Clinical Trials /

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



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:
  • Melanoma
Recruiting Status:



Phase 2

Trial Eligibility



  • Brief Title: LUMINOS-102: 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

  • NCT ID: NCT04577807


  • Melanoma


Anti-PD-1 Checkpoint InhibitorArm 2: PVSRIPO and anti-PD-1


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). 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.

Trial Arms

Arm 1: PVSRIPO OnlyExperimentalPVSRIPO (up to 6x10^8 TCID50) administered via direct injection to amenable melanoma lesions given every 3 or 4 weeks
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 or 4 weeks as per the anti-PD-1 approved package insert
  • 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 trivalent 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. 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).

               1. 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

               2. 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.

          4. Has ≥ 2 melanoma lesions that are accurately measurable by caliper or a radiological
             method according to RECIST 1.1 criteria

               1. 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

               2. Note that visceral lesions (eg, liver, lung, retroperitoneal, subpleural lesions)
                  are not considered injectable for the purposes of this trial.

          5. 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.

             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.

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

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

          8. 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. Measured or calculated (per institutional standards) creatinine clearance ≥ 30
                  ml/min (GRF can also be used in place of creatinine clearance)

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

          9. Life expectancy of >12 weeks

         10. 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

        Exclusion Criteria:

          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:

               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

          3. History of leptomeningeal disease

          4. 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

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

          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

               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

             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 a positive HCV antibody test, but negative HCV RNA test is

         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 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

               1. Note: Anti-PD-1/L1 within 4 weeks prior to Day 1 is allowed

               2. If participant received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting study

         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

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

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

         20. Requires therapeutic anticoagulation and cannot discontinue anticoagulation safely
             during the day prior, day of, and day after each PVSRIPO injection

             a. 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)

         21. 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

         22. History of human serum albumin allergy

         23. History of neurological complications due to polio virus infection

         24. History of agammaglobulinemia

         25. Concurrent participation in a separate interventional clinical trial during this

         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 participant's 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:Overall Response Rate (ORR)
Time Frame:24 months
Safety Issue:
Description:The proportion of patients achieving confirmed complete (CR) or partial response (PR), per RECIST 1.1 criteria

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:24 months
Safety Issue:
Description:Overall survival (OS): time from treatment group assignment until death from any cause.
Measure:Duration of Response
Time Frame:24 months
Safety Issue:
Description:Duration of Response (DOR): time from confirmed objective response (CR or PR 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 confirmed CR, confirmed PR, or stable disease (SD) per RECIST1.1, as best response.
Measure:DCR-6 months
Time Frame:24 months
Safety Issue:
Description:Disease control rate-6months (DCR-6mo): the proportion of patients achieving confirmed CR (any duration), confirmed PR (any duration) or SD (≥ 6 months) per RECIST 1.1 as best response.
Measure:Durable Response Rate
Time Frame:24 months
Safety Issue:
Description:Durable Response Rate (DRR): the proportion of participants with confirmed CR or PR (per RECIST 1.1) lasting at least 6 months
Measure:Progression-free survival (PFS)
Time Frame:24 months
Safety Issue:
Description:Progression-free survival (PFS): time (number of months) from treatment group assignment until date of documented radiologic disease progression per RECIST 1.1 or death due to any cause, whichever comes first


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Istari Oncology, Inc.

Last Updated

August 13, 2021