Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Orange, California and other locations
Dates
study started
estimated completion

Description

Summary

A Phase 2 study to investigate the efficacy and safety of PVSRIPO alone or in combination with a programmed death receptor-1 (anti-PD-1) inhibitor.

Official Title

PVSRIPO in Combination With Immune Checkpoint Blockade in Advanced PD-1 Refractory Melanoma

Details

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 6 participant safety run-in period, up to approximately 50 participants with cutaneous or mucosal melanoma who previously failed anti-PD-1/L1-based therapy will be randomized 1:1 to receive either PVSRIPO or PVSRIPO plus an anti-PD-1.

Keywords

Melanoma PVSRIPO Anti-PD-1 Checkpoint Inhibitor

Eligibility

You can join if…

Open to people ages 18 years and up

  1. ≥ 18 years of age
  2. Prior CDC-recommended vaccination series against PV, and has received a boost immunization with trivalent IPOL® (Sanofi-Pasteur SA) at least 1 week, but less than 6 weeks, prior to Day 1
  3. NOTE: Patients who are unsure of their vaccination status must provide evidence of anti-PV immunity prior to enrollment, as applicable
  4. Has biopsy proven unresectable cutaneous, acral or mucosal melanoma and is willing to undergo tumor biopsy prior to the first dose of study drugs and at prespecified intervals during the study (see Table 1).
  5. Submission of an archival biopsy sample is allowed in lieu of the baseline tumor biopsy, provided the tissue is ≤4 months old and the participant received no intervening systemic/intratumoral anti-cancer therapy since the biopsy was acquired.
  6. Must have at least 1 lesion that is amenable to biopsy. The lesion must be safely accessible as determined by the investigator and should not be located at sites that require significant risk procedures to biopsy. Examples of sites considered to be of significant risk include but are not limited to the following: the brain, lung, mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach, or bowel wall.
  7. Has ≥ 2 melanoma lesions that are accurately measurable by caliper or a radiological method according to RECIST 1.1 criteria
  8. 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
  9. Note that visceral lesions (eg, liver, lung, retroperitoneal, subpleural lesions) are not considered injectable for the purposes of this trial.
  10. Has confirmed disease progression per iRECIST after receiving at least 6 weeks of treatment with an FDA-approved anti-PD-1/L1 therapy (as monotherapy or in combination) without experiencing a toxicity requiring permanent discontinuation of the anti-PD-1/L1. Patients treated with anti-PD-1/L1 in the adjuvant setting and who have confirmed progression after at least 6 weeks of anti-PD-1/L1 therapy are allowed.
  11. 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.
  12. Eastern Cooperative Oncology Group (ECOG) status of 0-1
  13. Serum lactate dehydrogenase (LDH) levels ≤ 3 x upper limit of normal (ULN)
  14. Adequate bone marrow, liver and renal function as assessed by the following:
  15. Hemoglobin ≥ 9.0 g/dl, patients may be transfused
  16. Lymphocyte count ≥ 0.5 x 109/L (500 µL)

  17. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500 µL)

  18. Platelet count ≥ 100 x 109/L (100,000 µL) without transfusion

  19. 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

  1. Serum bilirubin ≤ 1.5 x ULN with the following exception: Patients with known

Gilbert disease: serum bilirubin level ≤ 3 x ULN

  1. Measured or calculated (per institutional standards) creatinine clearance ≥ 30 ml/min (GRF can also be used in place of creatinine clearance)
  2. For patients not receiving therapeutic anticoagulation: INR, PT, PTT (or aPTT) ≤ 1.5 x ULN
  3. Life expectancy of >12 weeks
  4. . 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

You CAN'T join if...

  1. Has biopsy-proven ocular melanoma
  2. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. Participants with a history of treated CNS lesions are eligible, provided the following criteria are met:
  3. No stereotactic radiotherapy within 7 days, or whole-brain radiotherapy within 14 days of Day 1
  4. No ongoing requirement for corticosteroids to manage CNS disease. Anticonvulsant therapy at a stable dose is permitted.
  5. 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
  6. History of leptomeningeal disease
  7. Uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry.
  8. 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
  9. 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
  10. Uncontrolled pleural effusion, pericardial effusion, or ascites a. Patients with indwelling catheters (e.g., PleurX™) are allowed.
  11. Active or history of autoimmune disease or immune deficiency within previous 2 years, with the following exceptions:
  12. History of autoimmune-related hypothyroidism that is managed by thyroid replacement hormone
  13. Type 1 diabetes mellitus that is well-controlled by an established insulin regimen
  14. 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:
  15. Rash must cover <10% of body surface area

ii. Disease is well-controlled at baseline and requires only low-potency topical corticosteroids

iii. 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

  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
  2. History of radiation pneumonitis in the radiation field (fibrosis) is allowed.
  3. History of a positive HIV RNA test (HIV 1 or 2 RNA by PCR)
  4. Known active hepatitis B virus (HBV) infection (chronic or acute)
  5. NOTE: Participants with a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test are allowed.
  6. . Known active hepatitis C virus (HCV) infection
  7. NOTE: History of a positive HCV antibody test, but negative HCV RNA test is allowed.
  8. . Active tuberculosis
  9. . 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
  10. . 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
  11. Note: Anti-PD-1/L1 within 4 weeks prior to Day 1 is allowed
  12. If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
  13. . 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%)
  14. . Severe infection within 4 weeks of Day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  15. Prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are allowed.
  16. . Prior allogeneic stem cell or solid organ transplantation
  17. . Treatment with a live, attenuated vaccine within 4 weeks of Day 1
  18. . Treatment with systemic immunosuppressive medication within 4 weeks of Day 1, with the following exceptions:
  19. 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
  20. Patients receiving mineralocorticoids (e.g., fludrocortisone), or systemic prednisone equivalent corticosteroid doses of <10mg per day are eligible for the study
  21. . Known hypersensitivity to pembrolizumab, nivolumab, or any of the respective excipients
  22. . Requires therapeutic anticoagulation and cannot discontinue anticoagulation safely during the day prior, day of, and day after each PVSRIPO injection
  23. NOTE: Participants receiving anticoagulation with warfarin at the time of study entry are allowed if they can be transitioned to an alternative anticoagulant (eg, low molecular weight heparin or direct oral anticoagulants) prior to the first dose of PVSRIPO. Anyone transitioned from warfarin to an oral anticoagulant prior to the first dose of PVSRIPO should have an INR <1.5x upper limit of normal in order to participate. Antiplatelet agents (eg, aspirin, clopidogrel, etc.) are not considered anticoagulants for the purposes of this study (ie, are allowed)
  24. . 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
  25. . History of human serum albumin allergy
  26. . History of neurological complications due to polio virus infection
  27. . History of agammaglobulinemia
  28. . Concurrent participation in a separate interventional clinical trial during this study.
  29. . 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 participant's well-being) or that could prevent, limit, or confound protocol-specified assessments

Locations

  • UC Irvine Medical Center, Chao Family Comprehensive Cancer Center accepting new patients
    Orange California 92868 United States
  • HonorHealth Research Institute accepting new patients
    Scottsdale Arizona 85258 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Istari Oncology, Inc.
ID
NCT04577807
Phase
Phase 2
Study Type
Interventional
Last Updated