Immunotherapy With IFx-Hu2.0 Vaccine for Advanced Non-melanoma Skin Cancers

NCT04160065 | Completed Phase 1 FDA Drug

• 1 other identifier: NMSC 2019-01
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

Brief Summary

In this clinical phase I, non-randomized, open-label, uncontrolled, interventional, multi-center trial, 20 adult subjects (≥ 18 years of age) with advanced non-melanoma skin cancers will receive a fixed dose of 0.1 mg of IFx-Hu2.0 intralesionally as monotherapy in up to three lesions at up to three time points. Subjects will be observed for any acute adverse events (AEs) post injection and for any delayed AEs at Day 28, 35 and/or 42 ± 7 days, depending on the cohort (exposure escalation and expansion design).

Conditions

Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma; Non-Melanoma Skin Cancers

Keywords

Advanced; MCC; cSCC; pDNA; plasmid DNA; pAc/emm55; Gene Therapy; Immuno-Oncology; Therapeutic Cancer Vaccine; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Grade 3-5, Treatment-Related Adverse Events per CTCAE 5.0

  28 days from last injection

Secondary Outcomes (3)

• Number of Enrolled Subjects who have completed the Trial without Major Protocol Deviations

  28 days from last injection

• Objective Response Rate (ORR) per 2018 FDA Guidance on Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics

  28 days from last injection

• Best Overall Response per RECIST v1.1

  28 days from last injection

Study Arms (1)

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

EXPERIMENTAL

Exposure Escalation: * The first 3 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); 3/3 patients recruited. * The second 3 subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at 2 time points 7 days apart (28-day follow-up post last injection); 1/3 patients recruited. * The third 3 subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at 3 time points 7 days apart (28-day follow-up post last injection); recruitment pending. Cohort Expansion: * The remaining 11 subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at 3 time points 7 days apart (28-day follow-up post last injection); recruitment pending.

Biological: IFx-Hu2.0

Interventions

IFx-Hu2.0 BIOLOGICAL

The investigational drug product IFx-Hu2.0 is composed of the drug substance pAc/emm55 (pDNA) complexed with the two excipients in vivo-jetPEI® (linear polyethylenimine), a transfection reagent, and dextrose, a pDNA/polyethylenimine complex stabilizer. Therapeutic Classification: * Immunomodulatory Agent Route of Administration: * Intralesional (i.e. injection of cutaneous, subcutaneous or nodal lesions) Mechanism of Action: * Injection of IFx-Hu2.0 into the lesion facilitates the expression of the immunogenic Emm55 protein by the tumor cells. Physiological Effect: * Expression of the emm55 gene by the tumor cells triggers immune recognition of tumor-specific and -associated antigens which leads to innate and adaptive immune responses.

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:

• Life expectancy ≥ 3 months at recruitment
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at the time of study treatment initiation.
• Males or females with histologically confirmed diagnosis of advanced non-melanoma skin cancers.
• Patients must have progressed despite standard therapy(ies) or are intolerant to or refused standard therapy(ies).
• Clinically measurable disease with at least 1 injectable lesion ≥ 3 mm in longest diameter; an injectable lesion is defined as an easily palpable superficial lesion (cutaneous, subcutaneous or lymph nodal metastasis) that can be accurately localized, stabilized by palpation, and is superficial enough to enable intralesional injection.
• No known bleeding diathesis or coagulopathy that would make intratumoral injection or biopsy unsafe
• 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:
• Bone Marrow Function:
• Hemoglobin (Hb) \> LLN 10 g/dL
• White Blood Cell Count (WBC) \> LLN 3,000 cells/mcL
• Platelet count (PLT) \> LLN - 75,000 /mcL
• Blood Coagulation Parameters
• PT, INR \< 1.5 x institutional ULN unless patient is therapeutically anticoagulated. If on anticoagulation PT/INR need to be within appropriate anticoagulation limits for the clinical indication. Patients who are receiving anticoagulants may participate in the trial if their anticoagulation can be stopped safely for several days at the time of biopsy.
• Renal Function
• Serum Creatinine (SCr) \< 1 - 1.5 x baseline; \< 1 1.5 x ULN

You may not qualify if:

• Concurrent use of any other investigational product or participation in another trial within 28 days before start of study treatment.
• Have received oncologic therapy within 2 weeks of planned IFx-Hu2.0 injection
• Presence or history of central nervous system metastasis \[treated/stable brain metastasis are allowable when patients have received prior therapy for their brain metastases and their central nervous system (CNS) disease is radiographically stable (\> 4 weeks)\]
• Pregnant or breastfeeding females and females desiring to become pregnant or breastfeed within the timeframe of this study
• Concurrent steroid therapy (\> 10 mg of daily prednisone equivalent) or other immunosuppressive therapies such as those needed for solid organ transplants and rheumatoid arthritis. Topical or inhaled steroids are allowable.
• History of organ allograft transplantation
• History of hemolytic anemia
• History of significant tumor bleeding, or coagulation or bleeding disorders.
• Major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery
• Leptomeningeal involvement regardless of treatment status
• Active, clinically serious uncontrolled medical conditions such as HIV, HBV, HCV, and EBV infection
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with protocol requirements
• Unwilling or unable to follow protocol requirements

Sponsors & Collaborators

• TuHURA Biosciences, Inc.: lead
• H. Lee Moffitt Cancer Center and Research Institute: collaborator
• University of Southern California: collaborator
• Dana-Farber Cancer Institute: collaborator
• Huntsman Cancer Institute: collaborator

Study Sites (4)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Andrew S Brohl, MD

  Collaborator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 12, 2019
• Study Start: March 3, 2020
• Primary Completion: October 19, 2023
• Study Completion: August 13, 2024
• Last Updated: September 23, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)