Reviewed and edited 26th September 2021
Updated September 21st 2021
Provectus Biopharmaceuticals Announces Presentation of Full Study Data from Metastatic Neuroendocrine Cancer Phase 1 Trial of PV-10® at European Society for Medical Oncology (ESMO) Congress 2021
KNOXVILLE, TN, Sept. 21, 2021 (GLOBE NEWSWIRE) — Provectus (OTCQB: PVCT) today announced that data from an ongoing clinical trial of investigational cancer immunotherapy PV-10 (rose bengal disodium) for the treatment of neuroendocrine tumors (NET) metastatic to the liver (mNET) refractory to somatostatin analogs (SSAs) and peptide receptor radionuclide therapy (PRRT) (NCT02693067) was presented at the European Society for Medical Oncology (ESMO) Congress, held online from September 16-21, 2021.
Highlights from the ESMO 2021mNET Presentation:
Baseline disease characteristics
N = 12 patients: 50% male; median age of 66 years (range 47-79)
Primary tumor sites: 7 small bowel (58%), 2 pancreas (17%), 1 caecal (8%), and 2 unknown (17%)
NET grades: 5 Grade 1 (42%) and 7 Grade 2 (58%)
Refractory to SSA and PRRT; all symptomatic progressive disease
Chromogranin A (CgA): median 1,585 μg/L (35-10,370)
Median number of injected lesions: 1 (1-4)
Median number of injection cycles: 1 (1-4); 8 patients (67%) received 1 PV-10 cycle; 4 patients received multiple cycles
Injection site pain in 9 of 12 patients (75%)
Grade 3 photosensitivity reaction in 1 patient; Grade 3 elevation of hepatic enzymes in 1 patient (resolved by Day 7); carcinoid flare in 2 patients
Injected-lesion efficacy (RECIST)
42% partial response (PR) and 42% objective response rate (ORR)
Patient-level efficacy (RECIST)
83%a disease control rate (DCR) (10 of 12 patients)
Median progression-free survival (PFS): 9.2 months (1.0-41.8)
Median overall survival (OS): 22.5 months (5.5-41.8); 6 patients (50%) undergoing response follow-up (data cut-off: April 30, 2021)
Upregulation of NK cells and activated CD4+ T cells observed in peripheral blood collected 7-28 days post-PV-10 injection
Biomarkers and quality of life (QOL)
CgA stable in 10 patients (83%)
Health-related QOL assessments stable or improved at one month in 8 of 11 patients (73%); maintained at 3 months in 6 of 10 patients (60%)
a Typographical error on the poster
A copy of the poster is available by clicking here.
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).
Results of Cohort 1 as follows:
Cohort 1 has fully enrolled, with 4 of 6 subjects male, median age 65yrs, range 47-72. Primary sites were: small bowel 3, pancreas 2, caecal 1; grade: Gd1 = 5, Gd2 = 1. All patients received prior Somatostatin Analogues (SSA) and PRRT. Median CgA was 645 (range 30-2819). To date 1 subject has received 4 PV-10 treatment cycles, 1 has received 2 cycles, and 4 have received a single cycle. Toxicity has been acceptable, including pain post procedure, carcinoid flare and nausea. LFT’s have remained stable. Overall QOL score was stable for 5 of 6 subjects. ORR in injected lesions is 50% (progression in 1 subject), with overall disease control of 84%. CgA response: 5 stable, 1 progression. One subject with “carcinoid pellagra” had rash resolution. Response follow-up is ongoing and additional efficacy and functional data will be presented. Hepatic IL PV-10 elicited no safety concerns with encouraging evidence of both local and systemic disease control. Enrolment to Cohort 2 is underway.
Phase 2 study combines PV-10 and Keytruda (Pembrolizumab) for treatment of metastatic Neuroendocrine Tumours
This trial is not yet on 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 in use and approved for multiple cancer types and on trial as a single agent for several trials involved 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.
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. Inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan.
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