Clinical Trial 23341

• Overview

  Study Title:

  A Randomized, Controlled, Multicenter, Phase 3 Clinical Study Comparing Vusolimoqene Oderparepvec in Combination with Nivolumab Versus Treatment of Physician's Choice in Patients with Advanced Melanoma that Has Progressed on an Anti-PD-1 and an Anti-CTLA-4 Containing Treatment Regimen

  Summary:

  This is a randomized, controlled, multicenter, open-label Phase 3 clinical study comparing VO in combination with nivolumab versus Physician's Choice treatment for patients with unresectable Stage IIIb-IV cutaneous melanoma whose disease progressed on an anti PD-1 and an anti-CTLA-4 containing regimen (administered either as a combination regimen or in sequence) or who are not candidates for treatment with an anti-CTLA-4 therapy.

  Objective:

  Primary Objectives To compare survival of the study population treated with VO in combination with nivolumab versus physician s choice (PC) treatment Key Secondary To compare the time to progression or death of the study population following treatment with VO in combination with nivolumab versus treatment with PC To compare objective response rate (ORR) of the study population following treatment with VO in combination with nivolumab versus treatment with PC

• Treatments

  Therapies:

  Chemotherapy (NOS); Immunotherapy

  Medications:

  Albumin-Bound Paclitaxel (); BMS-936558 (Nivolumab); BMS-986016 (Relatlimab); DTIC (Dacarbazine); Dacarbazine (); Nivolumab (Opdivo); Pembrolizumab (Keytruda); Relatlimab (); Taxol (paclitaxel); Temodal (Temozolomide); Temozolomide (); Vusolimogene Oderparepvec (); paclitaxel ()

• Inclusion Criteria

  Inclusion Criteria:
  • Male or female who is 12 years of age or older and body weight >/=25 kg at the time of signed informed consent.
  • Patients with histologically or cytologically confirmed unresectable or metastatic Stage IIIb through IV/M1a through M1d cutaneous melanoma.
  • Confirmed disease progression (PD) on an approved anti-PD-1 and an anti-CTLA-4 treatment, administered either as a combination regimen (eg, nivolumab + ipilimumab) or in sequence. 1. Treatment with prior anti-PD-1 therapy must have continued for a minimum of 12 weeks 2. Patients who in the physician's judgement are not candidates for treatment with an anti-CTLA-4 antibody are eligible for the study if they have confirmed PD on any PD-1 antibody. 3. Disease progression must have been confirmed and documented using clinical or radiological assessment by 2 assessments at least 4 weeks apart. Radiological confirmation of PD can occur during the Screening period of this study.
  • Has documented BRAF V600 mutation status. Patients with BRAF mutation should have received prior BRAF-directed therapy (with or without a MEK inhibitor) prior to enrollment in the study, unless deemed not clinically indicated at Investigator's discretion due to concurrent medical condition or prior toxicity.
  • Has at least 1 measurable and injectable tumor of 1 cm or greater in longest diameter (or shortest diameter for lymph nodes).
  • Has adequate hematologic function.
  • Has adequate hepatic function.
  • Has adequate renal function.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1 for patients 18 years and older or a Lansky performance score (PSc) 80 or greater for patients 12 to 17 years of age.
  • Life expectancy of at least 3 months.
  • Female and male patients who meet the following criteria: Female patients are eligible if not pregnant or breastfeeding and if one of the following applies 1) is a woman of non-childbearing potential (WNCBP) OR 2) is a woman of childbearing potential (WOCBP) and must agree to use a highly effective contraception method during the treatment period and for at least a) 90 days after the last dose of RP1, or (b) 5 months after the last dose of nivolumab or Opdualag, or (c) 4 months after the last dose of pembrolizumab, or (d) 6 months after the last dose of dacarbazine, temozolomide, or paclitaxel, whichever is longer. b. Male patients are eligible to participate if they refrain from donating fresh unwashed semen plus either be abstinent from intercourse where pregnancy can occur (abstinent on a long term and persistent basis) and agree to remain abstinent OR must agree to use external condom and should also advise their partner to use a highly effective method of contraception, as a condom may break or leak for at least (a) 90 days after the last dose of RP1 or, (b) 3 months after the last dose of dacarbazine or temozolomide, or (c) 6 months after the last dose paclitaxel, whichever is longer. Nment.
  • Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin test within 72 hours before the first dose of study treatment.
  • Other criteria may apply.

• Exclusion Criteria

  Exclusion Criteria:
  • Primary mucosal or uveal melanoma.
  • More than 2 lines of systemic therapy for advanced melanoma.
  • Known acute or chronic hepatitis.
  • Known human immunodeficiency virus (HIV) infection.
  • Active significant herpetic infections or prior complications of Herpes Simplex Virus (HSV-1) infection.
  • Had systemic infection requiring IV antibiotics or other serious active infection requiring antimicrobial, antiviral, or antifungal treatment within 14 days prior to dosing.
  • With active significant herpetic infections or prior complications of HSV-1 infection.
  • Evidence of spinal cord compression or at high risk of spinal cord compression.
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis at time of screening.
  • Major surgery 2 weeks or less prior to starting study drug.
  • Prior malignancy active within the previous 3 years, except for locally curable cancers that have apparently been cured
  • History of significant cardiac disease including myocarditis or congestive heart failure or unstable angina, serious uncontrolled arrhythmia, cerebral vascular accident, myocardial infarction, or significant hypotension within 6 months of first dose of VO.
  • History of life-threatening toxicity related to prior immune.
  • Active, known, or suspected autoimmune disease requiring systemic treatment.
  • History of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
  • Prior oncolytic virus or other therapy given by intratumoral administration.
  • Requires intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
  • Has received a live vaccine within 28 days prior to the first dose of study treatment.
  • Systemic anticancer therapies within 5 half-lives or 4 weeks of the first dose, whichever is shorter.
  • Conditions requiring treatment with immunosuppressive doses (>10 mg per day of prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy within 14 days after enrollment.
  • History of allergy or sensitivity to study drug components (VO, nivolumab, pembrolizumab, relatlimab, dacarbazine, temozolomide or paclitaxel (albumin-bound paclitaxel dependent on cohort) or prior monoclonal antibody treatment.
  • Treatment with botanical preparations (e.g., herbal supplements or traditional Chines medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment.
  • Other criteria may apply.

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