On June 6, 2022 Senhwa Biosciences, Inc. (TPEx: 6492), a drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and novel coronaviruses, reported that it has received written approval from the Human Research Ethics Committee (HREC), Australia to begin a Phase I study evaluating Senhwa’s Pidnarulex, the 2019 PCF-Pfizer Global Challenge Awards winner will be used in combination with Pfizer’s PARP inhibitor, Talazoparib (Talzenna), to explore potential therapy in patients with metastatic The study will be conducted by Peter MacCallum Cancer Centre (PMCC), Senhwa’s clinical partner in Melbourne, Australia (Press release, Senhwa Biosciences, JUN 6, 2022, View Source [SID1234615671]).

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This Phase I trial of Pidnarulex and Talazoparib will be mainly funded by the US Prostate Cancer Foundation (PCF) and Pfizer. Senhwa will provide supplies of their study drug, Pidnarulex, in addition to some specific funding for the study.

Pfizer’s Talazoparib, an oral PARP inhibitor (PARPi), received FDA’s approval in October 2018 for the treatment of adults with deleterious or suspected deleterious germline BRCA mutation–positive, HER2-negative locally advanced or metastatic breast cancer. While BRCA1/2 deficient tumor cells are responsive to PARPi treatments, the development of PARPi resistance is common.

In the previous Phase I trial conducted by CCTG, Senhwa’s Pidnarulex demonstrated clinically significant and persist benefits in patients with specific tumor biomarkers, such as BRCA1/2, and PALB2 mutations, and who had been exposed to platinum and other chemotherapeutics.

"Pidnarulex, alone, has shown efficacy in tumor cells resistant to PARPi in the preclinical studies. Therefore, we think Pidnarulex demonstrates great potential as an alternative treatment for prostate cancer patients who have acquired resistance to PARPi or other chemotherapies," said Dr. John Soong, Chief Medical Officer of Senhwa Biosciences.

Prostate Cancer is the second most lethal cancer for men in the United States. Although nearly 70% of patients can be cured with surgery, once the cancer has metastasized, almost all patients develop into castration-resistance, with a median survival time of less than two years.

About Pidanrulex (CX-5461)

Specific mutations within the Homologous Recombination (HR) pathway may be exploited by Pidnarulex through a synthetic lethality approach by targeting the DNA repair defects in Homologous Recombination Deficiency (HRD) tumors. Specifically, Pidnarulex is designed to stabilize DNA G-quadruplexes of cancer cells which leads to disruption of the cell’s replication fork. While acting in concert with HR pathway deficiencies, such as BRCA1/2 mutations, replication forks stall and cause DNA breaks, ultimately resulting in cancer cell death.

On June 6, 2022 Shanghai Henlius Biotech, Inc. (2696.HK) reported that an international randomized phase 3 study (ASTRUM-005) of HANSIZHUANG (serplulimab), an anti-PD-1 mAb independently developed by Henlius, as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC) has been orally presented at 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Shanghai Henlius Biotech, JUN 6, 2022, View Source [SID1234615670]). Serplulimab is the first China-developed anti-PD-1 mAb in first-line treatment of lung cancer that was presented orally at ASCO (Free ASCO Whitepaper) Annual Meeting. The leading principal investigator is Professor Ying Cheng from Jilin Cancer Hospital.

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Professor Ying Cheng said, "ASTRUM-005 is the first and largest ES-SCLC international multi-center clinical study led by Chinese researchers for anti-PD-1 mAb. A total of 114 sites’ subjects were screened around the globe, with 31.5% being Caucasian. The study results demonstrated that serplulimab in combination with chemotherapy can significantly extend the median OS to 15.4 months when compared to the control group in first-line SCLC, gaining global recognition while leapfrogging immunotherapy treatment for SCLC patients."

Mr. Jason Zhu, President of Henlius, said, "HANSIZHUANG is an innovative mAb independently developed by Henlius. Based on the large number of unmet clinical needs, the company has implemented a comprehensive first-line treatment strategy for lung cancer with multiple clinical trials. Previously, the NDA of HANSIZHUANG for the treatment of ES-SCLC has been accepted by NMPA, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. We are hoping that the approval comes soon to mend the gap and bring a new treatment option to patients living with ES-SCLC. Going forward, we will proactively promote more clinical research, thereby benefiting more patients around the world."

ASTRUM-005 has set up a total of 128 sites in China, Turkey, Poland, Georgia, etc. and enrolled 585 subjects from 114 sites, among whom 31.5% were Caucasian. In December 2021, ASTRUM-005 met its primary study endpoint of the overall survival (OS) in the interim analysis and demonstrated HANSIZHUANG with a manageable safety profile. The global clinical data lays a solid foundation for future applications across the world. ASTRUM-005 results are as follows:

Title

Serplulimab, a novel anti-PD-1 antibody, plus chemotherapy versus chemotherapy alone as first-line treatment for extensive-stage small-cell lung cancer: An international randomized phase 3 study (Abstract No. 8505)

Study design

This randomized, double-blind, international, multicenter, phase 3 clinical study aimed to compare the efficacy and safety of serplulimab with placebo when combined with chemotherapy (carboplatin-etoposide) in previously untreated patients with ES-SCLC. Enrolled patients were randomized 2:1 to receive intravenous infusion of either serplulimab or placebo in combination with chemotherapy every three weeks until disease progression, death, intolerable toxicity, withdrawal of informed consent or other reasons specified in the protocol (whichever occurred first). The primary endpoint of this study was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), safety, pharmacokinetic characteristics, and immunogenicity.

Results

As of October 22, 2021, 585 eligible patients were randomized (serplulimab group, n=389; placebo group, n=196), with a median follow-up duration of 12.3 months. The median OS in the serplulimab group and the placebo group were 15.4 (95% CI 13.3–NE) and 10.9 (95% CI 10.0–14.3) months, respectively, with a hazard ratio (HR) of 0.63 (95% CI 0.49–0.82; p<0.001). The 24-month OS rate in the two treatment groups were 43.1% and 7.9%, respectively. Median PFS assessed by the independent radiology review committee (IRRC) per RECIST v1.1 was 5.7 months in the serplulimab group and 4.3 months in the placebo group (HR 0.48, 95% CI 0.38–0.59). Efficacy improvements were also observed in ORR (80.2% vs. 70.4%) and DOR (median, 5.6 vs. 3.2 months) as assessed by IRRC per RECIST v1.1.

Grade ≥3 treatment related adverse events (TRAEs) related to serplulimab or placebo were reported by 129 (33.2%) and 54 (27.6%) patients in the respective groups. Incidence of immune-related adverse events (irAEs) was higher in the serplulimab group compared to the placebo group (37.0% vs. 18.4%), and was similar to the approved PD-1/PD-L1 antibodies.

Conclusions

The results demonstrated that serplulimab in combination with carboplatin-etoposide significantly improved OS as first-line treatment in ES-SCLC patients. The safety profile was consistent with previous studies. Serplulimab, as the first anti-PD-1 antibody showing OS benefit in untreated ES-SCLC patients, possess the potential to provide an alternative treatment option for this patient population worldwide.

About HANSIZHUANG

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. Up to date, 1 indication is approved for marketing in China, 2 NDAs have been accepted by the NMPA, and 9 clinical trials are ongoing across the world.

HANSIZHUANG was approved by the NMPA for the treatment of MSI-H solid tumors in March 2022 and actively promotes its synergy with in-house products of the company and innovative therapies. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 9 clinical trials on immuno-oncology combination therapies worldwide in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. As of now, the company has enrolled more than 2,800 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of Caucasian is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDAs of the treatment for squamous non-small cell lung cancer (sqNSCLC) and the first-line treatment of extensive small-cell lung cancer (ES-SCLC) have been accepted by the NMPA. Furthermore, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) for the treatment of ES-SCLC and was also granted orphan drug designation by the FDA for treatment of SCLC. The MAA of ES-SCLC is expected to be filed in the EU in 2022, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. In the field of esophageal squamous cell carcinoma, the phase 3 clinical trial of HANSIZHUANG in combination with chemotherapy has met the co-primary endpoints.

On June 6, 2022 The Menarini Group ("Menarini") and Radius Health, Inc. ("Radius") (NASDAQ: RDUS) (collectively, the "Companies") reported the presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting of data from the EMERALD phase 3 clinical trial (NCT03778931) (Press release, Menarini, JUN 6, 2022, View Source [SID1234615669]). In a non-pre-specified subgroup analysis of patients with ER+/HER2− metastatic breast cancer (mBC) without prior chemotherapy in the metastatic setting, elacestrant significantly prolonged progression-free survival (PFS) compared to standard of care (SOC) endocrine therapy.

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EMERALD study met both of its pre-specified primary end points of progression-free survival (PFS) in the overall population and in patients with ESR1 mutation (mESR1).1

77.8% (n=371) out of the 477 patients enrolled in the trial had not received prior chemotherapy in the metastatic setting for ER+/HER2−mBC. Among these patients, elacestrant showed the following results compared to SOC:
– 31% reduction in the risk of progression or death in all patients (HR=0.681 [95% CI: 0.520 – 0.891]; P=0.00388) and prolonged median PFS (3.68 vs 1.97 months).
– 46% reduction in the risk of progression or death in patients with mESR1 (HR=0.535 [95% CI: 0.356 – 0.799]; P=0.00235) and prolonged median PFS (5.32 vs 1.91 months).

At 6 months, PFS rate with elacestrant was 38.18% vs. 23.47% with SOC in the overall population, and 43.79% vs. 23.83% in the ESR1 mutation population.

PFS rate at 12 months with elacestrant was 27.12% vs. 12.19% with SOC in the overall population, and 31.48% vs. 12.36% in the ESR1 mutation population.

In exploratory subgroup analyses, elacestrant significantly reduced the risk of progression or death and prolonged median PFS vs fulvestrant in all patients without prior chemotherapy (HR=0.636 [95% CI: 0.465-0.868]; median PFS 3.68 vs 1.97 months; P=0.0032), and in patients with mESR1 without prior chemotherapy (HR=0.487 (95% CI: 0.310-0.761; median PFS 5.32 vs 1.91 months; P=0.0015).

Elacestrant had a manageable safety profile in patients without prior chemotherapy consistent with the overall population.1

Dr. Virginia Kaklamani, breast medical oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center, commented, "Elacestrant is a potential exciting new endocrine therapy after progression on a CDK4/6 inhibitor in women with ER+ metastatic breast cancer. The EMERALD trial showed that elacestrant is active even in patients whose tumors harbor an ESR1 mutation. This subset analysis additionally showed that patients who have not previously been treated with chemotherapy in the metastatic setting had longer progression free survival up to 5.32 months."

Menarini plans to pursue combination studies and study the potential of elacestrant to be effective in addressing the highest unmet needs for ER+/HER2-patients.

Poster Presentation: 477

Abstract Title: Subgroup analysis of patients with no prior chemotherapy in EMERALD: A phase 3 trial evaluating elacestrant, an oral selective estrogen receptor degrader (SERD), vs investigator’s choice of endocrine monotherapy for ER+/HER2- advanced/metastatic breast cancer (mBC)

Abstract Number: 1100

Poster Session: Breast Cancer – Metastatic

About Elacestrant (RAD1901) and EMERALD Phase 3 Study

Elacestrant is an investigational selective estrogen receptor degrader (SERD), out-licensed to Menarini Group, which is being evaluated for potential use as a once daily oral treatment in patients with ER+/ HER2- advanced breast cancer. In 2018, elacestrant received fast track designation from the FDA. Preclinical studies completed prior to EMERALD indicate that the compound has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer. The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+/HER2- advanced/metastatic breast cancer patients. The study enrolled 477 patients who have received prior treatment with one or two lines of endocrine therapy, including a CDK 4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator’s choice of an approved hormonal agent. The primary endpoint of the study was progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations. Secondary endpoints included evaluation of overall survival (OS), objective response rate (ORR), and duration of response (DOR).

References

1. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022 May 18:JCO2200338. doi.org: 10.1200/JCO.22.00338. Epub ahead of print.

On June 6, 2022 SOPHiA GENETICS (Nasdaq: SOPH), the creator of a global data pooling and knowledge sharing platform that advances data-driven medicine, reported an update on its multimodal DEEP-Lung-IV clinical study (NCT04994795) at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Sophia Genetics, JUN 6, 2022, View Source [SID1234615668]). This will be discussed during the company’s joint Innovation Symposium with GE Healthcare Monday, June 6th from 6:30 – 8:00 pm CDT.

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Immunotherapy has revolutionized the management of metastatic non-small cell lung cancer. Despite its promise, the majority of patients fail to respond to the therapy while being exposed to potentially severe side effects. Existing biomarkers are suboptimal as they do not allow to predict which patients will benefit from the therapy. There is an urgent need to identify biomarkers that are predictive of response to immunotherapy at the individual patient level.

New agreement signed with GE Healthcare to utilize Imaging Fabric to further accelerate radiomics analysis workflows

SOPHiA GENETICS launched the DEEP-Lung-IV clinical study to leverage its multimodal machine learning-powered analytics capabilities to identify multimodal predictive signatures of response to immunotherapy for patients with advanced lung cancer. Through its global footprint, the study is intended to maximize exposure of the machine learning algorithms to a wide range of diverse, real-world data. Insights from the DEEP-Lung-IV study will power one of the applications of the CarePath module of the SOPHiA DDMTM platform, offering advanced data visualization, cohorting, and predictive capabilities in a single solution.

To date, 19 sites across seven countries have signed up for participation in the study, including Roswell Park Comprehensive Cancer Center in New York. "I am personally very excited to join the DEEP-Lung-IV study. I see tremendous value in the multimodal machine learning-powered approach to real-world data analytics and look forward to potentially applying it to other clinical questions of high relevance in lung cancer", said Dr. Prantesh Jain, Assistant Professor of Oncology at Roswell Park Comprehensive Cancer Center. Together, these sites have already recruited over 500 patients.

Early findings are promising and conceptually validate the potential for multimodal signatures to predict response to immuno-chemotherapy at the individual patient level. First results will be discussed during SOPHiA GENETICS’ joint Innovation Symposium with GE Healthcare on Monday, June 6, at 6:30 pm CDT.

"We are very excited by the strong operational traction in recruiting patients to the study, as well as the promising early findings. With its unique machine learning-powered multimodal study design and its focus on collecting very diverse real-world data from lung cancer patients around the world, we feel that the DEEP-Lung-IV study has the potential to usher a new era of precision medicine that would enable predictions at the individual patient level. We look forward to further validating our vision of building a multimodal decentralized collective intelligence, leveraging on real-world data to generate novel insights at the individual patient level," said Dr. Philippe Menu, SVP & Chief Medical Officer, SOPHiA GENETICS.

SOPHiA GENETICS has also entered into an agreement with GE Healthcare to utilize their Imaging Fabric Core and Imaging Fabric Annotation Template, as part of the Edison Digital Health Platform. In the context of the DEEP-Lung-IV clinical study, Imaging Fabric services will be used to visualize, segment, and annotate lung lesions for medical imaging visualization and annotation purposes. This allows SOPHiA GENETICS to further accelerate proprietary radiomics analytics workflows in the context of the study, in particular to move towards automatic whole-body tumor identification, segmentation, and quantification.

"We’re eager to further strengthen our collaboration with SOPHiA GENETICS. The use of Imaging Fabric and the SOPHiA DDMTM Platform are key to create the world of tomorrow, in which we aim to jointly break data silos across data modalities to deliver insights to physicians to help them optimize patient treatment workflows. We look forward to seeing how the DEEP-Lung-IV study results can help improve outcomes for those diagnosed with lung cancer," said Ben Newton, MD, General Manager, GE Healthcare Oncology Solutions.

SOPHiA GENETICS’ DEEP-Lung-IV clinical study aims to predict immunotherapy treatment response upon first evaluation at the individual patient level using data across multiple modalities including genomics, radiomics, clinical, and biological data. The study also aims to validate an algorithm that will allow the prediction of outcomes of the individual patient such as progression-free survival (PFS) and overall survival (OS). This predictive model will help identify patients that are likely to benefit from immunotherapy versus those that are not. It will stratify patients according to risk, helping clinicians make more informed therapeutic decisions for their patients, supporting biopharma to ensure the right patients are selected for clinical trials.

On June 6, 2022 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, reported that the Company will present at the 2022 Jefferies Global Healthcare Conference in New York, New York on Friday, June 10, 2022 at 10:30 a.m. ET. Presenting on behalf of Fusion will be Chief Executive Officer John Valliant, Ph.D (Press release, Fusion Pharmaceuticals, JUN 6, 2022, View Source [SID1234615667]).

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A live webcast of the event will be available on the "Events and Presentations" page in the "Investors & Media" section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 60 days following the presentation.