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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04160065
Recruitment Status : Recruiting
First Posted : November 12, 2019
Last Update Posted : March 26, 2020
Sponsor:
Collaborators:
H. Lee Moffitt Cancer Center and Research Institute
University of Southern California
Information provided by (Responsible Party):
Morphogenesis, Inc.

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

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
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 : July 2021
Estimated Study Completion Date : September 2021


Arm Intervention/treatment
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.
Biological: IFx-Hu2.0

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).
  • 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).
  • 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).

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).
Other Name: pAc/emm55




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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04160065


Contacts
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Contact: Michael JP Lawman, PhD 813-875-6600 ext 101 mlawman@morphogenesis-inc.com
Contact: Patricia D Lawman, PhD 813-875-6600 ext 102 plawman@morphogenesis-inc.com

Locations
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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   
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   
Principal Investigator: Andrew S Brohl, MD         
Sponsors and Collaborators
Morphogenesis, Inc.
H. Lee Moffitt Cancer Center and Research Institute
University of Southern California
Investigators
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Principal Investigator: Andrew S Brohl, MD Collaborator

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Responsible Party: Morphogenesis, Inc.
ClinicalTrials.gov Identifier: NCT04160065    
Other Study ID Numbers: NMSC 2019-01
First Posted: November 12, 2019    Key Record Dates
Last Update Posted: March 26, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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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
Vaccines
Immunologic Factors
Physiological Effects of Drugs