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

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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.

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.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Squamous Cell Skin Carcinoma Drug: Ad-MAGEA3 Drug: MG1-MAGEA3 Drug: Pembrolizumab Drug: Cyclophosphamide Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : January 15, 2020
Estimated Primary Completion Date : October 30, 2020
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
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.
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

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).
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




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. Evaluate Overall Response [ Time Frame: 2 years ]
    Determine the overall response rate (Partial Response (PR) + Complete Response (CR))

  2. Evaluate Disease Control [ Time Frame: 2 years ]
    Determine Disease Control Rate (PR+CR+Stable Disease (SD))

  3. Evaluate PFS [ Time Frame: 2 years ]
    Progression free survival in months

  4. Evaluate Duration of Response, if any [ Time Frame: 2 years ]
    Duration of Response (CR, PR, SD) in months



Information from the National Library of Medicine

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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:

  • 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

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): NCT03773744


Contacts
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Contact: Tara Hollister 613-983-8272 tara.hollister@turnstonebio.com
Contact: Turnstone Patient Inquiry clinicalops@turnstonebio.com

Sponsors and Collaborators
Turnstone Biologics, Corp.
Investigators
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Study Director: Steve Bernstein, MD Turnstone Biologics
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Responsible Party: Turnstone Biologics, Corp.
ClinicalTrials.gov Identifier: NCT03773744    
Other Study ID Numbers: Ad/MG1-MAGEA3-003
First Posted: December 12, 2018    Key Record Dates
Last Update Posted: April 10, 2019
Last Verified: April 2019
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
Additional relevant MeSH terms:
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Carcinoma
Melanoma
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Squamous Cell
Cyclophosphamide
Pembrolizumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological