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

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: NCT03773744
Recruitment Status : Not yet recruiting
First Posted : December 12, 2018
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Turnstone Biologics, Corp.

Tracking Information
First Submitted Date  ICMJE December 10, 2018
First Posted Date  ICMJE December 12, 2018
Last Update Posted Date April 10, 2019
Estimated Study Start Date  ICMJE January 15, 2020
Estimated Primary Completion Date October 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2018)
  • Safety of Ad/MG1-MAGEA3 administration in Melanoma or Squamous Cell Skin Carcinoma [ Time Frame: 6 months ]
    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 [ Time Frame: 5 weeks ]
    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
Original Primary Outcome Measures  ICMJE
 (submitted: December 11, 2018)
  • Safety of Ad/MG1-MAGEA3 administration in Melanoma or Squamous Cell Skin Carcinoma [ Time Frame: 6 months ]
    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-E6E7 in Melanoma or Squamous Cell Skin Carcinoma [ Time Frame: 5 weeks ]
    MTD/MFD of Ad/MG1-E6E7 administered by IV infusion alone and IV infusion followed by direct injection of tumor (IT injection) in Melanoma or Squamous Cell Skin Carcinoma
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2018)
  • Evaluate Overall Response [ Time Frame: 2 years ]
    Determine the overall response rate (Partial Response (PR) + Complete Response (CR))
  • Evaluate Disease Control [ Time Frame: 2 years ]
    Determine Disease Control Rate (PR+CR+Stable Disease (SD))
  • Evaluate PFS [ Time Frame: 2 years ]
    Progression free survival in months
  • Evaluate Duration of Response, if any [ Time Frame: 2 years ]
    Duration of Response (CR, PR, SD) in months
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MG1-MAGEA3 With Ad-MAGEA3 and Pembrolizumab in Patients With Previously Treated Metastatic Melanoma or Cutaneous Squamous Cell Carcinoma
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Melanoma
  • Squamous Cell Skin Carcinoma
Intervention  ICMJE
  • Drug: Ad-MAGEA3
    Adenovirus vaccine expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen
  • Drug: MG1-MAGEA3
    MG1 Maraba oncolytic virus expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen
  • Drug: Pembrolizumab
    monoclonal antibody; checkpoint inhibitor of PD1
    Other Name: Keytruda
  • Drug: Cyclophosphamide
    low-dose chemotherapy
Study Arms  ICMJE
  • Experimental: Arm 1: Intravenous Dosing
    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.
    Interventions:
    • Drug: Ad-MAGEA3
    • Drug: MG1-MAGEA3
    • Drug: Pembrolizumab
    • Drug: Cyclophosphamide
  • Experimental: Arm 2: Intravenous followed by Intratumoral Dosing
    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).
    Interventions:
    • Drug: Ad-MAGEA3
    • Drug: MG1-MAGEA3
    • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: December 11, 2018)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date October 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tara Hollister 613-983-8272 tara.hollister@turnstonebio.com
Contact: Turnstone Patient Inquiry clinicalops@turnstonebio.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03773744
Other Study ID Numbers  ICMJE Ad/MG1-MAGEA3-003
Has Data Monitoring Committee Yes
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  ICMJE
Plan to Share IPD: No
Responsible Party Turnstone Biologics, Corp.
Study Sponsor  ICMJE Turnstone Biologics, Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Steve Bernstein, MD Turnstone Biologics
PRS Account Turnstone Biologics, Corp.
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP