Clinical trial NCT03773744: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Metastatic Melanoma
Squamous Cell Skin Carcinoma
Lead sponsor: Turnstone Biologics, Corp.
Sponsor class: INDUSTRY
First posted: 2018-12-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety of Ad/MG1-MAGEA3 administration in Melanoma or Squamous Cell Skin Carcinoma
timeFrame: 6 months
measure: Determine the maximum tolerated dose (MTD)/ maximum feasible dose (MFD) of Ad/MG1-MAGEA3 in Melanoma or Squamous Cell Skin Carcinoma
timeFrame: 5 weeks
Secondary outcomes:
measure: Evaluate Overall Response
timeFrame: 2 years
measure: Evaluate Disease Control
timeFrame: 2 years
measure: Evaluate PFS
timeFrame: 2 years
measure: Evaluate Duration of Response, if any
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Turnstone Biologics
name: Steve Bernstein, MD
role: STUDY_DIRECTOR
References: