Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma.

Abstract

BACKGROUND:

While programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) antagonists have improved the prognosis for many patients with melanoma, around 60% fail therapy. PVSRIPO is a non-neurovirulent rhinovirus:poliovirus chimera that facilitates an antitumor immune response following cell entry via the poliovirus receptor CD155, which is expressed on tumor and antigen-presenting cells. Preclinical studies show that oncolytic virus plus anti-PD-1 therapy leads to a greater antitumor response than either agent alone, warranting clinical investigation.

METHODS:

An open-label phase I trial of intratumoral PVSRIPO in patients with unresectable melanoma (American Joint Committee on Cancer V.7 stage IIIB, IIIC, or IV) was performed. Eligible patients had disease progression on anti-PD-1 and V-raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen activated protein kinase kinase (MEK) inhibitors (if BRAF mutant). The primary objective was to characterize the safety and tolerability of PVSRIPO. Twelve patients in four cohorts received a total of 1, 2 or 3 injections of PVSRIPO monotherapy, with 21 days between injections.

RESULTS:

PVSRIPO injections were well tolerated with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs) reported. All adverse events (AEs) were grade (G) 1 or G2 (G1 pruritus most common at 58%); all but two PVSRIPO-treatment related AEs were localized to the injected or adjacent lesions (n=1 G1 hot flash, n=1 G1 fatigue). Four out of 12 patients (33%) achieved an objective response per immune-related response criteria (two observations, 4 weeks apart), including 4/6 (67%) who received three injections. In the four patients with in-transit disease, a pathological complete response (pCR) was observed in two (50%) patients. Following study completion, 11/12 patients (92%) reinitiated immune checkpoint inhibitor-based therapy, and 6/12 patients (50%) remained without progression at a median follow-up time of 18 months.

CONCLUSION:

Intratumoral PVSRIPO was well tolerated. Despite the limited number of PVSRIPO treatments relative to the overall lesion burden (67% patients>5 lesions), intratumoral PVSRIPO showed promising antitumor activity, with pCR in injected as well as non-injected lesions in select patients.

TRIAL REGISTRATION NUMBER:

NCT03712358.

• Authors: Georgia M Beasley, Smita K Nair, Norma E Farrow, Karenia Landa, Maria Angelica Selim, Carol Ann Wiggs, Sin-Ho Jung, Darell D Bigner, Andrea True Kelly, Matthias Gromeier, April Ks Salama
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 9 Issue 4 (04 2021) ISSN: 2051-1426 [Electronic] England
• PMID: 33875611 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Topics

• Adult
• Aged
• Aged, 80 and over
• Female
• Humans
• Male
• Melanoma (immunology, therapy)
• Middle Aged
• North Carolina
• Oncolytic Virotherapy (adverse effects)
• Oncolytic Viruses (immunology, pathogenicity)
• Poliovirus (immunology, pathogenicity)
• Rhinovirus (immunology, pathogenicity)
• Skin Neoplasms (immunology, therapy, virology)
• Time Factors
• Treatment Outcome