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

NCT ID: NCT03773744

Last Updated: 2021-04-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-15
• Study Completion Date: 2021-12-31

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.

Conditions

Metastatic Melanoma; Squamous Cell Skin Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ad-MAGEA3

Intervention Type: DRUG

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

MG1-MAGEA3

Intervention Type: DRUG

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

Pembrolizumab

Intervention Type: DRUG

monoclonal antibody; checkpoint inhibitor of PD1

Cyclophosphamide

Intervention Type: DRUG

low-dose chemotherapy

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).

Group Type: EXPERIMENTAL

Ad-MAGEA3

Intervention Type: DRUG

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

MG1-MAGEA3

Intervention Type: DRUG

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

Pembrolizumab

Intervention Type: DRUG

monoclonal antibody; checkpoint inhibitor of PD1

Interventions

Ad-MAGEA3

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

Intervention Type: DRUG

MG1-MAGEA3

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

Intervention Type: DRUG

Pembrolizumab

monoclonal antibody; checkpoint inhibitor of PD1

Intervention Type: DRUG

Cyclophosphamide

low-dose chemotherapy

Intervention Type: DRUG

Other Intervention Names

Keytruda

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Turnstone Biologics, Corp.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steve Bernstein, MD

Role: STUDY_DIRECTOR

Turnstone Biologics

Other Identifiers

Ad/MG1-MAGEA3-003

Identifier Type: -

Identifier Source: org_study_id