Clinical Trials /

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

NCT03773744

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. 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.

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

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: Ad/MG1-MAGEA3-003
  • NCT ID: NCT03773744

Conditions

  • Metastatic Melanoma
  • Squamous Cell Skin Carcinoma

Interventions

DrugSynonymsArms
Ad-MAGEA3Arm 1: Intravenous Dosing
MG1-MAGEA3Arm 1: Intravenous Dosing
PembrolizumabKeytrudaArm 1: Intravenous Dosing
CyclophosphamideArm 1: Intravenous Dosing

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1: Intravenous DosingExperimentalLow 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.
  • Ad-MAGEA3
  • MG1-MAGEA3
  • Pembrolizumab
  • Cyclophosphamide
Arm 2: Intravenous followed by Intratumoral DosingExperimentalA 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).
  • Ad-MAGEA3
  • MG1-MAGEA3
  • Pembrolizumab

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

Primary Outcome Measures

Measure:Safety of Ad/MG1-MAGEA3 administration in Melanoma or Squamous Cell Skin Carcinoma
Time Frame:6 months
Safety Issue:
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

Secondary Outcome Measures

Measure:Evaluate Overall Response
Time Frame:2 years
Safety Issue:
Description:Determine the overall response rate (Partial Response (PR) + Complete Response (CR))
Measure:Evaluate Disease Control
Time Frame:2 years
Safety Issue:
Description:Determine Disease Control Rate (PR+CR+Stable Disease (SD))
Measure:Evaluate PFS
Time Frame:2 years
Safety Issue:
Description:Progression free survival in months
Measure:Evaluate Duration of Response, if any
Time Frame:2 years
Safety Issue:
Description:Duration of Response (CR, PR, SD) in months

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Turnstone Biologics, Inc.

Last Updated

April 8, 2019