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

Completed · Phase 2

Conditions studied: Melanoma

In brief

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

Key facts

Study ID

NCT04577807

Run by

Istari Oncology, Inc.

People needed

27

Starts

2020-11-17

Expected to finish

2024-11-15

Last updated by the study team

2025-09-19

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• ≥ 18 years of age
• 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
• Has biopsy proven unresectable cutaneous melanoma and is willing to undergo tumor biopsy prior to the first dose of study drugs and at prespecified intervals during the study
• Patients with ocular, acral or mucosal melanoma are not eligible
• Patients with M1c or M1d disease are NOT eligble.
• 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.
• 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.
• 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.
• Has had confirmed progression of disease (PD) while receiving at least 6 weeks (> 1 dose) of an FDA-approved anti-PD-1/L1 therapy (as monotherapy or in combination) for the treatment of melanoma. Note the following details:
• Initial PD as defined by RECIST v1.1
• Confirmation of PD per iRECIST must occur by repeat assessment ≥ 4 weeks from initial evidence of PD, in the absence of rapid clinical progression.
• Those who discontinue anti-PD-1/L1 therapy after at least 6 weeks (> 1 dose) and have confirmed PD per iRECIST within 12 weeks of their last anti-PD-1/L1 dose are also eligible, provided the anti-PD-1/L1 was not stopped due to toxicity requiring permanent discontinuation
• Those treated with anti-PD-1/L1 in the adjuvant setting and who have biopsy-confirmed progression either while receiving anti-PD-1/L1-based therapy or ≤ 12 weeks after their last dose of anti-PD-1/L1 therapy are allowed NOTE: Adjuvant is defined as therapy received after surgical resection of disease such that the patient has no evidence of disease when the anti-PD-1/L1 therapy is initiated. 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

You may not qualify if…

• Has biopsy-proven ocular, acral or mucosal melanoma
• Has M1c or M1d disease
• No more than one prior systemic anti-cancer regimen (monotherapy or combination) for management of melanoma. Additional details noted below:
• Adjuvant anti-cancer therapy administered ≥ 6 months prior to the first injection of lerapolturev does NOT count as a line of treatment.
• Patients with BRAF mutant melanoma may enroll if they have received ≤ 2 prior lines of systemic anti-cancer therapy only if one of those lines of therapy was a BRAF-targeted regimen (alone or in combination with MEK inhibitor).
• A line of therapy is defined as a regimen in which at least 2 doses of systemic anti-cancer therapy (monotherapy or combination) was administered, and the regimen was discontinued because of progressive 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
• Grade ≥2 pleural effusion, pericardial effusion, or ascites
• Active or history of autoimmune disease or immune deficiency within previous 2 years, with the following exceptions:
• History of autoimmune-related endocrinopathy (e.g. adrenal insufficiency, hypothyroidism, Type 1 diabetes mellitus, etc.) that is managed by hormone replacement therapy (e.g. hydrocortisone, thyroid hormone, insulin, etc.)
• Eczema, psoriasis, or lichen simplex chronicus with dermatologic manifestations only (eg, 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
• 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.
• History of a positive HIV RNA test (HIV 1 or 2 RNA by PCR)
• 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.
• Known active hepatitis C virus (HCV) infection
• a. NOTE: History of a 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

Where it is running

• HonorHealth Research Institute — Scottsdale, Arizona, United States
• Orlando Health U7 Health Cancer Center — Orlando, Florida, United States
• Rush University Medical Center — Chicago, Illinois, United States
• Cancer Treatment Centers of America — Zion, Illinois, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Henry Ford Health System — Detroit, Michigan, United States
• Hackensack University Medical Center — Hackensack, New Jersey, United States
• University of Pittsburgh Hillman Cancer Center — Pittsburgh, Pennsylvania, United States
• Vanderbilt University Medical Center — Nashville, Tennessee, United States
• Texas Oncology -Baylor Charles A. Sammons Cancer Center — Dallas, Texas, United States
• Virginia Commonwealth University — Richmond, Virginia, United States
• West Virginia University Medical Center — Morgantown, West Virginia, United States

Full record on ClinicalTrials.gov

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