pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma

NCT03655756 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: CM 2017-01
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Cutaneous Melanoma, Stage III; Cutaneous Melanoma, Stage IV

Keywords

Unresectable; Melanoma; pDNA; Plasmid DNA; Gene Therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Serious Adverse Events (SAEs) and/or Dose Limiting Toxicities (DLTs)

  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).

  28 ± 7 Days

Secondary Outcomes (1)

• Antitumor Response Induced by IFx-Hu2.0 Per RECIST v1.1 for Target Lesions.

  28 ± 7 days post treatment

Study Arms (1)

IFx-Hu2.0 (plasmid DNA) 0.1 mg/lesion/time point

EXPERIMENTAL

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

Interventions

IFx-Hu2.0 BIOLOGICAL

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).

Also known as: pAc/emm55

IFx-Hu2.0 (plasmid DNA) 0.1 mg/lesion/time point

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• TuHURA Biosciences, Inc.: lead
• H. Lee Moffitt Cancer Center and Research Institute: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Melanoma

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

Results Point of Contact

• Title: James Bianco, MD - Chief Executive Officer
• Organization: Morphogenesis, Inc

jbianco@morphogenesis-inc.com

8138756600

Study Officials

• Joseph Markowitz, MD, PhD

  Collaborator

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: August 31, 2018
• Study Start: November 5, 2018
• Primary Completion: July 10, 2020
• Study Completion: November 30, 2020
• Last Updated: August 8, 2022
• Results First Posted: August 8, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)