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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Melanoma; Squamous Cell Skin Carcinoma
• Intervention / Treatment: Drug: Ad-MAGEA3; Drug: MG1-MAGEA3; Drug: Pembrolizumab; Drug: Cyclophosphamide

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: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Turnstone Biologics, Corp.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2020
• Primary Completion (Anticipated): October 30, 2020
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: December 10, 2018
• First Submitted That Met QC Criteria: December 11, 2018
• First Posted (Actual): December 12, 2018

Study Record Updates

• Last Update Posted (Actual): April 6, 2021
• Last Update Submitted That Met QC Criteria: April 1, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Neoplasms, Squamous Cell; Carcinoma; Melanoma; Carcinoma, Squamous Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Pembrolizumab
• Other Study ID Numbers: Ad/MG1-MAGEA3-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No