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.
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
Drug | Synonyms | Arms |
---|
Ad-MAGEA3 | | Arm 1: Intravenous Dosing |
MG1-MAGEA3 | | Arm 1: Intravenous Dosing |
Pembrolizumab | Keytruda | Arm 1: Intravenous Dosing |
Cyclophosphamide | | Arm 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
Name | Type | Description | Interventions |
---|
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. | - Ad-MAGEA3
- MG1-MAGEA3
- Pembrolizumab
- 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). | - 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: | Withdrawn |
Lead Sponsor: | Turnstone Biologics, Corp. |
Last Updated
April 6, 2021