Publication date: Jun 04, 2019
No safety concerns identified; no significant overlap of or unexpected toxicities 65% overall ORR with 9% CR (RECIST 1. 1) maintained Preliminary PFS of 12. 3 months Changes in T cell populations similar to single-agent PV-10 treatment KNOXVILLE, TN, June 03, 2019 (GLOBE NEWSWIRE) — ^A Provectus (OTCQB: PVCT) today announced that updated safety and response results as well as preliminary treatment durability and immune response results from the Company’s ongoing Phase 1b/2 study of PV-10 in combination with KEYTRUDA (pembrolizumab), an immune checkpoint inhibitor, were presented at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting, held in Chicago, IL from May 31-June 4, 2019.
Intralesional injection of oncolytic immunotherapy PV-10 can yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells. 1-5 PV-10 clinical development includes cutaneous melanoma and cancers of the liver, such as hepatocellular carcinoma, metastatic neuroendocrine tumors, and metastatic uveal melanoma, in both single-agent and combination therapy settings.
^A Treatment summary: Median of 4 cycles (mean 3. 7, range 1-5) and median of 5 injections of PV-10 (range 1-82); PV-10 was not administered after week 12.
^A Updated target lesion efficacy (best overall response): 77% complete response (CR), 80% ORR, and 87% clinical benefit; 75% CR in M1b patients and 100% CR in M1c patients.
^A Minimal intervention: 26% of patients achieved an overall objective response after 3 or less cycles of PV-10; 30% of target lesions achieved CR after 1 injection of PV-10 and 53% achieved CR after 3 injections or less.
^A Preliminary changes in peripheral blood mononuclear cells: Activated T cell populations increased during the PV-10 treatment interval; NK and NKT cell populations exhibited transient increases 1 week after PV-10 injections; cytotoxic, helper, and total T cell populations were stable.
Two patients in the Phase 1b studycE2€™s main cohort were refractory to checkpoint inhibition: 1 achieved a CR after previously being on OPDIVO^A(R) for 12 months and 1 withdrew after previously being on YERVOY^A(R) for 3 years due to the onset of myasthenia gravis.
Dominic Rodrigues, Vice Chair of the CompanycE2€™s Board of Directors, said, cE2€œThese trial results demonstrate the safety profile, treatment response, durability of response, and immune response of the PV-10-checkpoint inhibition combination after minimal PV-10 intervention. 7 Successful cancer combination therapy is achieved by pairing drugs that each show single-agent activity.
cE2€ Mr. Rodrigues added, cE2€œTogether with safety, response, biomarker, and quality of life data of single-agent PV-10 for the treatment of metastatic neuroendocrine tumors presented earlier today at ASCO, these advanced melanoma combination therapy data add to the abundance of drug activity information of PV-10 in both high and low mutation tumor types, and in both T cell and non-T cell inflamed tumor types.
cE2€ A copy of the ASCO poster presentation is currently available on ProvectuscE2€™ website at PV-10 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.
PV-10 is undergoing clinical study for adult solid tumor cancers like melanoma and cancers of the liver (including metastatic neuroendocrine tumors and metastatic uveal melanoma) and preclinical study for pediatric cancers like neuroblastoma5, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.
T cell mediated immunity after combination therapy with intralesional PV-10 and blockade of the PD-1/PD-L1 pathway in a murine melanoma model.
^A ^A ^A To date, clinical trial and expanded access patients have received the combination of PV-10 and checkpoint inhibition for advanced melanoma (+KEYTRUDA), mucosal melanoma of the vagina (+KEYTRUDA), Merkel cell carcinoma (+BAVENCIO^A(R)), breast cancer (+OPDIVO), Basal cell carcinoma (+ KEYTRUDA and ERIVEDGE^A(R)), and uveal melanoma metastatic to the liver (+OPDIVO and YERVOY).