Clinical Trials /

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

NCT04160065

Description:

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).

Related Conditions:
  • Merkel Cell Carcinoma
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: NMSC 2019-01
  • NCT ID: NCT04160065

Conditions

  • Merkel Cell Carcinoma
  • Cutaneous Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
IFx-Hu2.0pAc/emm55IFx-Hu2.0 (plasmid DNA) 0.1 mg/lesion/time point

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
IFx-Hu2.0 (plasmid DNA) 0.1 mg/lesion/time pointExperimentalTherapeutic 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.
  • IFx-Hu2.0

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Grade 3-5, Treatment-Related Adverse Events per CTCAE 5.0
Time Frame:28 days from last injection
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Morphogenesis, Inc.

Trial Keywords

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

Last Updated