Provectus Announces Updated Results from Phase 1B Trial of PV-10 in Combination with KEYTRUDA® for Treatment of Advanced Melanoma at ASCO 2019

Provectus Announces Updated Results from Phase 1B Trial of PV-10 in Combination with KEYTRUDA® for Treatment of Advanced Melanoma at ASCO 2019

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).

Concepts Keywords
Active Pharmaceutical Ingredient Immunotherapy
Adaptive Immune System Checkpoint nave Disease
Australia KEYTRUDA mucosal melanoma
Biomarker Neuroblastoma
Biotechnology Bengal melanoma
Blockade Ocular melanoma
Blood Tumors
Breast Systemic anti tumor
Brisbane KEYTRUDA Merkel carcinoma
Bristol Myers Squibb Hepatocellular carcinoma
California Biotechnology
Carcinoma Nivolumab
CD4 Melanoma
CD8 Ipilimumab
Chicago Medicine
Clinical Trial Clinical medicine
Clinical Trials Cancer
Cohort Antineoplastic drugs
Combination Therapy Breakthrough therapy
Congress Immune system
CR 80 Cancer treatments
Cytotoxic Bristol-Myers Squibb
Darmstadt Pembrolizumab
England Pharmaceutical use patent
Genentech Uveal melanoma
Germany Cancers
Glass Melanoma April NCT02557321
Halogenated Tumor
Hepatocellular Carcinoma Treatments metastatic melanoma
ICH Drug product
Immune Checkpoint Inhibitor Active pharmaceutical ingredient
Immunity Chemical small molecules
Immunogenic Process pharmaceutical grade
Immunotherapy Stage biotechnology
Innate Immune System
Intellectual Property
Italy
Kenilworth
Lesion
Liver
Lymphocytes
M1b
Manchester
Median
Melanoma
Merck
Merck KGaA
Metastatic
Murine
Mutation
Myasthenia Gravis
Naples
Nave
Neuroblastoma
Neuroendocrine Tumors
NIH
NKT
Ocular Melanoma
Oncolytic
Orphan Drug
Osteosarcoma
OTCQB
Patent
Pediatric
Pharmaceutical
Primary Endpoint
Qin
Refractory
Registered Trademark
Rhabdomyosarcoma
Rodrigues
Rose Red
Saline Injection
Salt
San Francisco
Sarcoma
Securities
Securities Exchange Commission
Small Molecule
Solid Tumor
SPIE
Subcutaneous
Tolerability
Trademark
Tumor
Tumor Antigens
Uveal Melanoma
Vagina
Xenograft
YERVOY

Semantics

Type Source Name
gene UNIPROT NAA50
gene UNIPROT SPEN
gene UNIPROT LYPD4
drug DRUGBANK Vismodegib
pathway BSID Basal cell carcinoma
disease DOID Basal cell carcinoma
disease MESH Basal cell carcinoma
disease DOID Merkel cell carcinoma
disease MESH breast cancer
disease DOID breast cancer
pathway BSID Breast cancer
disease MESH Merkel cell carcinoma
disease DOID mucosal melanoma
gene UNIPROT TNC
gene UNIPROT TNNC1
gene UNIPROT FOXG1
gene UNIPROT CD274
gene UNIPROT RPL17
gene UNIPROT PDCD1
disease DOID Colon cancer
disease MESH Colon cancer
gene UNIPROT COL4A2
disease MESH ICH
gene UNIPROT DYRK3
gene UNIPROT IK
gene UNIPROT ARID1B
gene UNIPROT ARID3A
disease DOID ocular melanoma
drug DRUGBANK Rose bengal free acid
disease DOID neuroblastoma
disease MESH neuroblastoma
disease DOID osteosarcoma
disease MESH osteosarcoma
disease DOID rhabdomyosarcoma
disease MESH rhabdomyosarcoma
disease DOID Ewing sarcoma
disease MESH Ewing sarcoma
disease MESH multiple
pathway BSID Adaptive Immune System
pathway BSID Release
pathway BSID Innate Immune System
gene UNIPROT MAGEE1
gene UNIPROT ARID1A
disease MESH tumor
disease MESH development
disease DOID cutaneous melanoma
disease MESH hepatocellular carcinoma
disease DOID hepatocellular carcinoma
disease MESH neuroendocrine tumors
disease MESH uveal melanoma
disease DOID uveal melanoma
gene UNIPROT ANP32B
gene UNIPROT TNFSF13
disease MESH men
gene UNIPROT ELL
gene UNIPROT BEST1
disease MESH myasthenia gravis
disease DOID myasthenia gravis
disease DOID cancer
drug DRUGBANK Pembrolizumab
drug DRUGBANK Nonoxynol-9
disease MESH Melanoma
pathway BSID Melanoma
disease DOID Melanoma

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