Clinical Trials /

LUMINOS-102: PVSRIPO With or Without Immune Checkpoint Blockade in Patients With Advanced PD-1 Refractory Melanoma

NCT04577807

Description:

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.

Related Conditions:
  • Cutaneous Melanoma
  • Mucosal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PVSRIPO With or Without Immune Checkpoint Blockade in Patients With Advanced PD-1 Refractory Melanoma
  • Official Title: PVSRIPO in Combination With Immune Checkpoint Blockade in Advanced PD-1 Refractory Melanoma

Clinical Trial IDs

  • ORG STUDY ID: PVSRIPO ICI M201
  • NCT ID: NCT04577807

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
PVSRIPOArm 1: PVSRIPO Only
Anti-PD-1 Checkpoint InhibitorArm 2: PVSRIPO and anti-PD-1

Purpose

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.

Detailed 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). 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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1: PVSRIPO OnlyExperimentalPVSRIPO (up to 6x10^8 TCID50) administered via direct injection to amenable melanoma lesions given every 3-4 weeks
  • PVSRIPO
Arm 2: PVSRIPO and anti-PD-1ExperimentalPVSRIPO (up to 6x10^8 TCID50) administered via direct injection to amenable melanoma lesions and anti-PD-1 therapy given every 3-4 weeks as per the anti-PD-1 approved package insert
  • PVSRIPO
  • Anti-PD-1 Checkpoint Inhibitor

Eligibility Criteria

        Inclusion Criteria:

          1. ≥ 18 years of age

          2. 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

             a. Note: Patients who are unsure of their vaccination status must provide evidence of
             anti-PV immunity prior to enrollment, as applicable

          3. Biopsy proven (within 4 months of Day 1) unresectable cutaneous or mucosal melanoma

             a. Note: Ocular melanoma is excluded.

          4. Has disease that is accurately measurable by caliper or a radiological method
             according to RECIST 1.1 criteria

          5. At least 1 injectable 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

          6. Had confirmed disease progression after receiving at least 6 weeks of treatment with
             an FDA-approved anti-PD-1 therapy (as monotherapy or in combination), without
             experiencing a toxicity requiring permanent discontinuation of the anti-PD-1. 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.

             a. 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.

          7. Eastern Cooperative Oncology Group (ECOG) status of 0-1

          8. Serum lactate dehydrogenase (LDH) levels ≤ 3 x upper limit of normal (ULN)

          9. Adequate bone marrow, liver and renal function as assessed by the following:

               1. Hemoglobin ≥ 9.0 g/dl, patients may be transfused

               2. Lymphocyte count ≥ 0.5 x 10^9/L (500 µL)

               3. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1500 µL)

               4. Platelet count ≥ 100 x 10^9/L (100,000 µL) without transfusion

               5. 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

               6. Serum bilirubin ≤ 1.5 x ULN with the following exception: Patients with known
                  Gilbert disease: serum bilirubin level ≤ 3 x ULN

               7. Estimated creatinine clearance < 30 ml/min, per MDRD equation

               8. Serum albumin ≥ 25 g/L (2.5 g/dL)

               9. For patients not receiving therapeutic anticoagulation: INR, PT, PTT (or aPTT) ≤
                  1.5 x ULN

         10. Life expectancy of >12 weeks

         11. 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

        Exclusion Criteria:

          1. Symptomatic, untreated, or actively progressing CNS metastases. Participants with a
             history of treated CNS lesions are eligible, provided the following criteria are met:

               1. No stereotactic radiotherapy within 7 days, or whole-brain radiotherapy within 14
                  days of Day 1

               2. No ongoing requirement for corticosteroids to manage CNS disease. Anticonvulsant
                  therapy at a stable dose is permitted.

               3. 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

          2. History of leptomeningeal disease

          3. Uncontrolled tumor-related pain. Participants requiring pain medication must be on a
             stable regimen at study entry.

               1. 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

               2. 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

          4. Uncontrolled pleural effusion, pericardial effusion, or ascites a. Patients with
             indwelling catheters (e.g., PleurX™) are allowed.

          5. Uncontrolled or symptomatic hypercalcemia (>1.5 mmol/L ionized calcium or calcium >12
             mg/dL or corrected serum calcium >ULN)

          6. Active or history of autoimmune disease or immune deficiency within previous 2 years,
             with the following exceptions:

               1. History of autoimmune-related hypothyroidism that is managed by thyroid
                  replacement hormone

               2. Type 1 diabetes mellitus that is well-controlled by an established insulin
                  regimen

               3. 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:

             i. 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

          7. 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

             a. History of radiation pneumonitis in the radiation field (fibrosis) is allowed.

          8. History of a Positive HIV RNA test (HIV 1 or 2 RNA by PCR)

          9. Known active hepatitis B virus (HBV) infection (chronic or acute)

             a. NOTE: Participants with a negative HBsAg test and a positive total hepatitis B core
             antibody (HBcAb) test are allowed.

         10. Known active hepatitis C virus (HCV) infection

             a. NOTE: History of positive HCV antibody test, but negative HCV RNA test is allowed.

         11. Active tuberculosis

         12. 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

         13. Has received prior systemic anti-cancer therapy including investigational agents
             within 4 weeks (shorter interval for kinase inhibitors or other short half-life drugs
             may be allowed with Sponsor approval) prior to treatment, or has not recovered from
             all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2
             neuropathy may be eligible.

             a. Note: Anti-PD-1 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.

         14. 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%)

         15. Severe infection within 4 weeks of Day 1, including, but not limited to,
             hospitalization for complications of infection, bacteremia, or severe pneumonia

             a. 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:

               1. 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 with Sponsor approval

               2. Use of mineralocorticoids (e.g., fludrocortisone), or systemic prednisone
                  equivalent corticosteroid doses of <10mg per day are eligible for the study

               3. Use of topical corticosteroids with occlusive dressings is prohibited

         19. Known hypersensitivity to pembrolizumab, nivolumab or any of the respective excipients

         20. 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

         21. History of human serum albumin allergy

         22. History of neurological complications due to polio virus infection

         23. History of agammaglobulinemia

         24. History of worsening steroid myopathy (e.g., gradual progression of bilateral proximal
             muscle weakness, and atrophy of proximal muscle groups)

         25. Concurrent participation in a separate clinical trial during this study without
             Sponsor approval

         26. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:24 months
Safety Issue:
Description:Number of subjects achieving complete (CR) or partial response (PR), per RECIST 1.1 criteria, confirmed by repeat measurement, at least 4 weeks apart

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:24 months
Safety Issue:
Description:Overall survival (OS): time from randomization until death from any cause, through week 104
Measure:Duration of Response
Time Frame:24 months
Safety Issue:
Description:Duration of Response (DOR): time from objective response (per RECIST 1.1) until unequivocal disease progression or death, whichever occurs first
Measure:Disease Control Rate
Time Frame:24 months
Safety Issue:
Description:Disease control rate (DCR): the proportion of patients achieving CR, PR, or stable disease (SD) per RECIST1.1, as best response confirmed by repeat imaging at least 4 weeks apart.
Measure:Durable Response Rate
Time Frame:24 months
Safety Issue:
Description:Durable Response Rate (DRR): the proportion of participants with CR or PR (per RECIST 1.1) lasting at least 6 months

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Istari Oncology, Inc.

Last Updated

September 30, 2020