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pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma

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ClinicalTrials.gov Identifier: NCT03655756
Recruitment Status : Completed
First Posted : August 31, 2018
Last Update Posted : February 23, 2021
Sponsor:
Collaborator:
H. Lee Moffitt Cancer Center and Research Institute
Information provided by (Responsible Party):
Morphogenesis, Inc.

Tracking Information
First Submitted Date  ICMJE August 23, 2018
First Posted Date  ICMJE August 31, 2018
Last Update Posted Date February 23, 2021
Actual Study Start Date  ICMJE November 5, 2018
Actual Primary Completion Date July 10, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2018)
  • Safety; defined as four of the six patients enrolled having no grade-3 or higher treatment-related adverse events as assessed by CTCAE v5.0. [ Time Frame: 28 Days ]
  • Feasibility; defined as the ability to treat at least five of the six patients enrolled without dose-limiting toxicity. [ Time Frame: 28 Days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2018)
Objective response rate (ORR) determined using standard criteria. [ Time Frame: 1 Year ]
ORR is defined as the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. Response duration usually is measured from the time of initial response until documented tumor progression.
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 pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma
Official Title  ICMJE Phase 1 Study Using a Plasmid DNA Coding for Emm55 Streptococcal Antigen in Patients With Unresectable Stage III or Stage IV Cutaneous Melanoma
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cutaneous Melanoma, Stage III
  • Cutaneous Melanoma, Stage IV
Intervention  ICMJE 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
Study Arms  ICMJE 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.
Intervention: Biological: IFx-Hu2.0
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 29, 2018)
6
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 4, 2020
Actual Primary Completion Date July 10, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03655756
Other Study ID Numbers  ICMJE CM 2017-01
Has Data Monitoring Committee Not Provided
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: No
Responsible Party Morphogenesis, Inc.
Study Sponsor  ICMJE Morphogenesis, Inc.
Collaborators  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Investigators  ICMJE
Principal Investigator: Joseph Markowitz, MD, PhD Collaborator
PRS Account Morphogenesis, Inc.
Verification Date February 2021

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