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

Metastatic Melanoma Clinical Trial

— Pelican  

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Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03773744
• Other study ID #: Ad/MG1-MAGEA3-003
• Status: Withdrawn
• Phase: Phase 1
• Start date: February 15, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: April 2021
• Source: Turnstone Biologics, Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 31, 2021
• Est. primary completion date: October 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Melanoma
• Metastatic Melanoma
• Squamous Cell Skin Carcinoma

Intervention

Drug:
• Ad-MAGEA3
Adenovirus vaccine expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen
• MG1-MAGEA3
MG1 Maraba oncolytic virus expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen
• Pembrolizumab
monoclonal antibody; checkpoint inhibitor of PD1
• Cyclophosphamide
low-dose chemotherapy

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Turnstone Biologics, Corp.

Outcome

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