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MG1-MAGEA3 With Ad-MAGEA3 and Pembrolizumab in Patients With Previously Treated Metastatic Melanoma or Cutaneous Squamous Cell Carcinoma (Pelican)

Primary Purpose

Metastatic Melanoma, Squamous Cell Skin Carcinoma

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Ad-MAGEA3
MG1-MAGEA3
Pembrolizumab
Cyclophosphamide
Sponsored by
Turnstone Biologics, Corp.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Have histologically or cytologically confirmed diagnosis of locally advanced metastatic melanoma or cutaneous squamous cell carcinoma that has failed standard therapies
  • For patients treated intratumorally, must have a lesion suitable for direct injection of MG1-MAGEA3
  • Have at least one tumor amenable to biopsy
  • Have measurable disease via RECIST 1.1 criteria
  • Adequate organ function and performance status
  • Additional inclusion criteria present

Exclusion Criteria:

  • Prior treatment with any MAGE-A3 vaccine immunotherapy
  • Prior systemic therapy for cancer within 4 weeks (8 weeks for lung radiation), and has recovered from chemo-related toxicities to Grade 1 or less
  • Intolerant to prior PD1/PD-L1 therapy
  • Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies or intra-tumoral injections.
  • Known active CNS metastases and/or carcinomatous meningitis.
  • Active autoimmune disease that has required systemic therapy in the past 2 years.
  • Conditions likely to have resulted in splenic dysfunction.
  • Known HIV/AIDS, active HBV or HCV infection.
  • Additional Exclusion criteria exist

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Arm 1: Intravenous Dosing

    Arm 2: Intravenous followed by Intratumoral Dosing

    Arm Description

    Low dose cyclophosphamide (300mg/ m2) at Day -3, then a fixed dose of Ad-MAGEA3 administered IM on study Day 1. Followed by one of 3 dose levels (escalation) of MG1-MAGEA3 administered as 2 intravenous (IV) doses at Day 15 and Day 18 and fixed dose pembrolizumab (200mg) beginning at either Week 6 or Day 1, depending on the cohort.

    A fixed dose of Ad-MAGEA3 administered IM followed by Pembrolizumab on Day 1. MG1-MAGEA3 administered as an intravenous (IV) dose at Day 15, followed by intratumoral (IT) MG1-MAGEA3 on Day 22, Day 29, and Day 36. IT MG1-MAGEA3 booster injections may be continued every 3 weeks beginning at Day 43 (Week 6).

    Outcomes

    Primary Outcome Measures

    Safety of Ad/MG1-MAGEA3 administration in Melanoma or Squamous Cell Skin Carcinoma
    Safety will be determined by assessing the severity and frequency of treatment emergent Adverse Events and clinical laboratory toxicity using NCI CTCAE v 5.0
    Determine the maximum tolerated dose (MTD)/ maximum feasible dose (MFD) of Ad/MG1-MAGEA3 in Melanoma or Squamous Cell Skin Carcinoma
    MTD/MFD of Ad/MG1-MAGEA3 administered by IV infusion alone and IV infusion followed by direct injection of tumor (IT injection) in Melanoma or Squamous Cell Skin Carcinoma

    Secondary Outcome Measures

    Evaluate Overall Response
    Determine the overall response rate (Partial Response (PR) + Complete Response (CR))
    Evaluate Disease Control
    Determine Disease Control Rate (PR+CR+Stable Disease (SD))
    Evaluate PFS
    Progression free survival in months
    Evaluate Duration of Response, if any
    Duration of Response (CR, PR, SD) in months

    Full Information

    First Posted
    December 10, 2018
    Last Updated
    April 1, 2021
    Sponsor
    Turnstone Biologics, Corp.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03773744
    Brief Title
    MG1-MAGEA3 With Ad-MAGEA3 and Pembrolizumab in Patients With Previously Treated Metastatic Melanoma or Cutaneous Squamous Cell Carcinoma
    Acronym
    Pelican
    Official Title
    A Phase 1b, Multicenter, Open-label Trial of Oncolytic MG1 Expressing MAGE-A3 (MG1-MAGEA3) With Adenovirus Vaccine Expressing MAGE-A3 (Ad-MAGEA3), in Combination With Immune Modulating Therapy in Patients With Metastatic Melanoma or Previously Treated Cutaneous Squamous Cell Carcinoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2021
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    insufficient suitable drug supply
    Study Start Date
    February 15, 2020 (Actual)
    Primary Completion Date
    October 30, 2020 (Anticipated)
    Study Completion Date
    December 31, 2021 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Turnstone Biologics, Corp.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is a Phase 1b open-label dose escalation trial of Ad/MG1-MAGEA3 and Pembrolizumab in patients with Metastatic Melanoma or Cutaneous Squamous Cell Skin Cancer that has failed prior standard of care treatments. Upon determination of a Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD) the study will be expanded into up to 24 additional Metastatic Melanoma patients.
    Detailed Description
    This is a Phase 1b open-label dose escalation trial of Ad/MG1-MAGEA3 and Pembrolizumab in patients with Metastatic Melanoma or Cutaneous Squamous Cell Skin Cancer that has failed prior standard of care treatments. This study will consist of two arms where the dose will be increased independently until the maximum tolerated dose (MTD) / maximum feasible dose (MFD) is reached. Arm 1 - Low-dose cyclophosphamide, followed by an Ad-MAGEA3 intramuscular (IM) prime, followed by intravenous (IV) administration of MG1-MAGEA3 and IV pembrolizumab. Arm 2 - Ad-MAGEA3 IM injection as a prime, followed by IV administration of MG1-MAGEA3, followed by intratumoral (IT) injection of MG1-MAGEA3 into tumors and IV pembrolizumab. In the Phase 1b Expansion for each arm, additional patients will be enrolled at the MTD/MDF as determined in Phase 1 in order to more thoroughly explore immune response, pharmacokinetics/dynamics, and safety for Malignant Melanoma patients who have failed standard therapies.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Metastatic Melanoma, Squamous Cell Skin Carcinoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm 1: Intravenous Dosing
    Arm Type
    Experimental
    Arm Description
    Low dose cyclophosphamide (300mg/ m2) at Day -3, then a fixed dose of Ad-MAGEA3 administered IM on study Day 1. Followed by one of 3 dose levels (escalation) of MG1-MAGEA3 administered as 2 intravenous (IV) doses at Day 15 and Day 18 and fixed dose pembrolizumab (200mg) beginning at either Week 6 or Day 1, depending on the cohort.
    Arm Title
    Arm 2: Intravenous followed by Intratumoral Dosing
    Arm Type
    Experimental
    Arm Description
    A fixed dose of Ad-MAGEA3 administered IM followed by Pembrolizumab on Day 1. MG1-MAGEA3 administered as an intravenous (IV) dose at Day 15, followed by intratumoral (IT) MG1-MAGEA3 on Day 22, Day 29, and Day 36. IT MG1-MAGEA3 booster injections may be continued every 3 weeks beginning at Day 43 (Week 6).
    Intervention Type
    Drug
    Intervention Name(s)
    Ad-MAGEA3
    Intervention Description
    Adenovirus vaccine expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen
    Intervention Type
    Drug
    Intervention Name(s)
    MG1-MAGEA3
    Intervention Description
    MG1 Maraba oncolytic virus expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen
    Intervention Type
    Drug
    Intervention Name(s)
    Pembrolizumab
    Other Intervention Name(s)
    Keytruda
    Intervention Description
    monoclonal antibody; checkpoint inhibitor of PD1
    Intervention Type
    Drug
    Intervention Name(s)
    Cyclophosphamide
    Intervention Description
    low-dose chemotherapy
    Primary Outcome Measure Information:
    Title
    Safety of Ad/MG1-MAGEA3 administration in Melanoma or Squamous Cell Skin Carcinoma
    Description
    Safety will be determined by assessing the severity and frequency of treatment emergent Adverse Events and clinical laboratory toxicity using NCI CTCAE v 5.0
    Time Frame
    6 months
    Title
    Determine the maximum tolerated dose (MTD)/ maximum feasible dose (MFD) of Ad/MG1-MAGEA3 in Melanoma or Squamous Cell Skin Carcinoma
    Description
    MTD/MFD of Ad/MG1-MAGEA3 administered by IV infusion alone and IV infusion followed by direct injection of tumor (IT injection) in Melanoma or Squamous Cell Skin Carcinoma
    Time Frame
    5 weeks
    Secondary Outcome Measure Information:
    Title
    Evaluate Overall Response
    Description
    Determine the overall response rate (Partial Response (PR) + Complete Response (CR))
    Time Frame
    2 years
    Title
    Evaluate Disease Control
    Description
    Determine Disease Control Rate (PR+CR+Stable Disease (SD))
    Time Frame
    2 years
    Title
    Evaluate PFS
    Description
    Progression free survival in months
    Time Frame
    2 years
    Title
    Evaluate Duration of Response, if any
    Description
    Duration of Response (CR, PR, SD) in months
    Time Frame
    2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Have histologically or cytologically confirmed diagnosis of locally advanced metastatic melanoma or cutaneous squamous cell carcinoma that has failed standard therapies For patients treated intratumorally, must have a lesion suitable for direct injection of MG1-MAGEA3 Have at least one tumor amenable to biopsy Have measurable disease via RECIST 1.1 criteria Adequate organ function and performance status Additional inclusion criteria present Exclusion Criteria: Prior treatment with any MAGE-A3 vaccine immunotherapy Prior systemic therapy for cancer within 4 weeks (8 weeks for lung radiation), and has recovered from chemo-related toxicities to Grade 1 or less Intolerant to prior PD1/PD-L1 therapy Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies or intra-tumoral injections. Known active CNS metastases and/or carcinomatous meningitis. Active autoimmune disease that has required systemic therapy in the past 2 years. Conditions likely to have resulted in splenic dysfunction. Known HIV/AIDS, active HBV or HCV infection. Additional Exclusion criteria exist
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Steve Bernstein, MD
    Organizational Affiliation
    Turnstone Biologics
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    MG1-MAGEA3 With Ad-MAGEA3 and Pembrolizumab in Patients With Previously Treated Metastatic Melanoma or Cutaneous Squamous Cell Carcinoma

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