New chemoablative approach for hepatocellular carcinoma and metastatic liver disease

One patient with hepatocellular carcinoma (HCC) and one with colorectal cancer (CRC) metastatic to the liver demonstrated non-existent liver cancer after a single injection of PV-10, reports a study presented at the ESMO 17th World Congress on Gastrointestinal Cancer, 1-4 July, Barcelona, Spain.

Patients with HCC have a poor prognosis with median survivals of 10 to 11 months despite sorafenib use first line. Furthermore, liver metastases develop in nearly 20% of patients with stage II and 50% of patients with stage III colorectal cancer and represent the major cause death in this disease.

PV-10, a 10% solution of rose bengal originally used an agent to stain necrotic tissue in the cornea, has already demonstrated high rates of complete response and durable response in metastatic melanoma. In phase 2 data, presented in October 2014 at ESMO, 50% of a subgroup of 28 patients with stage III melanoma who had all their cutaneous lesions injected with PV-10 achieved a compete response and 71% achieved an overall response (complete and partial response). Investigators have also successfully ablated animal models of liver, renal, breast and pancreatic tumours with PV-10.

For the current study two cohorts of patients, one with non-resectable HCC (n=6 patients) and the second with other forms of cancer metastatic to the liver (n=7) underwent a single percutaneous injection of PV-10 guided by CT to one target lesion in the liver that was at least 1 cm in diameter (0.25 to 0.50 mL per cm³ lesion volume).

For the first analysis of five patients who underwent longer-term assessment, two patients showed no evidence of disease at more than 40 months follow-up according to RECIST and EASL criteria. The first patient was a 68 year old male with HCC (hepatitis B + cirrhosis) alive at 54 months follow-up with no evidence of disease, and the second a 61 year old male with metastatic CRC alive at 42 months follow-up with no evidence of disease. Furthermore, at up to 54 months follow-up 10 out of the initial 13 patients were alive, with one death due to cardiac comorbidity, one to serious adverse events and one to HCC progression.

Adverse events were generally limited to injection site reactions and photosensitivity and resolved without sequelae, with elevated liver enzymes observed during the first week after treatment.

“Having liver cancer patients alive at up to 54 months of follow-up with no evidence of disease is remarkable. This is even more extraordinary when you consider these patients received just one or two intralesional injections,” says Eric Wachter, the author of the abstract who co-developed PV-10. “The study suggests that PV-10 has moved beyond just melanoma and may be agnostic to tumour type.”

As with melanoma, PV-10 is believed to have a local chemoablative effect in HCC and metastatic liver disease where the agent enters lysosomes causing tumour necrosis that can stimulate immunological effects. Studies in melanoma patients injected with PV-10 have shown increased T cells in peripheral blood following injection including CD8+, CD4+, CD3+ and NKT.

Following these results Provectus Biopharmaceuticals, Inc. announced the signing of a Letter of Intent (LoI) with Boehringer Ingelheim China on July 2 to collaborate in bringing PV-10 to market in mainland China.

With an estimated 400,000 new cases of HCC in China each year and 372,000 deaths, there is an urgent need for new treatments. “The reason for the huge number of HCC cases in China is driven by population, hepatitis infection and aflatoxin, a fungal contaminant in maize that acts as a liver carcinogen,” says Peter Culpepper, CFO and COO of Provectus. Together Provectus and Boehringer Ingelheim China are planning phase 1b/2 studies of PV-10 in combination with standard of care (SOC) in liver cancer.

Reference

Poster Number: P-116. P Goldfarb, MD Russell Low, J Lyon, et al. Phase 1 Study of PV-10 for Chemoablation of Hepatocellular Cancer and Cancer Metastatic to the Liver.