Immunotherapy With IFx-Hu2.0 Vaccine for Advanced MCC or cSCC

• ClinicalTrials.gov Identifier: NCT04160065
• Recruitment Status: Recruiting
• First Posted: November 12, 2019
• Last Update Posted: July 13, 2021
• Sponsor: Morphogenesis, Inc.
• Collaborators: H. Lee Moffitt Cancer Center and Research Institute; University of Southern California; Dana-Farber Cancer Institute; Huntsman Cancer Institute
• Information provided by (Responsible Party): Morphogenesis, Inc.

Tracking Information

• First Submitted Date: November 7, 2019
• First Posted Date: November 12, 2019
• Last Update Posted Date: July 13, 2021
• Actual Study Start Date: March 3, 2020
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 8, 2019): Number of Grade 3-5, Treatment-Related Adverse Events per CTCAE 5.0 [ Time Frame: 28 days from last injection ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 8, 2019)

• Number of Enrolled Subjects who have completed the Trial without Major Protocol Deviations [ Time Frame: 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 [ Time Frame: 28 days from last injection ]
• Best Overall Response per RECIST v1.1 [ Time Frame: 28 days from last injection ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Immunotherapy With IFx-Hu2.0 Vaccine for Advanced MCC or cSCC
• Official Title: Phase 1 Trial of Intralesional Immunotherapy With IFx-Hu2.0 Vaccine in Patients With Advanced Merkel Cell Carcinoma or Cutaneous Squamous Cell Carcinoma
• 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 Merkel cell carcinoma (MCC) or cutaneous squamous cell carcinoma (cSCC) 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).

Detailed Description

Approximately twenty adult patients (≥ 18 years of age), of any sex, ethnicity, and race with histologically confirmed MCC or cSCC with accessible lesions, will be eligible for study enrollment and treatment with IFx-Hu2.0 (i.e. 20 total patients across both indications). These types of non-melanoma cancers are very rare in the pediatric population (< 18 years of age) with only scattered case reports. The potential for development of this product for pediatric subjects with MCC or cSCC will be evaluated after the results of this study are available.

Patients must have at least one injectable lesion, 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.

To be eligible for this study, patients must have progressed despite standard therapy(ies), or are intolerant to or refused standard therapy(ies).

Enrollees will receive IFx-Hu2.0 as a monotherapy at up to three time points. Depending on the number of accessible lesions, a patient could receive up to three doses across three lesions (one dose per lesion). The maximum number of lesions to be injected at any time point under this protocol is three lesions. Blood will be collected from these patients prior to treatment administration at every drug administration visit. These samples will be used to perform CBC and clinical chemistry tests. A urine sample will be obtained for urinalysis for protein and blood at the same frequency. Blood samples will also be drawn at the same intervals for immune response evaluation as well.

This is primarily a safety study that is designed to evaluate IFx-Hu2.0 monotherapy and provide foundational evidence to potentially support further studies investigating IFx-Hu2.0 + anti-PD-1 combination therapy for patients with advanced MCC or cSCC.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Merkel Cell Carcinoma
• Cutaneous Squamous Cell Carcinoma

Intervention

Biological: IFx-Hu2.0

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.

Other Name: pAc/emm55

Study Arms

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

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.

Intervention: Biological: IFx-Hu2.0

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 8, 2019): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2022
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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 Merkel cell carcinoma (MCC) or cutaneous squamous cell carcinoma (cSCC)
• 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

  • Hepatic Function:

    • Blood bilirubin < 1 - 1.5 x ULN if baseline was normal; < 1 1.5 x baseline if baseline was abnormal
    • Serum Alanine Aminotransferase (ALT) < 1 - 3 x ULN if baseline was normal; 1.5 3 x baseline if baseline was abnormal
    • Serum Aspartate Aminotransferase (AST) < 1 - 3 x ULN if baseline was normal; 1.5 3 x baseline if baseline was abnormal
    • Alkaline Phosphatase (ALP) < 1 - 2.5 x ULN if baseline was normal; 2 2.5 x baseline if baseline was abnormal
    • Gamma Glutylamyltransferase (GGT) < 1 - 2.5 x ULN, if baseline was normal; 2 2.5 x baseline if baseline was abnormal
• Males and females of reproductive potential must agree to continuously use adequate contraception prior to study entry and for up to 6 months thereafter. A female is 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.
• Females of childbearing potential must have a negative urine or serum pregnancy test within one week prior to start of treatment
• Patient or legal representative must understand and sign a written informed consent form.

Exclusion Criteria:

• 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.
• History of autoimmune disorder, with exception of patients with vitiligo or endocrine-related autoimmune conditions receiving appropriate hormonal supplementation who are eligible; systemic use of immunosuppressant drugs such as steroids (except as hormone replacement therapy or short-course supportive medication such as chemotherapy or drug allergy, etc.), azathioprine, tacrolimus, cyclosporine, etc. within 4 weeks before recruitment
• 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 infections or other 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: James A Bianco, MD; (813) 875-6600 ext 104; jbianco@morphogenesis-inc.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04160065
• Other Study ID Numbers: NMSC 2019-01
• 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

• Plan to Share IPD: No

• Responsible Party: Morphogenesis, Inc.
• Study Sponsor: Morphogenesis, Inc.

Collaborators

• H. Lee Moffitt Cancer Center and Research Institute
• University of Southern California
• Dana-Farber Cancer Institute
• Huntsman Cancer Institute

Investigators

• Principal Investigator: Andrew S Brohl, MD; Collaborator

• PRS Account: Morphogenesis, Inc.
• Verification Date: July 2021