Reviewed and edited 17th March 2022
Provectus Biopharmaceuticals Announces Presentation of Full Study Data from Metastatic Neuroendocrine Cancer Phase 1 Trial of PV-10® at ENETS Conference 2022
Provectus (OTCQB: PVCT) today announced that data from an ongoing clinical trial of investigational cancer immunotherapy PV-10 (rose bengal sodium) 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 annual conference of the European Neuroendocrine Tumor Society (ENETS), held from March 10-11, 2022 in a hybrid setting in Barcelona, Spain and online.
The oral presentation was made by the principal investigator of the clinical trial’s single center at The Queen Elizabeth Hospital (TQEH) in Adelaide, Australia: Tim Price, MBBS, DHlthSc (Medicine), FRACP, Head of Clinical Oncology Research and Chair of the combined Hematology and Medical Oncology Unit at TQEH, and Clinical Professor in the Faculty of Medicine at the University of Adelaide.
Highlights from the 2022 ENETS Presentation:
- Patient characteristics
- N = 12 patients: 50% male; median age of 66 years (range 47-79)
- Primary tumor sites: 7 small bowel (58%), 3 pancreas (25%), 1 caecal (8%), and 1 unknown (8%; likely pancreas)
- NET grades: 5 Grade 1 (42%) and 7 Grade 2 (58%)
- All patients were refractory to SSA (100%), and 11 received PRRT (92%) as part of their prior treatment
- All patients had symptomatic, progressive disease
- Baseline chromogranin A (CgA): median 1,585 µg/L (range 35-10,370)
- PV-10 treatment
- 4 patients (33%) received more than 1 dose (range 2-4)
- 8 patients (67%) received 1 dose
- All treatment-emergent adverse events (TEAEs) were Grade 1 or 2, primarily injection site pain (75%)
- Single subjects experienced Grade 3 TEAEs of photosensitivity reaction or transaminases increased
- Median progression-free survival (mPFS): 9.4 months (range 1.0-41.8)
- Median overall survival (mOS): 22.5 months (range 5.5-42.3); 4 patients alive
- Subgroup analysis of primary NET histology, pancreas vs intestine: mPFS 2.7 months vs 19.7 months; mOS 11.8 months vs 25.5 months
- Quality of life (QOL)
- Stable or improved health status and symptoms after 3 months in most patients
A recording of Dr. Price’s presentation and a copy of his slides are available – click here to watch on Provectus’ website.
Dominic Rodrigues, Vice Chair of the Company’s Board of Directors, said, “Study data continue to show encouraging local and systemic disease control, as well as symptom control, in a heavily pre-treated population and to support a role for monotherapy PV-10 as a treatment for neuroendocrine cancer patients who fail standard therapy.”
Mr. Rodrigues added, “PV-10-led combination therapies for neuroendocrine cancer patients may represent opportunities to improve quality of life and clinical outcomes. Front-line approaches may include combining liver-directed PV-10 therapy with systemically-delivered immune checkpoint inhibitors to enhance PV-10’s immune mechanisms, or using PV-10 to enhance the activity of cytotoxic treatments such as peptide receptor radionuclide therapy.”
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).
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.
General Clinical Trials Disclaimer
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. It’s very important to check the trial inclusion and exclusion criteria before making any contact. If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net
The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan.
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