Metastatic Melanoma, Squamous Cell Skin Carcinoma
Conditions
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.
Interventions
DRUGAd-MAGEA3
Adenovirus vaccine expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen
DRUGMG1-MAGEA3
MG1 Maraba oncolytic virus expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen
DRUGPembrolizumab
monoclonal antibody; checkpoint inhibitor of PD1
DRUGCyclophosphamide
low-dose chemotherapy
Sponsors
Turnstone Biologics, Corp.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Ad/MG1-MAGEA3 administration in Melanoma or Squamous Cell Skin Carcinoma | 6 months | 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 |
| Determine the maximum tolerated dose (MTD)/ maximum feasible dose (MFD) of Ad/MG1-MAGEA3 in Melanoma or Squamous Cell Skin Carcinoma | 5 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Overall Response | 2 years | Determine the overall response rate (Partial Response (PR) + Complete Response (CR)) |
| Evaluate Disease Control | 2 years | Determine Disease Control Rate (PR+CR+Stable Disease (SD)) |
| Evaluate PFS | 2 years | Progression free survival in months |
| Evaluate Duration of Response, if any | 2 years | Duration of Response (CR, PR, SD) in months |
Outcome results
None listed