FDA Grants Orphan Drug Designation to Novel Immunotherapy in Advanced Melanoma

The FDA granted an Orphan Drug designation to the novel immunotherapy PVSRIPO for the treatment of patients with advanced melanoma of stage IIB-IV.

The FDA has granted an Orphan Drug designation to the novel immunotherapy PVSRIPO for the treatment of patients with advanced melanoma of stage IIB-IV, Istari Oncology, Inc., announced in a press release.1

The agent is under evaluation currently in a phase 2 study known as LUMINOS-102 (NCT04577807), which follows a successful phase 1 study of PVSRIPO as monotherapy in patients with anti-PD-1 refractory advanced melanoma.

“We are encouraged by the data from our phase 1 trial presented at last year’s Society for Immunotherapy of Cancer (SITC) 2020 annual meeting,” said Garrett Nichols, MD, MS, chief medical officer, Istari Oncology, in a statement. “We plan to build upon that success with LUMINOS-102. As those data and the data from our other solid tumor trials emerge, we will continue to work closely with the FDA toward the goal of bringing PVSRIPO to market.”

Among 6 of 12 patients who had received 3 injections of PVSRIPO, the objective response rate was 67% with responses observed in 4 patients. The data suggest this agent, alone or combined with anti-PD-1, holds promise for these patients and that this therapy may help rekindle anti-tumor activity among patients failing treatment with immune checkpoint inhibitors. The findings also showed that intratumoral PVSRIPO was well tolerated, and no serious adverse events (AEs) or dose-limiting toxicities were observed.2

LUMINOS-102, an open-label trial, aims to determine the safety, tolerability, and initial efficacy of PVSRIPO intratumoral injection alone and in combination with a PD-1 inhibitor as treatment of patients with advanced, unresectable melanoma who previously failed anti-PD-1 therapy. The first patient is expected to be dosed during the first quarter of 2021.1

Approximately 50 patients are expected to enroll in the study who have cutaneous or mucosal melanoma who have previously failed anti-PD-1 blockade. The patients will be randomized 1:1 to receive either PVSRIPO alone or in combination with an anti-PD-1 inhibitor.

The primary end points of the study include objective response rate, the incidence of study treatment discontinuation due to AEs, and frequency and severity of treatment-emergent AEs and of special interest AEs. Secondary end points also include overall survival, duration of response, disease control rates, durable response rate, and progression-free survival.

To be included in the study, patients must have had a prior Centers for Disease Control-recommended vaccination series against PV, have ≥ 2 melanoma lesions, confirmed disease progression per iRECIST after at least 6 weeks of an FDA-approved anti-PD-1/PD-L1 therapy, and an ECOG performance status of 0 or 1. Patients also must have a serum lactate dehydrogenase level ≤ 3 x upper limit of normal; adequate bone marrow, liver, and renal function; and a life expectancy of > 12 weeks.

Patients will be ineligible to enroll in the study if they have symptomatic, untreated, or actively progression central nervous system metastases; a history of leptomeningeal disease; uncontrolled tumor-related pain; uncontrolled pleural effusion, pericardial effusion, or ascites; or uncontrolled or symptomatic hypercalcemia.

“We are happy to kick off the new year with the announcement that our request for an Orphan Drug designation has been granted to PVSRIPO for the treatment of advanced melanoma. This is just 1 of the many milestones to come in 2021 as we continue to drive the clinical development of PVSRIPO across multiple indications,” stated Matt Stober, president and chief executive officer, Istari Oncology.

PVSRIPO is known to activate a patient’s innate and adaptive immune system so that it can facilitate an anti-tumor response, establishing long-term immunologic memory to prevent the return of cancer. This therapy aims to address the significant unmet need in advanced melanoma as most of these patients received treatment with immune checkpoint inhibitors and many either do not respond or later become resistant and require other options, which remain limited.


1. Istari Oncology announces FDA grants Orphan Drug designation for PVSRIPO for the treatment of advanced melanoma. News Release. Istari Oncology, Inc. January 11, 2021. Accessed January 11, 2021. https://bwnews.pr/3i0oZ3Y

2. Istari Oncology presents positive data from phase 1 study of PVSRIPO in patients with unresectable treatment refractory melanoma at The Society for Immunotherapy of Cancer (SITC) 35th anniversary annual meeting. News Release. Istari Oncology, Inc. November 9, 2020. Accessed January 11, 2021. https://bit.ly/3oAad6s