteroids used as pre-medication for imaging studies are allowed.
• 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).
• Known sensitivity or allergy to Nivolumab, Pembrolizumab, or CDX-301
• 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 (except for surgery for resection of melanoma if applicable).
• Patients with known mutations/amplifications in Flt-3

Sponsors & Collaborators

• Celldex Therapeutics: 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; pembrolizumab

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

Study Officials

• Patrick A Ott, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: June 18, 2021
• Study Start: January 3, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): September 30, 2030
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)