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NeoVax + CDX-301 and Nivolumab in Advanced Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04930783
Recruitment Status : Not yet recruiting
First Posted : June 18, 2021
Last Update Posted : June 18, 2021
Celldex Therapeutics
Information provided by (Responsible Party):
Patrick Ott, MD, Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE June 11, 2021
First Posted Date  ICMJE June 18, 2021
Last Update Posted Date June 18, 2021
Estimated Study Start Date  ICMJE November 2021
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 11, 2021)
  • Rate of Dose Limiting Toxicity (DLT) [ Time Frame: Toxicities experienced within 49 days/7 weeks of Neoantigen Vaccine treatment initiation ]
    Based on the CTEP Active Version (version 5.0) of the NCI Common Terminology Criteria for Adverse Events (CTCAE).
  • Recommended maximum tolerated dose (MTD) [ Time Frame: Up to 12 weeks for each dosing cohort ]
    Highest dose of CDX-301 that did not cause a dose limiting toxicity
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2021)
  • Neoantigen-specific cellular immune responses [ Time Frame: Enrollment to end of treatment up to 24 weeks ]
    Evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
  • Anti-tumor activity at Week 24 [ Time Frame: Week 24 ]
    Evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
  • Response conversion rate (RCR) at Week 24 [ Time Frame: Week 24 ]
    Evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE NeoVax + CDX-301 and Nivolumab in Advanced Melanoma
Official Title  ICMJE A Phase Ib Study of NeoVax in Combination With CDX-301 and Nivolumab and in Patients With Advanced Melanoma
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 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)
Detailed Description

The purpose of this Phase I study is to determine if it is possible to safely administer a personalized neoantigen vaccine (NeoVax) in combination with the study drug CDX-301 and Nivolumab against melanoma by using information gained from specific characteristics of someone's own melanoma. The study will also be determining what the appropriate dose of CDX-301 to be given in combination with NeoVax and Nivolumab.

The FDA (the U.S. Food and Drug Administration) has not approved personalized neoantigen peptides, poly-ICLC , or CDX-301 as a treatment for any disease.

The FDA has approved Nivolumab as a treatment option for metastatic melanoma.

It is known that melanoma cancers 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 someone's body fight any tumor cells that could cause the melanoma to come back in the future.

The personalized Neovax vaccine will be made of protein fragments, called peptides, from an individual's mutated melanoma tumor cells mixed with Poly-ICLC. Poly-ICLC is a drug that binds proteins on the surface of certain immune cells and helps to activate the immune system.

CDX-301 is a drug involved in regulating the activity and proliferation of a type of cell named dendritic cell. Dendritic cells are key in enhancing the activation of the immune system in response to the NeoVax vaccine, so the immune system has a better chance to recognize the tumor cells and attack them.

Nivolumab is an antibody that prevents cancer cells from suppressing one's immune response so that their body can attack and kill the cancer.

The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits.

Participants will receive study treatment for as long as they do not have serious side effects and their disease does not get worse for a maximum of 2 years and will be followed for 5 years since study therapy initiation

It is expected that about 20 people will take part in this research study

Celldex Therapeutics is supporting this research by providing CDX-301.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Melanoma
  • Metastatic Melanoma
Intervention  ICMJE
  • Drug: CDX-301
    Administered as an injection given underneath the skin
  • Biological: NEOVAX
    Personalized neoantigen vaccine administered as an injection given underneath the skin
  • Drug: Nivolumab
    Administered intravenously (IV)
    Other Name: Opdivo
Study Arms  ICMJE Experimental: CDX-301 + Neovax + Nivolumab
  • Participants will undergo metastatic tumor biopsy with vaccine made from collected 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 11, 2021)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2027
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Eligibility to participate will be assessed at two timepoints: prior to initial core needle/surgical biopsy (Initial Registration) and prior to the first vaccination (Secondary Registration).

  • Eligibility Criteria for Initial Registration

    • Participant is willing and able to give written informed consent
    • Participants must have histologically confirmed cutaneous melanoma (mucosal melanoma or uveal melanoma are excluded) 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 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
    • Recovered from all toxicities associated with prior treatment, to acceptable baseline status (as to Lab toxicity see below limits for inclusion) or a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0, Grade of 0 or 1, except for toxicities not considered a safety risk, such as alopecia or vitiligo
    • 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

Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL

  • Women of childbearing potential (WOCBP) should have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Nivolumab, because the effects of NeoVax plus Montanide and Nivolumab on the developing human fetus are unknown
  • Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study agents, breastfeeding should be discontinued if the mother is treated Nivolumab, Personalized Neoantigen vaccine, and CDX-301
  • Female participants enrolled in the study, who are not free from menses for >2 years, post hysterectomy / oophorectomy, or surgically sterilized, should be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from sexual activity throughout the study, starting with visit 1 through 5 months after the last dose of study therapy. Approved contraceptive methods include for example: intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.The investigational product will be permanently discontinued in an appropriate manner.
  • Male participants should agree to use an adequate method of contraception starting with visit 1 through 7 months after the last dose of study therapy

Exclusion Criteria:

  • Prior immunotherapy for metastatic melanoma except anti-CTLA-4. Patients 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 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
  • Has received a live vaccine within 30 days of planned start of study therapy. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine.

Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

  • 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 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
  • Patients with known mutations/amplifications in Flt-3
  • 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
  • Prisoners, or subjects who are compulsory detained are not eligible to participate
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Patrick A Ott, MD, PhD (617) 632-5055
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT04930783
Other Study ID Numbers  ICMJE 21-066
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (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
Responsible Party Patrick Ott, MD, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE Celldex Therapeutics
Investigators  ICMJE
Principal Investigator: Patrick A Ott, MD, PhD Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP