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OncoSec OMS-I103 (PISCES): A multicenter, phase 2, open-label study of intratumoral tavokinogene telseplasmid (tavo, pIL-12) plus electroporation in combination with intravenous pembrolizumab in patients with stage III/IV melanoma, who are progressing on either pembrolizumab or nivolumab treatment

Description

This will be a phase 2 study of intratumoral tavokinogene telseplasmid (tavo; pIL-12) electroporation (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.

Status

Accepting new patients

Primary Study Objective(s)

The primary objectives of this trial are to assess:

  • Overall response rate (ORR) by blinded independent central review
  • Safety and tolerability of the combined treatment in subjects with unresectable or metastatic melanoma who previously have progressed on prior approved anti-PD-1 antibodies either as monotherapy or in combination with another approved checkpoint inhibitor
  • Duration of response, ORR, immune OR, Progression Free Survival (PFS), immune PFS, and overall survival of combination therapy
  • Long-term safety and tolerability of the combination therapy

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who:

  • Have pathologically documented unresectable melanoma, American Joint Committee on Cancer (AJCC) version 8, Stage III or IV (Subjects must have histological or cytological confirmed diagnosis of unresectable melanoma with progressive locally advanced or metastatic disease.)
  • Are refractory to anti-PD-1 monoclonal antibodies (mAb) pembrolizumab or nivolumab either as monotherapy or in combination with other approved checkpoint inhibitors or targeted therapies according to their approved label and must meet all of the following criteria:
    • Received treatment of FDA-approved anti-PD-1 mAb (dosed per label of the country providing the clinical site) for at least 12 weeks
    • Has progressive disease after anti-PD-1 mAb defined according to RECIST v1.1. (The initial evidence of PD is to be confirmed by a second assessment, no less than 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression. This determination is made by the investigator; the sponsor will collect imaging scans for retrospective analysis. Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression.)
    • Has documented disease progression within 12 weeks of the last dose of anti-PD-1 mAb (Subjects who were re treated with anti-PD-1 mAb and subjects who were on maintenance with anti-PD-1 mAb will be allowed to enter the study as long as there is documented PD within 12 weeks of the last treatment date (with anti-PD-1 mAb)
  • Have resolution/improvement of anti-PD-1 mAb related AEs (including immune related AEs; irAEs) back to Grade 0 1 and ≤10 mg/day prednisone (or equivalent dose) for irAEs for at least 2 weeks prior to the first dose of study drug, with:
    • No history of common toxicity criteria adverse events (CTCAE) Grade 4 irAEs from anti-PD-1 mAb
    • 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
    • Minimum of 4 weeks (washout period) from the last dose of anti-PD-1 mAb
  • Had prior treatment with an approved BRAF inhibitor if BRAF V600 mutation positive
  • Are at least 18 years old on the day of signing informed consent
  • Have a performance status of 0 or 1 on the ECOG Performance Scale, collected within seven days of initial treatment
  • Have measurable disease based on RECIST v1.1, with at least one anatomically distinct lesion that meet all the following baseline criteria:
    • Are accessible for electroporation
    • Be accurately measured in at least one dimension
  • Demonstrate adequate organ function (All screening laboratories should be performed within 10 days of treatment initiation.)
  • If have childbearing potential, must have negative serum or urine pregnancy test within 72 hours prior to receiving the first study drug administration (If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.)
  • If have 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
  • If male, 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
  • Are able and willing to provide written informed consent and to follow study instructions

Excluding patients who:

  • Have disease that is suitable for local therapy administered with curative intent
  • Have a diagnosis of uveal or mucosal melanoma
  • Have a known additional malignancy that is progressing or requires active treatment within the past 3 years(Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.)
  • Have clinically active CNS metastases (Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least four weeks by repeat imaging.)
  • Have more than three visceral sites of metastases (not including nodal metastases associated with visceral organs)
  • Have stage IVc melanoma with liver or bowel metastases
  • Have had an allogenic tissue/solid organ transplant
  • Have an electronic pacemaker or defibrillator
  • Have a history of human immunodeficiency virus (HIV)
  • Have a history of Hepatitis B or C infections or known to be positive for Hepatitis B antigen (HBsAg) or Hepatitis B virus (HBV) DNA or Hepatitis C antibody or RNA. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay
  • Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy in dosing exceeding 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy within seven days prior to the first dose of study drug (The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor.)
  • Have received a live virus vaccination within 30 days of the first dose of treatment.
  • Have severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
  • Have received a transfusion of blood products (including platelets or red blood cells) or colony stimulating factors (including G CSF, GM CSF or recombinant erythropoietin) within four weeks prior to study Cycle 1, Day 1 (baseline)
  • Have a history of (non infectious) pneumonitis that required steroids or current pneumonitis
  • Have a history of interstitial lung disease
  • Have an active infection requiring systemic therapy
  • Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent
  • Participated in another clinical study of an investigational anti-cancer agent or has used an investigational device within 30 days of screening
  • Have had intervening therapy following confirmed progression on anti PD-1 therapy or anti-PD-1 combination therapy with the exception of approved BRAF/MEK inhibitor combinations (PD-1 combination therapy is acceptable as the last prior treatment and may include anti-PD-1, anti-CTLA4 antibody combination therapy and anti-PD-1 combinations with investigational or injectable therapy.)
  • Have known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study
  • Are pregnant or breast-feeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment