What is PV-10?

Described above as “Oncolytic Immunotherapy” but elsewhere as “Ablative Immunotherapy”, the latter indicates the method of administering the therapy i.e. tumour ablation. It’s more well known for trials in treating Melanoma where tumour ablation (albeit subcutaneous) is more common as a treatment.

Scientific Description: PV-10 causes acute oncolytic destruction of injected tumors, releasing damage associated molecular pattern molecules (DAMPs) and tumor antigens that initiate an immunologic cascade where local response by the innate immune system facilitates systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. T cell function can be further augmented by combining PV-10 with immune checkpoint inhibition. Sometimes it’s known as its short name “Rose Bengal“.

What is ‘Rose Bengal’?

It’s actually a 135 year old chemical stain, originally discovered in 1882, and for more than half a century used as a dye in cancer diagnosis.

Rose Bengal, in a 10% solution known as PV-10, has displayed greatest promise in the treatment of melanoma, where it was shown in an 80-patient Phase II trial to achieve a complete response rate in 50% of patients’ tumours and an overall response in 71%. A bystander effect was also seen in untreated lesions, suggesting a positive immune response, although it was more effective when all lesions were injected with PV-10.

Scientific Description: PV-10’s active pharmaceutical ingredient is rose bengal disodium (RB) (4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein disodium salt), a small molecule halogenated xanthene. PV-10 drug product is a bright rose red solution containing 10% w/v RB in 0.9% saline for injection, which is supplied in single-use glass vials containing 5 mL (to deliver) of solution and administered without dilution to solid tumors via intratumoral injection.

A Phase 1 Study of PV-10 Chemoablation of Neuroendocrine Tumours (NET) Metastatic to the Liver

This single-center Phase 1 study is being conducted at The Queen Elizabeth Hospital in Adelaide, Australia to evaluate the potential safety, tolerability, and preliminary efficacy of PV-10 in metastatic NET patients (NCT02693067). The primary endpoint for the trial is safety, and secondary endpoints include objective response rate (ORR) of injected target and measurable bystander lesions, target lesion somatostatin receptor expression, and biochemical response. Six patients in the first cohort each received one percutaneously-administered injection of PV-10 to one target lesion per treatment cycle. Patients in the second cohort can receive PV-10 injection of multiple lesions per cycle (2 of 6 patients in the second cohort have received at least one cycle of PV-10 thus far).

Further reading:

Phase 2 study combines PV-10 and Keytruda (Pembrolizumab) for treatment of metastatic Neuroendocrine Tumours

This trial is not yet on the Clinical Trials website but is a spin-off of the above trial and a very similar one for melanoma. It won the Australasian Gastro-Intestinal Trials Group’s New Concepts Award. Keytruda (Pembrolizumab) is a well-known immunotherapy treatment in use and approved for multiple cancer types and on trial as a single agent for several trials involving Neuroendocrine Neoplasms (mostly high grade).

PV-10-based Cancer Combination Therapy Clinical Trial Design Wins Australasian Gastro-Intestinal Trials Group’s New Concepts Award – Click here.