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PVSRIPO in Combination With Immune Checkpoint Blockade in Advanced PD-1 Refractory Melanoma (LUMINOS-102)

Description

This multi-center, open-label, randomized, Phase 2 will investigate the efficacy and safety of PVSRIPO alone (Arm 1) or in combination with an anti-PD-1 inhibitor (Arm 2). Following a six-participant safety run-in period, up to approximately 50 participants with cutaneous or mucosal melanoma who previously failed anti-PD-1 blockade will be randomized 1:1 to receive either PVSRIPO or PVSRIPO plus an anti-PD-1.

Status

Accepting new patients

Primary Study Objective(s)

The primary objective of this study is overall response rate. 

Core eligibility

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

Including patients who meet these criteria:

  • ≥ 18 years of age
  • Prior CDC-recommended vaccination series against PV, and has received a boost immunization with PV Inactivated (IPOL®; Sanofi-Pasteur SA) at least 1 week, but less than 6 weeks, prior to Day 1
    • Note: Patients who are unsure of their vaccination status must provide evidence of anti-PV immunity prior to enrollment, as applicable.
  • Biopsy proven (within 4 months of Day 1) unresectable cutaneous or mucosal melanoma
    • Note: Ocular melanoma is excluded.
  • Has ≥ 2 melanoma lesions that are accurately measurable by caliper or a radiological method according to RECIST 1.1 criteria
    • One lesion must be injectable- defined as a visible or palpable cutaneous, subcutaneous or nodal melanoma lesion ≥10 mm in longest diameter or multiple injectable melanoma lesions which in aggregate have a longest diameter of ≥10 mm and where the minimum lesion size is ≥5 mm
    • Note that visceral lesions (eg liver, lung, retroperitoneal, subpleural lesions) are not considered injectable for the purposes of this trial.
  • Had confirmed disease progression per iRECIST after receiving at least 6 weeks of treatment with an FDA-approved anti-PD-1/anti-PD-L1 therapy (as monotherapy or in combination), without experiencing a toxicity requiring permanent discontinuation of the anti-PD-1/anti-PD-L1. Patients treated with anti-PD-1 in the adjuvant setting and who have confirmed progression after at least 6 weeks of anti-PD-1 therapy are allowed.
    • NOTE: Patients with known BRAF mutation must have also failed or refused to receive BRAF-targeted therapy (alone or in combination with MEK inhibitor) to be eligible.
  • Eastern Cooperative Oncology Group (ECOG) status of 0-1
  • Serum lactate dehydrogenase (LDH) levels ≤ 3 x upper limit of normal (ULN)
  • Adequate bone marrow, liver and renal function as assessed by the following:
    • Hemoglobin ≥ 9.0 g/dl, patients may be transfused
    • Lymphocyte count ≥ 0.5 x 10^9/L (500 µL)
    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1500 µL)
    • Platelet count ≥ 100 x 10^9/L (100,000 µL) without transfusion
    • AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN), with the following exceptions: Patients with documented liver metastases: AST and ALT ≤ 5 x ULN; Patients with documented liver or bone metastases: ALP ≤ 5 x ULN
    • Serum bilirubin ≤ 1.5 x ULN with the following exception: Patients with known Gilbert disease: serum bilirubin level ≤ 3 x ULN
    • Estimated creatinine clearance ≥ 30 ml/min, per MDRD equation
    • Serum albumin ≥ 25 g/L (2.5 g/dL)
    • For patients not receiving therapeutic anticoagulation: INR, PT, PTT (or aPTT) ≤ 1.5 x ULN
  • Life expectancy of >12 weeks
  • Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for the study, and is willing/able to participate in the study

Declining patients who meet these criteria:

  • Symptomatic, untreated, or actively progressing CNS metastases. Participants with a history of treated CNS lesions are eligible, provided the following criteria are met:
    • No stereotactic radiotherapy within 7 days, or whole-brain radiotherapy within 14 days of Day 1
    • No ongoing requirement for corticosteroids to manage CNS disease. Anticonvulsant therapy at a stable dose is permitted.
    • Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan
  • History of leptomeningeal disease
  • Uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry
    • Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
    • Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment
  • Uncontrolled pleural effusion, pericardial effusion, or ascites
    • Patients with indwelling catheters (e.g., PleurX™) are allowed.
  • Uncontrolled or symptomatic hypercalcemia (>1.5 mmol/L ionized calcium or calcium >12 mg/dL or corrected serum calcium >ULN)
  • Active or history of autoimmune disease or immune deficiency within previous 2 years, with the following exceptions:
    • History of autoimmune-related hypothyroidism that is managed by thyroid replacement hormone
    • Type 1 diabetes mellitus that is well-controlled by an established insulin regimen
    • Eczema, psoriasis, or lichen simplex chronicus with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded), provided all of the following conditions are met:
      • Rash must cover <10% of body surface area
      • Disease is well-controlled at baseline and requires only low-potency topical corticosteroids
      • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within 12 months of Day 1
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
    • History of radiation pneumonitis in the radiation field (fibrosis) is allowed.
  • History of a positive HIV RNA test (HIV 1 or 2 RNA by PCR)
  • Known active hepatitis B virus (HBV) infection (chronic or acute)
    • NOTE: Participants with a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test are allowed.
  • Known active hepatitis C virus (HCV) infection
    • NOTE: History of positive HCV antibody test, but negative HCV RNA test is allowed.
  • Active tuberculosis
  • Significant cardiovascular disease, such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months of Day 1, unstable arrhythmia, or unstable angina
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 elimination half-lives- whichever is shorter, prior to treatment, or has not recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy are eligible.
    • Note: Anti-PD-1/PD-L1 within 4 weeks of Day 1 is allowed. If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
  • History of other malignancy within 2 years of Day 1, with the exception of those with a negligible risk of metastasis or death (e.g., resected cutaneous basal cell carcinoma, or other cancers with 5-year OS of >90%)
  • Severe infection within 4 weeks of Day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
    • Prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are allowed.
  • Prior allogeneic stem cell or solid organ transplantation
  • Treatment with a live, attenuated vaccine within 4 weeks of Day 1
  • Treatment with systemic immunosuppressive medication within 4 weeks of Day 1, with the following exceptions:
    • Participants who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible
    • Patients receiving mineralocorticoids (e.g., fludrocortisone), or systemic prednisone equivalent corticosteroid doses of <10mg per day are eligible for the study
    • Use of topical corticosteroids with occlusive dressings is prohibited
  • Known hypersensitivity to pembrolizumab, nivolumab or any of the respective excipients
  • A pregnant or nursing female, or women of child-bearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception starting from signed ICF through 150 days after last anti-PD-1 dose
  • History of human serum albumin allergy
  • History of neurological complications due to polio virus infection
  • History of agammaglobulinemia
  • History of worsening steroid myopathy (e.g., gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
  • Concurrent participation in a separate interventional clinical trial during this study
  • Any underlying medical condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromises the well-being) or that could prevent, limit, or confound protocol-specified assessments
     

Accepting new patients

 

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