On June 3, 2022 Experimental Drug Development Centre reported a made-in-Singapore cancer drug, ETC-159, has advanced into the dose expansion portion of its Phase 1B clinical trial (Press release, Experimental Drug Development Centre, JUN 3, 2022, View Source [SID1234654034]). The Phase 1B dose expansion study tests the preliminary efficacy and safety of ETC-159 in a subset of genetically defined patients with microsatellite stable (MSS)1 cancers. MSS tumours have few genetic aberrations and patients are usually unresponsive to immunotherapy like pembrolizumab, a checkpoint inhibitor used in the treatment of many cancers. To date, the first portion of the Phase 1B trial, the dose escalation study, has been completed and a safe dose of ETC-159 in combination with pembrolizumab has been defined. ETC-159 was previously shown to be safe as a monotherapy in its Phase 1A trial.

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ETC-159 was jointly developed by Duke-NUS Medical School (Duke-NUS) and the Experimental Drug Development Centre (EDDC), a national platform for drug discovery and development hosted by the Agency for Science, Technology and Research (A*STAR). This small molecule drug targets a range of solid tumours including colorectal, endometrial, ovarian and pancreatic cancers, which contribute to a significant fraction of Singapore’s cancer burden. A subset of these cancers are caused by hyperactivity in a cell signalling pathway known as the Wnt pathway.

The Phase 1B dose expansion study will have two groups.
In one group, ETC-159 will be tested as a monotherapy in MSS colorectal cancer (CRC) patients who have a specific genetic mutation, called "RSPO Fusion". This mutation is present in about 8% of CRC patients and it activates the Wnt pathway, making these patients sensitive to Wnt inhibitors like ETC-159. A diagnostic test designed by EDDC was manufactured and clinically validated at POLARIS @ A*STAR’s Genome Institute of Singapore (GIS). Supported by the Diagnostics Development (DxD) Hub, this test will be used to select colorectal cancer patients with RSPO Fusion to participate in the trial. RNA Extraction from Formalin-Fixed Paraffin-Embedded (FFPE)2 tissue samples followed by testing of Fusion genes will be done at POLARIS @ GIS.

In the second dose expansion patient group, ETC-159 will be tested in combination with the immune checkpoint inhibitor pembrolizumab in MSS colorectal cancer patients who do not have RSPO fusions, as well as in patients with MSS endometrial and MSS ovarian cancers. The ability of ETC-159 to sensitise MSS cancers to pembrolizumab will be investigated. The combination of ETC-159 and pembrolizumab has been demonstrated to be synergistic in preclinical studies.

As in earlier trials, investigators will track the biological effect of ETC-159, also known as its pharmacodynamics, in patients participating in the dose expansion study. The pharmacodynamics of a drug can be measured from tumour samples taken through biopsies, such as during surgery or an invasive procedure. EDDC established that it will also be possible to measure the pharmacodynamics of the drug through monitoring the levels of Axin2 mRNA in hair follicles. Axin2 is a downstream protein in the Wnt pathway, and its levels are reduced when ETC-159 effectively acts on the pathway. This minimally invasive measurement of ETC-159’s biological effect will allow investigators to understand how well the drug is working in patients over the course of study.

Patients for the dose expansion study will come from two sites in Singapore as well as seven sites in the United States. The trial is expected to be completed by 2024.

On June 3, 2022 Novartis reported results of an exploratory retrospective biomarker analysis finding that different genetic mutation profiles in tumors harboring PIK3CA mutation did not affect treatment benefit with Piqray (alpelisib) plus fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer following progression on or after an endocrine-based regimen (Press release, Novartis, JUN 3, 2022, View Source [SID1234634694]). Selected as an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #1006), the retrospective analysis of data from the Phase III SOLAR-1 study found that the clinical benefit of the Piqray and fulvestrant combination was maintained regardless of genetic alterations in most biomarkers, including ESR1 and genes implicated in resistance to CDK4/6 inhibitors1.

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"This analysis evaluating alpelisib and fulvestrant across HR+/HER2- advanced breast cancer tumors with different genetic alterations confirms the importance of using alpelisib to selectively target PIK3CA as a major oncogenic driver in these tumors," said Dejan Juric, MD, Director, Termeer Center for Target Therapies, Mass General Cancer Center in Boston.

"PIK3CA mutations affect approximately 40% of those with the HR+/HER2- subtype and are known oncogenic drivers of metastatic breast cancer, associated with endocrine resistance and an overall worse prognosis—so it’s critical for physicians to test and treat with Piqray for patients with PIK3CA mutations upfront consistent with ASCO (Free ASCO Whitepaper) and NCCN guidelines," said Reshema Kemps-Polanco, Executive Vice President, US Oncology at Novartis.

Highlights from the SOLAR-1 biomarker retrospective analysis at ASCO (Free ASCO Whitepaper)

Patients with ESR1 gene alterations achieved 12.0 months of median progression-free survival (mPFS) when treated with Piqray and fulvestrant compared to 6.5 months for those treated with fulvestrant alone1.
Even patients with FGFR1 and FGFR2 gene alterations, which have been associated with resistance to CDK4/6 inhibitors, had benefit when treated with Piqray plus fulvestrant (12.7 months and 9.6 months mPFS, respectively), compared to those treated with fulvestrant alone (3.8 months and 2.8 months mPFS, respectively)1.
The benefit seen with the Piqray and fulvestrant combination was independent of additional genetic alterations, including TP53, CCND1, MAP3K1 and ARID1A; genes in the MAPK pathway, genes implicated in CDK4/6 inhibitor resistance such as RB11.
Real-world evidence supports effectiveness of Piqray in tumors with PIK3CA mutation
A real-world retrospective analysis (Abstract #1055) showed clinical benefit for 157 patients with HR+/HER2- advanced or metastatic breast cancer with PIK3CA genetic mutation following treatment with Piqray plus fulvestrant, even when exposed to prior treatment with fulvestrant, confirming the oncogenic dependence of the tumor on the PIK3CA mutation2. In the analysis, prior fulvestrant treatment included CDK4/6 inhibior plus fulvestrant (74.5%), fulvestrant alone (33.8%), and non-CDK4/6 inhibitor plus fulvestrant (21.0%)2.

About PIK3CA-mutated Breast Cancer
An estimated 361,826 people are diagnosed with metastatic breast cancer worldwide each year, and approximately 40% of those with HR+/HER2- subtype have tumors that harbor a PIK3CA mutation, which is associated with a poor prognosis6-7.

About Piqray (alpelisib)
Piqray is a kinase inhibitor developed for use in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after endocrine-based regimen3. Piqray is approved in over 70 countries, including the US6. In the European member states, Piqray plus fulvestrant is approved after disease progression following endocrine therapy as monotherapy8.

Novartis is continuing to reimagine cancer with additional trials of Piqray. To complement the SOLAR-1 study, EPIK-B5, a large Phase III clinical trial is conducted with Piqray in combination with fulvestrant following treatment with a CDK4/6 inhibitor and aromatase inhibitor9. Novartis is also studying the potential of Piqray in triple-negative breast cancer (TNBC) in the EPIK-B3 Phase III clinical trial, in advanced HER2+ breast cancer in the EPIK-B2 Phase III clinical trial and in ovarian cancer in the EPIK-O Phase III clinical trial10-12.

On June 3, 2022 Helix BioPharma Corp. (TSX: "HBP") ("Helix" or the "Company"), a clinical-stage biopharmaceutical company developing unique therapies in the field of immuno-oncology, based on its proprietary technological platform DOS47, reported that it has successfully closed its Early Warrant Exercise Incentive Program (the "Incentive Program") and Extension of Warrant Exercise Period ("Warrant Extension"), previously announced on March 11, 2022 and April 13, 2022 (Press release, Helix BioPharma, JUN 3, 2022, View Source [SID1234615761]). The Company has received gross proceeds of $3,210,204 from the exercise of 12,346,938 share purchase warrants at $0.26 per share.

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The balance of the warrants not exercised under this Incentive Program and Warrant Extension will remain outstanding and continue to be exercisable for common shares of the Company on their original terms.

The proceeds from the Incentive Program and Warrant Extension will be used for working capital purposes and advancing the Company’s L-DOS47 drug development program.

Artur Gabor, CEO of Helix, stated "We are extremely grateful for the support and belief in the Company from the warrant holders that participated in our Early Warrant Exercise Incentive Program and Warrant Extension. This is significant as it demonstrates their belief in the Company and the technology. With the capital raised, we are financially well situated for operations for our development programs."

On June 3, 2022 Caris Life Sciences (Caris), the leading molecular science and technology company actively developing and delivering innovative solutions to revolutionize healthcare, reported its Caris Assure liquid biopsy assay at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Booth #22081) (Press release, Caris Life Sciences, JUN 3, 2022, View Source [SID1234615604]).

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"Caris Assure establishes a new standard for liquid biopsy testing," said David D. Halbert, Chairman, Founder and CEO of Caris Life Sciences. "Current liquid biopsy offerings examine smaller panels of genes, which lack the versatility for the identification of novel predictive markers and signatures that are only possible through the whole exome and whole transcriptome approach unique to Caris. With Caris Assure, we have created the most extensive sequencing assay available to ensure we leave no stone unturned in properly guiding treatment selection and ongoing cancer care management."

Caris Assure is a blood-based molecular profiling assay that uses a novel circulating nucleic acids sequencing (cNAS) approach to analyze the Whole Exome (cfDNA) and Whole Transcriptome (cfRNA) of 22,000 genes, including Loss of Heterozygosity (LOH), Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) from a simple blood sample. This unique assay includes characterization of somatic tumor alterations, somatic Clonal Hematopoiesis of Indeterminate Potential (CHIP) alterations and identification of incidental germline findings. The assay further enables minimally invasive serial monitoring for detection of tumor heterogeneity and emergence of resistance mutations.

"We have applied the same industry leading, multi-cancer profiling technology used in our tissue assay to blood," said David Spetzler, M.S., Ph.D., MBA, President and Chief Scientific Officer of Caris. "Our broad, 22,000 gene WES and WTS analysis ensures we render the most accurate results and findings for physicians seeking to properly diagnose, treat and monitor cancer patients. We are excited to bring this assay to the market and provide physicians with a new and comprehensive multi-cancer blood assay to add to their cancer diagnoses and treatment strategies."

Caris Assure sequences the largest panel of genes across both cfDNA (Whole Exome) and cfRNA (Whole Transcriptome), which helps overcome many of the shedding problems that plague cfDNA-only assays. By including DNA and RNA coverage across somatic tumor, somatic CHIP and germline alterations, Caris Assure captures more tumor-informed material, leading to improved performance and comprehensive molecular profiling results for the physician and patient. The approach also results in fewer missed mutations due to more tumor derived material inputs and concordance to tissue, as well as fewer false positives due to the analysis of CHIP mutations.

In an initial performance validation study of this first-of-its-kind whole exome, whole transcriptome (22,000 gene) blood assay, Caris Assure demonstrated more than 95 percent sensitivity for variant frequencies greater than 0.5 percent, while maintaining greater than 99.99 percent specificity. Additional validation data will be released in the coming months.

Caris Assure will be commercially available in the second half of calendar year 2022, with limited availability in the third quarter and expanding availability in Q4 and 2023.

On June 3, 2022 Patrys reported that share news that the Telethon Kids Institute has been awarded significant funding from the Cure Brain Cancer Foundation to support research for Patrys’ PAT-DX1 and PAT-DX3 programs (Press release, Patrys, JUN 3, 2022, View Source [SID1234615602]).

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The grant will be used to investigate Patrys’ deoxymab assets PAT-DX1 and PAT-DX3 in both in vitro and in vivo studies of high grade glioma (HGG), by combining with standard of care (SOC) treatments such as radiotherapy and temozolomide to determine efficacy.

Based within the Perth Children’s Hospital, the Telethon Kids Institute conducts translational research focused on improving treatments for the health and wellbeing of children. The research will be led by Professor Terrance Johns, who is at the forefront of Australian brain cancer research.

Patrys CEO and Managing Director, Dr James Campbell, said:

"This is one of our most exciting collaborations to date. Professor Terrance Johns and his team are pivotal in the brain cancer space in Australia. We gratefully acknowledge the Cure Brain Cancer Foundation Clinical Accelerator grant scheme for providing funding for therapeutic products with the potential to improve the pathway to the clinic."