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.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma	Biological: IFx-Hu2.0	Phase 1

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 3, 2020
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: June 2022

Arms and Interventions

Arm

Intervention/treatment

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.

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

Outcome Measures

Primary Outcome Measures :

1. Number of Grade 3-5, Treatment-Related Adverse Events per CTCAE 5.0 [ Time Frame: 28 days from last injection ]

Secondary Outcome Measures :

1. Number of Enrolled Subjects who have completed the Trial without Major Protocol Deviations [ Time Frame: 28 days from last injection ]
2. 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 ]
3. Best Overall Response per RECIST v1.1 [ Time Frame: 28 days from last injection ]

Eligibility Criteria

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

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

Contacts and Locations

Contacts

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

Locations

United States, California

USC Norris Comprehensive Cancer Center; Recruiting

Los Angeles, California, United States, 90033

Contact: Jacob S Thomas, MD 323-865-0451 jacob.thomas@med.usc.edu

Contact: Rabia Rehman 323-865-0460 rabia.rehman@med.usc.edu

Principal Investigator: Jacob S Thomas, MD

United States, Florida

H. Lee Moffitt Cancer Center and Research Institute; Recruiting

Tampa, Florida, United States, 33612

Contact: Andrew S Brohl, MD 813-745-4673 andrew.brohl@moffitt.org

Contact: Deanryan De'Aquino 813-745-3998 deanryan.deaquino@moffitt.org

Principal Investigator: Andrew S Brohl, MD

United States, Massachusetts

Dana-Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Ann W Silk, MD 617-632-3000 ann_silk@dfci.harvard.edu

Contact: Andrea Saric-Hayes 617-582-7979 andrea_saric-hayes@dfci.harvard.edu

Principal Investigator: Ann W Silk, MD

United States, Utah

Huntsman Cancer Institute; Recruiting

Salt Lake City, Utah, United States, 84112

Contact: John R Hyngstrom, MD 801-587-7000 john.hyngstrom@hci.utah.edu

Contact: Susan Sharry 801-585-3453 susan.sharry@hci.utah.edu

Principal Investigator: John R Hyngstrom, MD

Sponsors and Collaborators

Morphogenesis, Inc.

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

More Information

• Responsible Party: Morphogenesis, Inc.
• ClinicalTrials.gov Identifier: NCT04160065
• Other Study ID Numbers: NMSC 2019-01
• First Posted: November 12, 2019
• Last Update Posted: July 13, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Morphogenesis, Inc.:

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

Additional relevant MeSH terms:

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