Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

pDNA Intralesional Cancer Vaccine for Cutaneous 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. Read our disclaimer for details. Identifier: NCT03655756
Recruitment Status : Completed
First Posted : August 31, 2018
Results First Posted : August 8, 2022
Last Update Posted : August 8, 2022
H. Lee Moffitt Cancer Center and Research Institute
Information provided by (Responsible Party):
Morphogenesis, Inc.

Brief Summary:
Six patients will receive IFx-Hu2.0 on an outpatient basis at a single time point in a single lesion, two lesions, or three lesions, as a monotherapy (a maximum of three lesions could be injected). These patients will be assessed for any immediate adverse reactions and at Week 4 (Day 28+/-7 business days for any delayed adverse events.

Condition or disease Intervention/treatment Phase
Cutaneous Melanoma, Stage III Cutaneous Melanoma, Stage IV Biological: IFx-Hu2.0 Early Phase 1

Detailed Description:

Six male and/or female adult patients (greater than or equal to 18 years old), of any ethnicity and race, with unresectable stage III or stage IV cutaneous melanoma with accessible lesions, will be eligible for enrollment and treatment with IFx-Hu2.0.

To be eligible for this study, patients with unresectable metastatic disease must have failed, refused or been deemed not candidates for at least one form of systemic anti-PD-1-based immunotherapy as well as BRAF inhibition, if BRAF V600 mutated. Talimogene laherparepvec (IMLYGIC®) is indicated for local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Therefore, patients with unresectable cutaneous, subcutaneous, and nodal melanoma lesions recurrent after initial surgery must have failed, refused or been deemed not candidates for talimogene laherparepvec to be eligible for this study.

Enrollees will receive IFx-Hu2.0 at a single time point. Depending on the number of accessible lesions, a patient could receive up to three doses across three lesions (one dose per lesion). Forty milliliters of peripheral blood will be collected from these patients prior to treatment administration and at the follow-up visit four weeks later. The target dose will be 100 μg of plasmid DNA per lesion injected at a final dose volume of 200 μL per lesion. To allow for the observation of any acute toxicity in the first subject enrolled and prevent any occurrence of excessive toxicities in subsequent subjects, the first subject enrolled will receive a single dose of IFx-Hu2.0. Subsequent subjects will be administered the product after at least seven days. Beyond the first subject, the maximum number of lesions to be injected at any given time point in the study phase proposed is three lesions. These samples will be used to perform complete blood counts (CBC) and clinical chemistry tests. A urine sample will be obtained for urinalysis for protein and blood at the same frequency. Blood samples will be drawn for immune response evaluation as well. At the end of the study period, a biopsy of the lesion injected and a non-injected lesion (if applicable) will be collected. If the patient has a response to therapy, the patient will have the option of continuing the study at three-week intervals so long as they have not progressed. Optional tumor biopsies and peripheral blood collections may be obtained on subsequent treatment cycles.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study Using a Plasmid DNA Coding for Emm55 Streptococcal Antigen in Patients With Unresectable Stage III or Stage IV Cutaneous Melanoma
Actual Study Start Date : November 5, 2018
Actual Primary Completion Date : July 10, 2020
Actual Study Completion Date : November 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: IFx-Hu2.0 (plasmid DNA) 0.1 mg/lesion/time point

Therapeutic Classification:

  • Noncellular, Therapeutic Cancer Vaccine > Immunomodulator

Route of Administration:

  • Intratumoral injection of cutaneous, subcutaneous or nodal lesions

Mechanism of Action:

  • Injection of the IFx-Hu2.0 plasmid DNA construct into the target lesion facilitates the localized expression of the highly immunogenic Emm55 protein by the tumor cells on their cell surface.

Physiological Effect:

  • This expression then primes a cascade of immune events that exposes the patient-specific abnormal tumor antigens to the effector mechanisms of the immune system. The immune response becomes systemic as inter-antigenic epitope spreading produces neoantigens to naïve T cells. Therefore, injected lesions are targeted along with non-injected lesions (abscopal effect). This is especially important in conditions where the mutational phenotype varies greatly among individual lesions.
Biological: IFx-Hu2.0
Subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at a single time point (28-day follow-up post last injection).
Other Name: pAc/emm55

Primary Outcome Measures :
  1. Number of Participants With Serious Adverse Events (SAEs) and/or Dose Limiting Toxicities (DLTs) [ Time Frame: 28 ± 7 Days ]
    Safety was reported using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Feasibility was defined as the ability to treat at least five of the six patients enrolled without drug-related dose-limiting toxicity (DLT).

Secondary Outcome Measures :
  1. Antitumor Response Induced by IFx-Hu2.0 Per RECIST v1.1 for Target Lesions. [ Time Frame: 28 ± 7 days post treatment ]

    Evaluation of response rate and assessment of the antitumor immune responses induced by IFx-Hu2.0 per RECIST v1.1 for target lesions.

    Complete Response (CR), Disappearance of all target lesions. Partial Response (PR), ≥ 30% decrease in the sum of the longest diameters of target lesions compared with baseline.

    Stable Disease (SD), Neither sufficient shrinkage to qualify for partial or complete response (CR or PR) nor sufficient increase to qualify for progressive disease (PD).

    Progressive Disease (PD), Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed unresectable stage III or stage IV malignant melanoma, with accessible cutaneous lesions
  • Must have measurable disease greater than 3 mm
  • At least one injectable lesion and one lesion for biopsy at study conclusion. Lymphocyte count ≥ 500,000 cells/mL
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Willing and able to give written, informed consent
  • If male or female of childbearing potential must be willing to use a contraceptive during the study and for six months afterward. A woman is considered to be of childbearing potential unless she has had a surgical procedure that would accomplish sterility such a bilateral tubal ligation, hysterectomy or has not had menses for the past 12 months.
  • Life expectancy greater than three months
  • To be eligible for this study, patients with unresectable metastatic disease must have failed, refused or been deemed not candidates for at least one form of systemic anti-PD-1-based immunotherapy as well as BRAF inhibition, if BRAF V600 mutated.
  • Patients with unresectable cutaneous, subcutaneous, and nodal melanoma lesions recurrent after initial surgery must have failed, refused or been deemed not candidates for talimogene laherparepvec to be eligible for this study.
  • The entry laboratory criteria for subject eligibility must be less than or equal to grade 1 adverse event levels for the parameters tested as defined by CTCAE v5.0.

Exclusion Criteria:

  • Known brain metastases greater than 1 cm at screening.
  • Life expectancy of fewer than three months
  • Prior systemic anti-cancer treatment within three weeks from start of treatment (Day 0)
  • Current treatment with systemic immunosuppressive corticosteroid (greater than 10 mg of daily prednisone) doses or other immunosuppressants such as those needed for solid organ transplants. Medications needed to treat conditions such as reactive airway disease are not excluded.
  • Pregnant or lactating women
  • Presence of any uncontrolled and significant medical or psychiatric condition which would interfere with trial safety assessments
  • Treatment with any investigational product within the three weeks preceding injection
  • Immunizations for encapsulated bacteria were not given for patients who have undergone a splenectomy.
  • Serious underlying medical or psychiatric conditions, active infections requiring the use of antimicrobial drugs, or active bleeding that would make the subject unsuitable or unable to participate in the study
  • Concurrent chemotherapy or biological therapy. Concurrent radiotherapy is allowed as long as it is not the same site as the injected lesion.
  • Uncontrolled hepatitis B, hepatitis C, or HIV infection
  • History of organ allograft transplantation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03655756

Layout table for location information
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
Sponsors and Collaborators
Morphogenesis, Inc.
H. Lee Moffitt Cancer Center and Research Institute
Layout table for investigator information
Principal Investigator: Joseph Markowitz, MD, PhD Collaborator
  Study Documents (Full-Text)

Documents provided by Morphogenesis, Inc.:
Informed Consent Form  [PDF] April 21, 2019

Layout table for additonal information
Responsible Party: Morphogenesis, Inc. Identifier: NCT03655756    
Other Study ID Numbers: CM 2017-01
First Posted: August 31, 2018    Key Record Dates
Results First Posted: August 8, 2022
Last Update Posted: August 8, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Morphogenesis, Inc.:
Plasmid DNA
Gene Therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms by Site
Skin Diseases