On November 6, 2022 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported highly positive top-line results from the pivotal Phase III ZIRCON study (Zirconium in Renal Cancer Oncology, NCT03849118) of its investigational renal (kidney) cancer positron emission tomography (PET) imaging agent, TLX250-CDx (89Zr-DFO-girentuximab) (Press release, Telix Pharmaceuticals, NOV 6, 2022, View Source [SID1234623168]). The study has met its co-primary and secondary endpoints.

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The study results delivered 86% sensitivity and 87% specificity, exceeding the pre-determined threshold required to demonstrate the ability of TLX250-CDx to reliably detect the clear cell phenotype and provide a non-invasive method of diagnosing the presence and spread of ccRCC. The study has also met the key secondary endpoint, achieving 85% sensitivity and 89% specificity in detecting ccRCC in tumours <4cm ("T1a" classification), currently a significant clinical challenge in the diagnosis of ccRCC.

A total of 300 patients were dosed with TLX250-CDx resulting in 284 evaluable patients. Each patient received a single dose of TLX250-CDx and a histological tumour sample from surgical resection was used as the truth comparator.

The results mean that, for the first time, urologists and urologic oncologists may have a non-invasive way to determine if small renal masses are the clear cell phenotype, the most aggressive and common form of renal malignancy. TLX250-CDx has received "Breakthrough Designation" from the FDA.1
Investigators in the ZIRCON study commented:2

A/Prof Brian Shuch, MD, Director, Kidney Cancer Program, UCLA Institute of Urologic Oncology (Los Angeles, California) said, "The positive result from the study is a critical step in better diagnosing clear cell renal cancer. Having an imaging product like TLX250-CDx will be so important in managing the continued increase in incidence of small renal masses and reducing the need for unnecessary invasive surgery for lesions that in the prior era were often found to be benign at the time of surgery."

Mr Gregory Jack, F.R.A.C.S., General Urological Surgeon Austin Health and Olivia Newton John Cancer Centre (Melbourne, Australia) added, "Kidney cancer is a diagnostic dilemma for the majority of our patients. Without biopsy or surgery, we can’t currently give them the information they need. Based on this result from the ZIRCON Phase III study, TLX250-CDx may help us to be more accurate in who we treat, whilst also providing reassurance for those patients who don’t need treatment."

Professor Françoise Kraeber-Bodéré, MD, PhD, Nuclear Medicine Department – CHU Nantes (Nantes, France), said, "Results from the Phase III ZIRCON study of TLX250-CDx should represent a major milestone in the management of small renal lesions and the diagnosis of clear cell renal cell carcinoma. There is so much potential in optimal targeting of CAIX, paving the way for better staging of this neoplasia and a theranostic approach."

Based on these outstanding results Telix intends to file a BLA for regulatory approval with the FDA and global regulatory agencies as a positron emission tomography/computed tomography (PET/CT) imaging agent for use in the characterisation of indeterminate renal masses previously identified on CT or MRI as ccRCC or non-ccRCC. Potential future utility may include active surveillance, surgical staging and treatment response assessment and the Company is actively engaged in clinical research at leading cancer centres to demonstrate the potential of these indications.

Dr Colin Hayward, Chief Medical Officer at Telix said: "The excellent sensitivity and specificity demonstrated in the ZIRCON study, validates that the CAIX target could be just as ground-breaking in ccRCC as PSMA3 and its application in PSMA-PET imaging has been for prostate cancer. It could optimise surgical intervention – particularly in the incidence of very small renal masses. These results provide confidence that TLX250-CDx is an important tool not only for initial diagnosis but potentially also for active surveillance and disease staging."

On November 6, 2022 Asieris Pharmaceuticals, a global biopharmaceutical company specializing in the discovery and development of innovative drugs for the treatment of genitourinary tumors and other major diseases, reported that Hexvix, a drug used for the diagnosis for bladder cancer, completed the first patient dose in Phase III bridging trial (Press release, Asieris Pharmaceuticals, NOV 6, 2022, View Source [SID1234623167]).

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The study is a prospective, self-controlled, multicenter Phase Ⅲ trial aimed at investigating the additional detection rate and safety of Hexvix and blue light cystoscopy (BLC) versus white light cystoscopy in patients with non-muscle invasive bladder cancer (NMIBC) (CIS, Ta, T1).

This study will be led by Peking Union Medical College Hospital and the Chinese Academy of Medical Sciences. Professor Li Hanzhong, head of the Department of Surgery at Peking Union Medical College Hospital, will serve as the Principal Investigator to lead a team of top experts in the field of bladder cancer in China to carry out this study. The company plans to file a new drug application with the NMPA in the future pending clinical trial progress and meaningful data.

In January 2021, Asieris entered into a license agreement with Photocure ASA (Photocure, OSE:PHO), a bladder cancer specialty company based in Oslo, Norway, to obtain the exclusive registration and commercialization rights of Hexvix in mainland China and Taiwan.

In December 2021, Hexvix was put into pilot use in the Boao Lecheng International Medical Tourism Pilot Zone in Hainan Province and the first prescription in China was issued at Hainan General Hospital, with the first patient operated successfully. It received approval from the National Medical Products Administration (NMPA) for phase III clinical trials in the first quarter of 2022 and was included in the real-world clinical data pilot program.

On November 4, 2022 ENB Therapeutics, Inc., a biotechnology company pioneering a new and differentiated class of therapeutics targeting the endothelin B receptor (ETBR) inhibitor, reported that it will present a scientific poster on ENB-003 at the 2022 Summit for Cancer Immunotherapy in Montreal, Quebec November 19-21, 2022 (Press release, ENB Therapeutics, NOV 4, 2022, View Source [SID1234634069]).

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Poster Title: ENB-003, an ETBR inhibitor, in combination with pembrolizumab for advanced refractory solid tumors: (Download PDF)

Poster number: 143

Presenter: Sumayah Jamal, MD-PhD

Date: Sunday, November 20, 2022

Location and Time: 4:15 – 6:15 pm in Square Dorchester

About the Summit for Cancer Immunotherapy
Summit4CI 2022 is taking place in Montréal, Quebec, at the Fairmont the Queen Elizabeth. The conference will explore the latest progress in cancer immunotherapy from scientific, clinical, industry and patient perspectives during BioCanRx’s sixth scientific conference. This year’s keynote speaker is Dr. Carl June. To learn more, go to: View Source

About ENB-003
ENB-003 is a selective endothelin B receptor (ETBR) inhibitor that, in preclinical studies, enhanced the efficacy of immunotherapies such as anti-PD-1, anti-CTLA-4 and CAR T across multiple cancer types in preclinical studies. In an ongoing multi-center Phase 1/2 clinical trial, early efficacy signals suggest that ENB-003 overcomes resistance to the anti-PD-1 therapy KEYTRUDA (pembrolizumab) in heavily pre-treated drug resistant cancer patients. The Phase 2 portion of the ENB-003 + pembrolizumab combination study is expected to start in the first quarter of 2023. The trial will enroll melanoma patients with innate resistance to anti-PD-1 based immunotherapies, platinum refractory and platinum resistant ovarian cancer patients, as well pancreatic cancer patients that have failed standard of care.

On November 4, 2022 Oncolys BioPharma reported its Non-consolidated Financial Results for the Nine Months Ended September 30, 2022 (Press release, Oncolys BioPharma, NOV 4, 2022, View Source [SID1234624590]).

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On November 4, 2022 Nerviano Medical Sciences reported A new drug that inhibits an enzyme playing a crucial role in cell division and growth has shown signs of anti-cancer activity with manageable side effects in liver cancer patients who have been treated unsuccessfully previously with up to three lines of treatment (Press release, Nerviano Medical Sciences, NOV 4, 2022, View Source [SID1234623262]).

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Presenting the findings on Friday at the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) [1] Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, Dr Maria Reig, head of the Barcelona Clinic Liver Cancer (BCLC) Unit at Hospital Clinic Barcelona, Barcelona University, Spain, said: "Primary liver cancer is the sixth most common cancer and among the leading causes of cancer-related deaths worldwide. Although new treatments options are becoming available, the overall prognosis for advanced liver cancer remains poor. I wanted to find new treatments for this cancer."

NMS-01940153E has been designed to be a very potent and selective inhibitor of Monopolar Spindle 1 (MPS1), which is a kinase (a type of enzyme) that is overexpressed in several cancers including liver cancer. MPS1 plays a critical role in regulating the processes involved in cell division and growth and, if it malfunctions, it leads to cancer.

Dr Reig said: "Preclinical work demonstrated that NMS-01940153E was highly effective in preventing the proliferation of cancer cells, both on its own and in combination with other anti-cancer drugs. It seems more potent than other kinase inhibitors in liver cancer cells and so we are testing it, as a single agent, in a phase I clinical trial in liver cancer patients."

In a trial called MPS-153-001, NMS-01940153E was given intravenously to 12 patients with liver cancer on days 1, 8 and 15 every four weeks at increasing doses starting at 100mg per metre of body surface area per week (100mg/m2/week). The patients had all had previous treatments with up to three other anti-cancer drugs that eventually failed to halt the cancer.

By 16 August 2022, ten patients had discontinued treatment, seven due to their disease progressing. Out of 11 patients who could be evaluated to see if the drug was making an impact on the cancer, cancer shrank by at least 30% (a partial response) in two of them for 2.5 and 9.3 months. Both discontinued treatment after their cancer started to grow again at 6.5 and 11.1 months, respectively. Two further patients had long-lasting stable disease (the cancer neither grew nor shrank) and are still receiving the treatment after 11 and 18 cycles.

Dr Reig said: "At the 100 mg/m2/w dose, one of six patients who could be evaluated, had a partial response to the study drug. At the 135 mg/m2/w dose, one of five had a partial response. Since each patient had three prior failures with standard treatments, the responses to NMS-01940153E are a strong sign that this new mechanism might be valuable in liver cancer, especially for patients whose cancer has already failed to respond to standard options."

When doses were increased, two patients experienced neutropenia (reduced white blood cell counts) with either sepsis or a urinary tract infection at a dose of 135mg/m2/week – side effects that were serious enough to halt an increase in dosing. Other side effects included abnormally-coloured urine (chromaturia), low platelet counts (thrombocytopenia), anaemia, weakness, diarrhoea, and reaction at the site of the injection, but there was no drug-related death.

"Neutropenia was the main adverse side effect but it was always quickly reversible and mostly managed carefully with observation and dose reductions by the treating physicians," said Dr Reid.

NMS-01940153E is currently being evaluated in a phase II clinical trial in patients with liver cancer that cannot be treated with surgery and whose cancer has failed to respond to the existing standard treatments.

"NMS-01940153E represents a new type of treatment, working in a very different way from the current options for treating liver cancer; therefore, it offers potential to help patients in the future," said Dr Reig. "This is a small study, so the results will need to be shown in larger studies. The strength of the study is that the effect of NMS-01940153E appears to be realistic, due to the history of prior treatment failures of these patients and the early pattern of response we observed. Therefore, these results suggest that NMS-01940153E should continue to be studied in liver cancer and this is happening in the phase II trial, which started in August 2022 and is expected to continue to 2024 at centres in Spain and Italy."

Professor Ruth Plummer, from Newcastle University, UK, is chair of the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium and was not involved with the research. She said: "Drugs to prevent cancer cells dividing and proliferating have not shown much benefit in the clinic for patients with liver cancer so far. Liver cancer is one of the most fatal diseases; the percentage of people with advanced disease who are still alive five years after diagnosis is measured in months rather than years. Therefore, new and more effective treatments are needed urgently. The results from this small study are encouraging and the phase II trial should give us more information about the safety and efficacy of NMS-01940153E."

(ends)

Abstract no: 3LBA, "NMS-01940153E, an MPS1 inhibitor with anti-tumor activity in relapsed or refractory unresectable Hepatocellular carcinoma", by Maria Reig, presented in plenary session 7 ‘Late breaking and proffered papers’, 15.00-16.30 hrs CET on Friday 28 October.

[1] EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR (Free AACR Whitepaper) [American Association for Cancer Research]. The Symposium takes place in Barcelona from 26-28 October 2022.

The study was funded Nerviano Medical Sciences srl.