On August 25, 2021 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or the "Company"), an Australian-based clinical stage radiopharmaceutical company developing next-generation products to address the growing need in oncology, reported that the first US patient has been dosed with 64Cu SAR-bisPSMA in the dosimetry phase of the SECuRE clinical trial (NCT04868604)[1] investigating Targeted Copper Theranostics (TCTs) in patients with metastatic castrate resistant prostate cancer (mCRPC) at the Urology Cancer Center and GU Research Network in Omaha, Nebraska (Press release, Clarity Pharmaceuticals, AUG 25, 2021, View Source [SID1234586895]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are very excited to have treated our first US patient in the SECuRE trial for mCRPC using our optimised PSMA agent, 64/67Cu SAR-bisPSMA, and look forward to recruiting additional patients and opening all seven clinical sites selected for this trial in the US. We believe the central manufacture, logistical and treatment advantages of TCTs using copper-64 and copper-67 in large patient populations such as prostate cancer will benefit both clinicians and patients.

The SECuRE trial is a Phase I/IIa theranostic trial for identification and treatment of PSMA-expressing mCRPC using TCT. 64Cu SAR-bisPSMA is used to image and select patients for 67Cu SAR-bisPSMA therapy. The initial dosimetry phase utilises 64Cu SAR-bisPSMA to determine biodistribution and dosimetry over multiple time points. The entire trial is a multi-centre, single arm, dose escalation study with a cohort expansion planned for up to 44 patients in the US. The aim of this trial is to determine the safety and efficacy of 67Cu-SAR-bisPSMA as a therapy.

Dr Luke Nordquist, CEO, Urologic Medical Oncologist at the Urology Cancer Center and GU Research Network in Omaha, Nebraska, who treated the first patient with 64Cu SAR-bisPSMA in the trial, commented on this milestone, "64/67Cu SAR-bisPSMA products hold great promise of improving prostate cancer diagnosis and treatment and have the potential to provide significant supply benefits in comparison to current products in the market. We look forward to working together with Clarity to explore these benefits and utilise them to improve the lives of men with this insidious disease."

Dr Taylor said: "The prostate cancer market is a key focus for Clarity. The news of the SECuRE trial recruitment milestone comes shortly after treating our first patient in the PROPELLER trial, a diagnostic 64Cu SAR-bisPSMA clinical trial in patients with confirmed prostate cancer (NCT04839367)[2]. We are excited to now have two clinical trials in prostate cancer actively recruiting and treating patients and to build on the compelling results from our therapeutic and diagnostic preclinical studies. We look forward to progressing these trials and getting closer to achieving our ultimate goal of developing better treatments for children and adults with cancer."

About Prostate Cancer

Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide[3]. In 2021, the National Cancer Institute estimated 248,530 new cases of prostate cancer in the US and around 34,130 deaths from the disease[4]. Annually, there are around ~34,000 men in the US who are diagnosed with mCRCP[5], ~90% of whom have tumours which express PSMA[6].

References

[1]. ClinicalTrials.gov Identifier: NCT04868604 View Source
[2]. ClinicalTrials.gov Identifier: NCT04839367 View Source
[3]. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries View Source
[4]. American Cancer Society, Cancer Statistics Center,
View Source!/cancer-site/Prostate
[5]. American Cancer Society, Cancer Statistics Center,
View Source!/cancer-site/Prostate
[6]. D. A. Silver, I. Pellicer, W. R. Fair, W. D. Heston and C. Cordon-Cardo 1997. "Prostate-specific membrane antigen expression in normal and malignant human tissues." Clinical Cancer Research. vol. 3, 81-85, January 1997

This announcement has been authorised for release by the Board.

On August 25, 2021 Thermo Fisher Scientifi reported that The U.S. Food and Drug Administration (FDA) has granted pre-market approval to Oncomine Dx Target Test as a companion diagnostic (CDx) to identify patients with isocitrate dehydrogenase-1 (IDH1) mutated cholangiocarcinoma (CCA) who may be candidates for Servier Pharmaceuticals’ TIBSOVO (ivosidenib tablets) (Press release, Thermo Fisher Scientific, AUG 25, 2021, View Source [SID1234586894]). TIBSOVO is an IDH1 inhibitor that is approved for the treatment of adult patients with previously treated, locally advanced or metastatic CCA with an IDH1 mutation as detected by an FDA-approved test.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CCA is a rare, aggressive cancer of the bile ducts within and outside of the liver. IDH1 mutations occur in up to 20 percent of CCA cases in the Unites States and are not associated with prognosis.1 Prior to the approval of TIBSOVO on August 25, 2021, there were no approved targeted therapies for IDH1-mutated cholangiocarcinoma and limited chemotherapy options are available in the advanced setting.2

TIBSOVO is also approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutated relapsed or refractory acute myeloid leukemia (AML) and for adults with newly diagnosed IDH1-mutated AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. The approval of TIBSOVO in previously treated IDH1-mutated CCA is supported by data from the ClarIDHy study, the first and only randomized Phase 3 trial for previously treated IDH1-mutated CCA.

"Prior to today, patients with IDH1-mutated cholangiocarcinoma did not have an approved targeted therapy treatment option," said Susan Pandya, M.D., vice president, clinical development, head of cancer metabolism global development, Servier Pharmaceuticals. "The FDA approval of TIBSOVO (ivosidenib tablets) for patients with previously treated IDH1-mutated cholangiocarcinoma is a major milestone for the cholangiocarcinoma community. I’d like to acknowledge and thank all the patients, their families and the investigators and research teams who took part in the ClarIDHy study, as well as Thermo Fisher Scientific for their partnership."

The Oncomine Dx Target Test is a next-generation sequencing (NGS) based test that delivers robust and reproducible results in the IDH1 gene clinically associated with CCA. The FDA first approved the test as a CDx in 2017, and it is now approved for four targeted therapies for non-small cell lung cancer (NSCLC) and one targeted therapy for CCA in the U.S. The test is currently approved and reimbursed by government and commercial insurers in over 15 countries, including U.S., Europe, Japan, South Korea and the Middle East, covering more than 550 million lives globally.

"With the FDA approval of Oncomine Dx Target Test as a companion diagnostic for TIBSOVO, healthcare providers across the U.S. can now match patients with this critically needed therapy," said Garret Hampton, president of clinical next-generation sequencing and oncology at Thermo Fisher Scientific. "Advances in genetic profiling through NGS have enabled identification of an increasing number of cancer-driving genomic variations, opening the door for the development of more targeted treatment options. By continuing to work with our pharmaceutical partners to co-develop diagnostics for these life-changing therapies and expanding the clinical utility of our tests, we hope to help more cancer patients around the world receive more targeted and effective treatment."

Thermo Fisher also has an agreement with Servier to develop and commercialize a CDx leveraging the Oncomine Precision Assay* to identify low-grade glioma (LGG) patients with isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations who may be eligible for vorasidenib (AG-881). The Oncomine Precision Assay runs on the Ion Torrent Genexus* System, the first fully integrated NGS platform featuring an automated specimen-to-report workflow that delivers results economically in a single day.

*This assay and instrument are currently For Research Use Only. Not for use in diagnostic procedures.

On August 25, 2021 Servier Pharmaceuticals, a growing leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported that the U.S. Food and Drug Administration (FDA) approved TIBSOVO (ivosidenib tablets) for the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation as detected by an FDA-approved test (Press release, Servier, AUG 25, 2021, View Source [SID1234586893]). TIBSOVO is the first and only targeted therapy approved for patients with previously treated IDH1-mutated cholangiocarcinoma.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The supplemental New Drug Application (sNDA) for TIBSOVO received Priority Review, which accelerated the review timeline and is typically given to drugs that may offer major advances in treatment or may provide a treatment where no adequate therapy exists.

"Servier has been focused on exploring the significant potential of inhibiting mutant IDH enzymes as a novel approach to treating cancers with high unmet needs, including cholangiocarcinoma," said David K. Lee, CEO, Servier Pharmaceuticals. "We are proud to bring to patients the first and only targeted therapy for previously treated IDH1-mutated cholangiocarcinoma. We are grateful to the patients, caregivers, investigators and study teams who made this achievement possible through their participation in the ClarIDHy clinical trial."

The FDA approval of this indication is supported by data from the ClarIDHy study, the first and only randomized Phase 3 trial for previously treated IDH1-mutated cholangiocarcinoma. Results from the ClarIDHy study demonstrated a statistically significant improvement in the primary endpoint of progression-free survival (PFS) by an independent review committee (hazard ratio [HR] 0.37; 95% CI [0.25, 0.54], p<0.001).1 The median PFS (95% CI) for TIBSOVO and placebo was 2.7 (1.6, 4.2) and 1.4 (1.4, 1.6) months, respectively. Thirty-two percent and 22% of patients randomized to TIBSOVO remained free of progression or death at 6 and 12 months, respectively, versus none on the placebo arm.

The study protocol specified that patients randomized to placebo could cross over to TIBSOVO at the time of disease progression, and a high proportion of patients in the placebo arm (70.5%) crossed over to TIBSOVO. The study also showed the key secondary endpoint of overall survival (OS) favoring patients randomized to TIBSOVO compared to those randomized to placebo; however, statistical significance was not reached.1 OS results are based on the final analysis of OS (based on 150 events which occurred 16 months after the final analysis of PFS. The median OS (95% CI) for TIBSOVO was 10.3 (7.8, 12.4) months; and placebo was 7.5 (4.8, 11.1) months without adjusting for crossover.

The safety profile observed in the study was consistent with previously published data.1 The most common adverse reactions (≥15%) in patients with cholangiocarcinoma were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash.

The recommended TIBSOVO dosage for previously treated IDH1-mutated cholangiocarcinoma is 500 mg orally once daily with or without food until disease progression or unacceptable toxicity.

"Patients living with IDH1-mutated cholangiocarcinoma, especially those whose disease progresses following chemotherapy, are in urgent need of new treatment options," said Rachna T. Shroff, MD, Associate Professor of Medicine, University of Arizona, and Chief of GI Medical Oncology at the University of Arizona Cancer Center. "In addition to an acceptable safety profile, TIBSOVO demonstrated an impressive, significant benefit in progression-free survival, underscoring its importance as a new option for patients battling this aggressive cancer."

Cholangiocarcinoma is a rare, aggressive cancer of the bile ducts within and outside of the liver. An estimated 8,000 people in the United States are diagnosed with cholangiocarcinoma each year. However, the actual number of these cases is likely to be higher, as cholangiocarcinoma can be hard to diagnose, and may be misclassified as other types of cancer.2

"Before today’s approval of TIBSOVO, there were no approved targeted therapies available to cholangiocarcinoma patients harboring the IDH1 mutation, and limited chemotherapy options available to patients with advanced disease," said Stacie Lindsey, Founder and CEO, Cholangiocarcinoma Foundation. "This approval brings new hope to the cholangiocarcinoma community and we are excited that this much-needed new therapeutic option is being made available to patients."

Servier Pharmaceuticals is introducing ServierONE Patient Support Services, a program that offers one-on-one support to help patients who are prescribed TIBSOVO or other Servier products navigate their cancer journey. Eligible patients will have access to financial assistance, emotional support and other resources. More information can be found at www.servierone.com.

TIBSOVO* is also approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutated relapsed or refractory acute myeloid leukemia (AML) and for adults with newly diagnosed IDH1-mutated AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy.

About Cholangiocarcinoma

Cholangiocarcinoma is a rare, aggressive cancer of the bile ducts within and outside of the liver. IDH1 mutations occur in up to 20% of cholangiocarcinoma cases in the U.S. and are not associated with prognosis.3 Prior to the approval of TIBSOVO, there were no approved targeted therapies for IDH1-mutated cholangiocarcinoma and limited chemotherapy options are available in the advanced setting. Gemcitabine-based chemotherapy is often recommended for newly diagnosed advanced or metastatic disease.

On August 25, 2021 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported two oral presentations of clinical data will be presented at the upcoming European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) 2021, reinforcing the clinical benefit of adagrasib, a KRASG12C inhibitor, and sitravatinib, a receptor tyrosine kinase inhibitor (Press release, Mirati, AUG 25, 2021, View Source [SID1234586892]). The congress will take place virtually from September 16 to 21, 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Mirati continues to make important progress in demonstrating the clinical impact our investigational treatments may have on patient outcomes in lung and colorectal cancers," said Charles M. Baum, M.D., Ph.D., president and chief executive officer, Mirati Therapeutics, Inc. "The data we are presenting at ESMO (Free ESMO Whitepaper) will show how adagrasib alone and in combination with cetuximab offer encouraging clinical activity in patients with KRASG12C-mutated colorectal cancer. In addition, updated survival data from our Phase 2 study evaluating sitravatinib with nivolumab supports the potential of this combination for patients with advanced lung cancer whose tumors are resistant to checkpoint inhibitors."

Dr. Baum added, "We are investigating several combination approaches in our expanding pipeline with the goal of improving standards of care and the course of treatment for people with cancer. We are thankful to the investigators and patients, without whom our research would not be possible."

Learn more about Mirati’s development of therapies that target the genetic and immunological drivers of cancers at Mirati.com/science.

Mirati studies at ESMO (Free ESMO Whitepaper) Congress 2021 include:
*All times noted are Central European Summer Time (CEST)

Presentation Title: KRYSTAL-1: Adagrasib (MRTX849) as Monotherapy or Combined with Cetuximab in Patients With Colorectal Cancer Harboring a KRASG12C Mutation
Author: Jared Weiss
Abstract Number: LBA6
Session: Presidential Symposium II
Presentation Date/Time: Sunday, September 19, 2021 at 15:47-16:02 CEST | Channel 1

Presentation Title: MRTX-500: Phase 2 Trial of Sitravatinib (Sitra) + Nivolumab (Nivo) in Patients (Pts) With Nonsquamous (NSQ) Non–Small-Cell Lung Cancer (NSCLC) Progressing on or After Prior Checkpoint Inhibitor (CPI) Therapy
Author: Ticiana A. Leal
Abstract Number: 1191O
Session: NSCLC Proffered Paper Session II
Presentation Date/Time: Monday, September 20, 2021 at 14:10-14:20 CEST | Channel 4

About Adagrasib (MRTX849)

Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C mutated cancers, as the KRASG12C protein regenerates every 24-48 hours. Studies of adagrasib have shown that the drug has a long half-life, extensive tissue distribution and is well tolerated. Adagrasib has also shown single-agent responses in non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, and other solid tumors with KRASG12C mutations. Adagrasib is a being evaluated in several clinical trials in combination with other anti-cancer therapies with strong scientific rationale in patients with advanced solid tumors. Registration-enabling studies are ongoing in NSCLC and colorectal cancer. For more information visit Mirati.com/science.

About Sitravatinib

Sitravatinib is an investigational spectrum-selective kinase inhibitor that potently inhibits receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, Mer), split family receptors (VEGFR2, KIT) and RET. Sitravatinib is being evaluated in combination with nivolumab (OPDIVO), an anti-PD-1 checkpoint inhibitor, in patients whose cancers have progressed despite treatment with a checkpoint inhibitor. Sitravatinib’s potent inhibition of TAM and split family RTKs may overcome resistance to checkpoint inhibitor therapy through targeted reversal of an immunosuppressive tumor microenvironment, enhancing antigen-specific T cell response and expanding dendritic cell-dependent antigen presentation. Sitravatinib is being evaluated in multiple clinical trials to treat patients who are resistant to prior immune checkpoint inhibitor therapy and progressed on platinum doublet therapy, including the ongoing potentially registration-enabling Phase 3 trial of sitravatinib in combinations with a checkpoint inhibitor in non-small cell lung cancer (NSCLC). In addition, sitravatinib in combinations with checkpoint inhibitors are being evaluated in selected checkpoint inhibitor naïve patients.

On August 25, 2021 NovaRock Biotherapeutics Limited, a clinical-stage biopharmaceutical company delivering innovative specialty pharmaceuticals to address patients’ unmet medical needs, reported that they have entered into an exclusive license agreement and strategic partnership with Flame Biosciences (Press release, NovaRock Biotherapeutics, AUG 25, 2021, View Source [SID1234586891]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are very pleased to be partnering with Flame and their world-class clinical team," said Dr. Han Li, CEO of NovaRock. "The collaboration with Flame marks a solid step towards getting NovaRock’s innovative portfolio into the global market. The proceeds from this collaboration will be primarily used to fund the clinical advancement of NBL-012 and NBL-015 as well as the advancement of our preclinical programs."

NBL-015 is a fully human anti-Claudin 18.2 monoclonal antibody optimized through protein engineering to achieve enhanced ADCC, CDC, and ADCP effects. Its Investigational New Drug Application has also been approved by the U.S. FDA in May 2021.

Under the terms of the Agreement, NovaRock has granted Flame Biosciences the exclusive rights to NBL-015 outside of Greater China (including mainland China, Hong Kong, Macau, and Taiwan). Flame shall be responsible for the development, regulatory approval, and commercialization of NBL-015. NovaRock will, at Flame Biosciences’s expense, collaborate with Flame on the discovery and preclinical development of two new bispecific antibodies based on NovaRock’s NovaTE bi-specific antibody technology platform and subsequently grant Flame Biosciences the exclusive rights to further develop, manufacture and commercialize the Licensed Products. The lead product candidates from this collaboration are expected to enter clinical development in late 2023.

NovaRock will receive an upfront payment of US$7.5 million and is eligible to receive development milestone payments of up to US$172.5 million subject to achievement of the development milestone events. NovaRock is also eligible to receive sales milestone payments of up to US$460 million subject to the achievement of the sales milestone events and royalties based on a certain percentage of the net sales of the Licensed Products in the Territory.

About NBL-015

NBL-015 is a fully human anti-Claudin 18.2 monoclonal antibody optimized through protein engineering to achieve enhanced ADCC, CDC, and ADCP effects. Preclinical studies have demonstrated that NBL-015 has significant advantages over similar drugs in terms of low immunogenicity, good safety, high affinity, and high anti-tumor activity, providing a promising prospect of becoming the best-in-class target therapy to treat pancreatic and gastric cancer. NBL-015 has been granted the orphan-drug designation for the treatment of pancreatic cancer and gastric cancer, including cancer of gastroesophageal junction by the U.S. Food and Drug Administration (FDA). Its Investigational New Drug Application (IND) has also been approved by the U.S. FDA in May 2021.

About NovaTE bi-specific antibody technology platform

NovaTE is a novel tumor antigen and CD-137 bispecific antibody technology platform that is designed to selectively activate the antigen-experienced T cells in the tumor microenvironment. Its proprietary scaffold can maximize the tumor cell engaging and T cell activation while minimizing the systematic adverse events. Antibodies developed using NovaTE have demonstrated superior efficacy and safety in preclinical studies. Moreover, the unique bi-specific antibody structure offers exceptional stability and manufacturability.