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

NCT04577807 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: LUMINOS-102
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (6)

• Overall Response

  The number of patients achieving confirmed complete (CR) or partial response (PR), per RECIST 1.1 criteria

  24 months

• Number of Participants Experiencing a Treatment-emergent Adverse Event

  The number of participants experiencing a treatment-emergent adverse event

  24 months

• Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs)

  The number of participants experiencing an AESI or irAE

  24 months

• Number of Participants Discontinuing Study Treatment Due to Adverse Event(s)

  Number of participants discontinuing study treatment due to adverse event(s)

  24 months

• Changes From Baseline in the Number of CD8+ Tumor Infiltrating Lymphocytes (TILs)

  Changes from baseline in the number of CD8+ tumor infiltrating lymphocytes (TILs)

  24 months

• Changes From Baseline in PD-L1 Expression

  Changes from baseline in PD-L1 expression

  24 months

Secondary Outcomes (6)

• Overall Survival

  24 months

• Duration of Response

  24 months

• Disease Control Rate

  24 months

• DCR-6 Months

  24 months

• Durable Response Rate

  24 months

Other Outcomes (13)

• Lerapolturev Mechanism of Action and Predictors of Response to Lerapolturev With or Without Anti-PD-1 in Patients Who Have Failed Anti-PD1/L1 -Based Therapy

  24 months

• ORR Based on iRECIST

  24 months

• DOR Based on iRECIST

  24 months

Study Arms (2)

Arm 1: Lerapolturev

EXPERIMENTAL

Lerapolturev (up to 1.6x10\^9 TCID50) administered via direct injection of up to 6 lesions

Biological: Lerapolturev

Arm 2: Lerapolturev and anti-PD-1

EXPERIMENTAL

Lerapolturev (up to 1.6x10\^9 TCID50) administered via direct injection of up to 6 lesions. Anti-PD-1 therapy given as per the anti-PD-1 approved package insert.

Biological: Lerapolturev; Biological: Anti-PD-1 Checkpoint Inhibitor

Interventions

Lerapolturev BIOLOGICAL

Lerapolturev administered via direct lesion injection

Arm 1: Lerapolturev; Arm 2: Lerapolturev and anti-PD-1

Anti-PD-1 Checkpoint Inhibitor BIOLOGICAL

Anti-PD-1 Checkpoint Inhibitor administered per package insert instructions

Arm 2: Lerapolturev and anti-PD-1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• Istari Oncology, Inc.: lead

Study Sites (12)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

Orlando Health U7 Health Cancer Center

Orlando, Florida, 32806, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Cancer Treatment Centers of America

Zion, Illinois, 60099, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Henry Ford Health System

Detroit, Michigan, 48208, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University of Pittsburgh Hillman Cancer Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Oncology -Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

West Virginia University Medical Center

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Head of Operations
• Organization: Istari Oncology

info@istarioncology.com

919-245-7662

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2020
• First Posted: October 8, 2020
• Study Start: November 17, 2020
• Primary Completion: November 15, 2024
• Study Completion: November 15, 2024
• Last Updated: September 19, 2025
• Results First Posted: September 19, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)