A Phase I Study With a Personalized NeoAntigen Cancer Vaccine in Melanoma

NCT01970358 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 13-240
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is evaluating a new type of melanoma vaccine called "Personalized NeoAntigen Cancer Vaccine". The purpose of this study is to determine if it is possible to make and administer safely a vaccine against melanoma by using information gained from specific characteristics of the participant's own melanoma. It is known that melanomas have mutations (changes in genetic material) that are specific to an individual patient and tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune responses, which may help the participant's body fight any tumor cells that could cause the melanoma to come back in the future. The study will examine the safety of the vaccine when given at several different time points and will examine the participant's blood cells for signs that the vaccine induced an immune response.

Conditions

Melanoma

Keywords

Melanoma; Melanoma vaccine; Adjuvant therapy

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing Clinical and/or Laboratory Dose-limiting Toxicities

  Number of participants experiencing any of the following: * Grade-3 or -4 toxicity that is definitely, probably, or possibly related to the administration of vaccine * Grade-3 or -4 abnormal laboratory value that is definitely, probably, or possibly related to the administration of vaccine if it persists for more than 7 days, requires hospitalization, or medical intervention * Any grade-3 or grade- 4 toxicity that is considered, in the opinion of the investigator, to be dose-limiting * Any death related to study treatment A minimum of 3 vaccinations and absence of DLTs are required for a patient to complete the 7-week DLT observation period successfully.

  7 weeks from first study drug administration

• Proportion of Participants for Whom Sequencing and Analysis Leads to Identification of at Least 10 Actionable Peptides to Initiate Vaccine Production

  The proportion of participants for whom sequencing and analysis leads to identification of at least 10 actionable peptides to initiate vaccine production. The primary assessment of feasibility will be based on on all participants enrolled with a confirmation of completely resected tumor and with adequate DNA and RNA for sequencing. NeoVax would be feasible if no more than 50% of participants have fewer than 10 actionable peptides or have NeoVax available more than 12 weeks after confirmation of complete resection. If 4 or fewer of the first 15 participants have insufficient vaccine or first dose delays of more than 12 weeks, then the upper bound of the one-sided 90% exact confidence interval will be less than 50% and we will consider the process feasible. If 5 or more of the first 15 patients have insufficient or delayed vaccine, we will consider the vaccine not feasible. The planned vaccination regimen will be administered even if the feasibility endpoints are not met.

  12 weeks

Secondary Outcomes (2)

• Proportion of Participants With Specific Cellular Immune Responses Following Administration of NeoVax

  16 weeks

• Proportion of Participants Alive Without Progression at Two Years After Surgery Following Administration of NeoVax

  2 Years

Study Arms (1)

Personalized NeoAntigen Cancer Vaccine

EXPERIMENTAL

\- NeoVax (peptides + poly-ICLC) Poly-ICLC: 4 x 0.5 mg (total dose 2 mg) given on days Days 1, 4, 8, 15, 22, 78, and 134 Peptides: 4 x 300 mcg per peptide given on days Days 1, 4, 8, 15, 22, 78, and 134

Biological: Poly-ICLC; Biological: Peptides

Interventions

Poly-ICLC BIOLOGICAL

Also known as: Hiltonol

Personalized NeoAntigen Cancer Vaccine

Peptides BIOLOGICAL

Also known as: NeoAntigen peptides

Personalized NeoAntigen Cancer Vaccine

Eligibility Criteria

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

You may qualify if:

• Patient is willing and able to give written informed consent.
• Patient is agreeable to allow tumor and normal tissue samples to be submitted for complete exome and transcriptome sequencing.
• Pathologically confirmed, clinically evident (by physical examination or radiographic imaging) stage IIIB, IIIC, IVM1a, or IVM1b cutaneous melanoma (anatomic stages T1-4b N1a and T1-4b N2a not included). The current diagnosis may be the patient's first diagnosis of melanoma or recurrent melanoma after previous diagnosis of an earlier stage melanoma.
• Patients will undergo complete resection of their primary melanoma (if not already removed) and all regional metastatic disease with the intent of rendering them free of melanoma.
• The patient must be free of unresectable metastatic disease within 4 weeks prior to the surgery being performed with the intention to remove all melanoma.
• This pre-surgery baseline assessment must be documented by complete physical examination and imaging studies. Imaging studies must include a total body PET-CT in conjunction with a brain MRI (or head CT if brain MRI is contraindicated). If a PET/CT scan cannot be done, a CT of the neck, chest, abdomen, and pelvis should be performed.
• Patients may have received prior interferon alpha (IFN-α), but must have discontinued IFN-α therapy within 4 weeks prior to enrollment on the trial. Patients who have not received prior adjuvant therapy should be informed of the potential therapeutic benefit of IFN-α.
• Previous radiation therapy, including after the surgical resection, is allowed as long as 14 days have elapsed between the radiation and initiation of first vaccination with NeoVax.
• Age ≥ 18 years.
• ECOG performance status of 0 or 1
• Normal organ and bone marrow function as defined below:
• Leukocytes ≥ 3,500/mcL
• Absolute lymphocyte count \> 800/mcL
• Absolute neutrophil count \> 1,500/mcL
• Platelets \> 100,000/mcL

You may not qualify if:

• Prior treatment with immune-modulatory agents including, but not limited to: IL-2, CTLA-4 blockade, PD-1/PD-L1 blockade, CD40 stimulation, CD137 stimulation with the exception of INF-α given as adjuvant treatment for high-risk, surgically resected melanoma
• Prior investigational, melanoma-directed, cancer vaccine therapy
• Prior chemotherapy, including targeted therapy such as BRAF or MEK inhibition
• Treatment with other investigational products within the last 2 months prior to entry into this study
• Previous bone marrow or stem cell transplant
• Concomitant therapy with any anti-cancer agents, other investigational anti-cancer therapies, or immunosuppressive agents; chronic use of systemic corticosteroids
• Use of a non-oncology vaccine therapy for prevention of infectious diseases (up-to) 4 weeks prior to enrollment to the study. Patients may not receive any non-oncology vaccine therapy during the period of NeoVax 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
• Mucosal melanoma or uveal melanoma are not allowed
• Active, known, or suspected autoimmune disease or immunosuppressive conditions with the exception of vitiligo, type 1 diabetes, residual autoimmune-related hypothyroidism requiring hormone replacement, or psoriasis not requiring systemic treatment.
• Concomitant treatment with corticosteroids greater than physiologic doses (used in the management of cancer or non-cancer-related illnesses). Topical (if not including the proposed vaccination sites) or inhalational steroids are allowed.
• Known chronic infections with HIV, hepatitis B or C
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
• 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.
• Pregnant women are excluded from this study because 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 personalized neoantigen peptides and poly-ICLC, nursing women are excluded from this study.

Sponsors & Collaborators

• Patrick Ott, MD, PhD: lead

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• Srikrishna D, Sachsenmeier K. We need to bring R0 < 1 to treat cancer too. Genome Med. 2021 Jul 26;13(1):120. doi: 10.1186/s13073-021-00940-9.

  PMID: 34311780 DERIVED

• Hu Z, Leet DE, Allesoe RL, Oliveira G, Li S, Luoma AM, Liu J, Forman J, Huang T, Iorgulescu JB, Holden R, Sarkizova S, Gohil SH, Redd RA, Sun J, Elagina L, Giobbie-Hurder A, Zhang W, Peter L, Ciantra Z, Rodig S, Olive O, Shetty K, Pyrdol J, Uduman M, Lee PC, Bachireddy P, Buchbinder EI, Yoon CH, Neuberg D, Pentelute BL, Hacohen N, Livak KJ, Shukla SA, Olsen LR, Barouch DH, Wucherpfennig KW, Fritsch EF, Keskin DB, Wu CJ, Ott PA. Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma. Nat Med. 2021 Mar;27(3):515-525. doi: 10.1038/s41591-020-01206-4. Epub 2021 Jan 21.

  PMID: 33479501 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

poly ICLC; Peptides

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)

Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Patrick Ott, MD PhD
• Organization: Dana-Farber Cancer Institute

patrick_ott@dfci.harvard.edu

6176325990

Study Officials

• Patrick Ott, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 9, 2013
• First Posted: October 28, 2013
• Study Start: April 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: June 1, 2018
• Last Updated: December 29, 2025
• Results First Posted: December 29, 2025

Record last verified: 2025-12

Locations

US (2)