THE PISCES STUDY: AMULTICENTER PHASE 2, OPEN-LABEL TRIAL OF INTRATUMORAL PIL-12 PLUS ELECTROPORATION IN COMBINATION WITH INTRAVENOUS PEMBROLIZUMAB IN PATIENTS WITH STAGE III/IVMELANOMA WHO ARE PROGRESSING ON EITHER PEMBROLIZUMAB OR NIVOLUMAB TREATMENT
Clinical Trial Information
Trial Contact: Frankos, Marie; Tan, Ciara Natasha
IRB No: 17.125.10
Protocol Abbrev: OMS-I103
Principal Investigator: Sajeve Samuel Thomas, MD
Phase: Drug: Phase II;Device: Non-significant Risk
Age Group: Adult
Secondary Protocol No: The Pisces Study
Treatment: pIL-12, Pembrolizumab, and Device: Immunopulse
Therapies Involved: Chemotherapy
ClinicalTrials.gov ID: NCT03132675
This will be a Phase 2 study of intratumoral pIL-12-EP plus IV pembrolizumab. Eligible patients will be those with pathological diagnosis of unresectable or metastatic melanoma who are progressing or have progressed on pembrolizumab or nivolumab..
• In order to be eligible for participation in this trial, the patient must meet all the following:
a.Pathologically documented unresectable melanoma, AJCC Stage III or IV. Patients must have histological or cytological confirmed diagnosis of unresectable melanoma with progressive locally advanced or metastatic disease.
b.Patients must be refractory to anti-PD-1 monoclonal antibodies (mAb) defined as pembrolizumab or nivolumab as either as monotherapy or in combination with other approved checkpoint inhibitors or targeted therapies according to their approved label, defined as (patients must meet all of the following criteria):
a.Received at least 4 doses of anti-PD1 mAb for pembrolizumab; minimum dose of 240 mg given every two weeks for nivolumab in monotherapy; minimum dose of 1 mg/kg given Q3W for nivolumab in combination with ipilimumab
b.Progressive disease after anti-PD1 mAb will be defined according to RECIST v1.1.
c.Documented disease progression within 24 weeks of the last dose of anti-PD1 mAb.
c.Resolution/improvement of anti-PD1 mAb-related AEs
a.No history of common toxicity criteria adverse events (CTCAE) Grade 4 irAEs from anti-PD1 mAb.
b.No history of CTCAE Grade 3 requiring steroid treatment (>10 mg/day prednisone or equivalent dose) for >12 weeks or CTCAE Grade 2 pneumonitis regardless of steroid treatment.
c.Minimum of 4 weeks (washout period) from the last dose of anti PD1 mAb.
d.Prior treatment with an approved BRAF inhibitor if BRAF V600 mutation-positive.
e.Age ≥ 18 years of age on day of signing informed consent.
f.Has a performance status of 0 or 1 on the ECOG Performance Scale.
g.Have measurable disease based on RECIST v1.1, with at least one anatomically distinct lesion. Lesion or lesions must meet all the following baseline criteria:
a.Accessible for electroporation,
b.Must be accurately measured in at least one dimension with a minimum size per RECIST v1.1.
h.Demonstrate adequate organ function as defined below. All screening laboratories should be performed within 10 days of treatment initiation.
System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥1.5 × 109/L Platelets ≥100 × 109/L Hemoglobin ≥9 g/dL or ≥5.6 mmol/L Renal Creatinine* OR ≤1.5 × the upper limit of normal (ULN) OR Measured or calculated creatinine clearance (CrCl) Glomerular filtration rate (GFR) can also be used instead of creatinine or CrCl ≥ 60 mL/min for patient with creatinine levels >1.5 × institutional ULN Hepatic Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels > 1.5× ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN OR ≤5 × ULN for patients with liver metastases Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT)
* Creatinine clearance should be calculated per institutional standard.
i.Women of childbearing potential must have negative serum or urine pregnancy test within 72 hours prior to receiving the first study drug administration.
j.For women of childbearing potential, must be willing to use an adequate method of contraception from 30 days prior to the first study drug administration and 120 days following last day study drug administration
k.Male patients of childbearing potential must be surgically sterile, or must agree to use adequate method of contraception during the study and at least 120 days following the last day of study drug administration.
l.Able and willing to provide written informed consent and to follow study instructions.