Phase 1 clinical trial of single agent PV-10 for the treatment of symptomatic neuroendocrine tumors (NET) metastatic to the liver

An interesting trial from Provectus Biopharmaceuticals Inc.  Phase 1 results were presented at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting, held in Chicago, IL from May 31-June 4, 2019

In an ogoing Phase 1 clinical trial of single agent PV-10 for the treatment of symptomatic neuroendocrine tumors (NET) metastatic to the liver. 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. PV-10 clinical development includes cutaneous melanoma, hepatocellular carcinoma, and metastatic liver cancers such as uveal melanoma in single-agent and combination therapy settings.

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.

What is the trial doing and where is the trial located?

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

Further reading:

The NET Clinical Trial document: click here

The ASCO poster for the NET trial: click here

ASCO trial update: click here

Thanks for listening

 

New Radiotracer Can Identify Nearly 30 Types of Cancer – SNMMI – 68Ga-FAPI PET/CT

see citation below

New radiotracer can identify nearly 30 types of cancer (including NETs). Future potential for therapeutic application. This is a different type of radiotracer being currently being used in the approved market for NETs.  It’s availability and timeline is not yet known.

Date: June 7, 2019

Source: Society of Nuclear Medicine and Molecular Imaging

Summary: A novel class of radiopharmaceuticals has proven effective in non-invasively identifying nearly 30 types of malignant tumors. Using 68Ga-FAPI PET/CT, researchers were able to image the tumors with very high uptake and image contrast, paving the way for new applications in tumor characterization, staging and therapy.

Red more here. https://www.snmmi.org/NewsPublications/NewsDetail.aspx?ItemNumber=31744

Watch this space for more data on availability timeline and what type of NETs were used in the trial will follow.

To learn more about the currently approved Ga68 PET scans, check out these articles

Gallium 68 PET Scans – Into the Unknown

Neuroendocrine Cancer: Ga68 PET Scan – a game changer? 

If you can see it, you can normally detect it

Theranostics for Neuroendocrine Cancer – a find and destroy mission

Citation for graphic:

FIGURE: 68Ga-FAPI PET/CT in patients reflecting 15 different tumor entities. Maximum-intensity projections of 68Ga-FAPI PET/CT in patients reflecting 15 different histologically proven tumor entities (sorted by uptake in descending order). Ca = cancer; CCC = cholangiocellular carcinoma; CUP = carcinoma of unknown primary; MTC = medullary thyroid cancer; NET = neuroendocrine tumor.

The authors of “68Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer” include Clemens Kratochwil, Thomas Lindner, Labidi Abderrahim, Walter Mier, Hendrik Rathke, Manuel Röhrich and Frederik L. Giesel, Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany; Paul Flechsig, Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany, and Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany; Annette Altmann, Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany, and Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany; Sebastian Adeberg, Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany, and Heidelberg Institute for Radiation Oncology, Heidelberg, Germany; Hauke Winter, Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany, and Department of Surgery, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany; Peter K. Plinkert, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Heidelberg, Germany; Frederik Marme, Department of Obstetrics and Gynecology, University Hospital Heidelberg, Heidelberg, Germany, and Department of Obstetrics and Gynecology, University Hospital Mannheim, Mannheim, Germany; Matthias Lang, Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany; Hans Ulrich Kauczor, Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany, and Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany; Dirk Jäger, Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany, and Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center, Heidelberg, Germany; Jürgen Debus, Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany, Heidelberg Institute for Radiation Oncology, Heidelberg, Germany, and Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center, Heidelberg, Germany; and Uwe Haberkorn, Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany, Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany, and Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany.

About the Society of Nuclear Medicine and Molecular Imaging

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and medical organization dedicated to advancing nuclear medicine and molecular imaging, vital elements of precision medicine that allow diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes.

SNMMI’s more than 17,000 members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings, and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit www.snmmi.org.

Thanks for reading

Ronny

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LUTATHERA (PRRT) – NETTER 2 Clinical Trial for Grade 2/Grade 3 Neuroendocrine Neoplasms

netter 2

Brief Summary:

The NETTER-1 trials led to the approval of Lu177 (or Lutathera), more commonly known in the community as Peptide Receptor Radio Therapy (PRRT).  This led to an explosion of availability across the world but many gaps in service remain.

Many PRRT spin off trials are in the pipeline looking at different types of PRRT, mainly using slightly different radionuclides and techniques.  However, NETTER-2 builds on the success of the approved version formally known as Lutathera.

The aim of NETTER-2 is to determine if Lutathera in combination with long-acting octreotide prolongs PFS in GEP-NET patients with high proliferation rate tumors (G2 and G3), when given as a first line treatment compared to treatment with high dose (60 mg) long-acting octreotide. Somatostatin analog (SSA) naive patients are eligible, as well as patients previously treated with SSAs in the absence of progression.

This is a phase 3 trial that will be hoping for 222 participants at multiple locations.

This article will be fleshed out in due course. No locations listed yet.  Not recruiting yet.  Criteria listed – important section if this trial interests you. Clinical Trials document here.

In the meantime, read more about Lutathera (PRRT) by clicking here.

This looks like a very exciting development.

Thanks for reading

Ronny

I’m also active on Facebook. Like my page for even more news. I’m also building up this site here: Ronny Allan

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

Ronny Allan is an award winning patient leader and advocate for Neuroendocrine Cancer.


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