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

NCT03773744 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: Ad/MG1-MAGEA3-003
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Metastatic Melanoma; Squamous Cell Skin Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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

  6 months

• 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

  5 weeks

Secondary Outcomes (4)

• Evaluate Overall Response

  2 years

• Evaluate Disease Control

  2 years

• Evaluate PFS

  2 years

• Evaluate Duration of Response, if any

  2 years

Study Arms (2)

Arm 1: Intravenous Dosing

EXPERIMENTAL

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; Drug: MG1-MAGEA3; Drug: Pembrolizumab; Drug: Cyclophosphamide

Arm 2: Intravenous followed by Intratumoral Dosing

EXPERIMENTAL

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; Drug: MG1-MAGEA3; Drug: Pembrolizumab

Interventions

Ad-MAGEA3 DRUG

Adenovirus vaccine expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen

Arm 1: Intravenous Dosing; Arm 2: Intravenous followed by Intratumoral Dosing

MG1-MAGEA3 DRUG

MG1 Maraba oncolytic virus expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen

Arm 1: Intravenous Dosing; Arm 2: Intravenous followed by Intratumoral Dosing

Pembrolizumab DRUG

monoclonal antibody; checkpoint inhibitor of PD1

Also known as: Keytruda

Arm 1: Intravenous Dosing; Arm 2: Intravenous followed by Intratumoral Dosing

Cyclophosphamide DRUG

low-dose chemotherapy

Arm 1: Intravenous Dosing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Turnstone Biologics, Corp.: lead

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Steve Bernstein, MD

  Turnstone Biologics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2018
• First Posted: December 12, 2018
• Study Start: February 15, 2020
• Primary Completion: October 30, 2020
• Study Completion: December 31, 2021
• Last Updated: April 6, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share