On December 9, 2020 Natera, Inc. (NASDAQ: NTRA), a pioneer and global leader in cell-free DNA testing, reported that new data will be presented on its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, in an oral presentation on December 10, 2020 at the 2020 European Society for Medical Oncology Immuno-Oncology (ESMO IO) Virtual Congress (Press release, Natera, DEC 9, 2020, View Source [SID1234572554]). The abstract is available to view here.

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The oral presentation will report results from a prospective circulating tumor DNA (ctDNA) analysis of 581 muscle invasive urothelial carcinoma (MIUC) patients who participated in IMvigor010, an open-label, global, randomized and controlled Phase III study that evaluated adjuvant treatment with the PD-L1 inhibitor atezolizumab compared with observation. Results at an interim analysis show that patients who were ctDNA-positive after surgery (37%) had an increase in overall survival (OS) in the treatment arm, with a median of 25.8 months with Tecentriq, compared with 15.8 months for observation (HR=0.59; 95% CI: 0.41–0.86), while those patients who were ctDNA-negative after surgery derived no benefit. The study also shows that ctDNA clearance was higher in the treatment arm vs. the observation arm (p=0.0048).

"In this study, we show that personalized ctDNA analysis is highly accurate not only for identifying molecular residual disease, but also for predicting better outcomes with immune therapy," said Thomas Powles, M.D., Professor, Barts Cancer Institute, and Principal Investigator of the study. "This opens new avenues for patient selection in the future and is an important step in the drive towards personalized cancer therapy."

"We are honored to partner with Genentech on this groundbreaking study," said Alexey Aleshin, M.D., Natera’s Senior Medical Director of Oncology. "This randomized Phase III study demonstrates for the first time, unequivocally, that Signatera can identify which patients are likely to benefit from adjuvant therapy and which are unlikely to benefit. It also highlights the significance of ctDNA clearance as an early endpoint for the evaluation of drug efficacy."

Details about the presentation are as follows:

Presentation #10 | Presenter: Thomas Powles, M.D. | Date and time: Dec 10, 13:50 – 14:02 CET

Clinical outcomes in post-operative ctDNA-positive muscle-invasive urothelial carcinoma (MIUC) patients after atezolizumab adjuvant therapy

About Signatera

Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for clinical and research use, and in 2019, it was granted Breakthrough Device Designation by the FDA. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. This maximizes accuracy for detecting the presence or absence of residual disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood. Unlike a standard liquid biopsy, Signatera is not intended to match patients with any particular therapy; rather, it is intended to detect and quantify how much cancer is left in the body, to detect recurrence earlier and to help optimize treatment decisions. Signatera test performance has been clinically validated in multiple cancer types including colorectal, non-small cell lung, breast, and bladder cancers. Signatera has been developed and its performance characteristics determined by Natera, the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified.

On December 9, 2020 PharmAbcine Inc. (KOSDAQ: 208340ks), a clinical-stage biotech company focusing on the development of fully human antibody therapeutics, reported the presentation of the latest interim data from its ongoing phase Ib combination trial of olinvacimab and pembrolizumab for metastatic triple-negative breast cancer (mTNBC) patients (Press release, PharmAbcine, DEC 9, 2020, View Source [SID1234572553]). The results were presented at the SABCS (San Antonio Breast Cancer Symposium) 2020, currently taking place virtually.

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As of the data cut-off date of September 2020, all 11 mTNBC patients were recruited and received at least one dose of treatment. No DLT (Dose Limiting Toxicity) was observed. Three patients were receiving treatment at the data cut-off date. 4 patients (36%) had partial response (PR) as best overall response, and 5 patients (45%) had clinical benefit (PR+SD≥24weeks). In the high-dose cohort, 3 patients (50%) showed PR and 4 patients (67%) received clinical benefit. 1 patient in PR showed complete response in the target lesion but was included in PR because a tumor was found in a non-target lesion.

The number of PR and SD remains the same from our previous interim results whose cut-off date was June 2020. The same 3 patients who were receiving treatment as of the previous cut-off date continued to receive treatment as of September 2020. As such, PFS (Progression Free Survival) and OS (Overall Survival) are likely to improve for the final results. Adverse events were similar to those shown in the previous interim results.

mTNBC is a highly malignant type of cancer that shows a high recurrence rate within the first five years after the diagnosis. mTNBC accounts for 10-20% of all breast cancers and shows a 5-year survival rate of approximately 11%. Unlike some other breast cancers, mTNBC does not express estrogen or progesterone receptors or human epidermal growth factor receptor 2 (HER2), and it does not respond to existing cancer drugs designed to target these markers. mTNBC is very difficult to treat, and there are very few FDA approved treatment options for these patients.

"The early activity signals for olinvacimab in combination with pembrolizumab for mTNBC patients are highly encouraging. We believe these findings provide an encouraging safety profile and evidence of clinical activity of the combo therapy," said Dr. Jin-San Yoo, CEO of PharmAbcine. "We are particularly thrilled by the efficacy data from the high-dose cohort, heightening our expectation for its continued clinical development or future planned clinical studies."

About San Antonio Breast Cancer Symposium

San Antonio Breast Cancer Symposium (SABCS) is the world’s largest breast cancer conference held annually. Nearly 10,000 researchers and medical experts participate event every year. The core mission of this event is to provide the latest research data in breast oncology to all participants around the globe. For the safety and security of all members in the COVID-19 global pandemic, the SABCS executive committee has decided to hold this year’s event virtually.

On December 9, 2020 TVAX Biomedical (TVAX), is a cancer immunotherapy company reported that is moving into its pivotal glioblastoma study for FDA regulatory approval (Press release, TVAX Biomedical, DEC 9, 2020, View Source [SID1234572552]). TVAX Immunotherapy could fundamentally change the way cancer is treated as T cells can kill all cancer cells, including cancer stem cells, without the toxicity of current treatments. With early promising outcomes, TVAX received Fast Track Designation and Orphan Product Designation from the FDA.

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Glioblastoma is an incurable brain cancer affecting >12,000 people annually in the US. This form of brain cancer killed Beau Biden, the son of President-elect Biden, and Senators John McCain and Ted Kennedy and countless others. TVAX is working to change that.

TVAX Immunotherapy is a cutting-edge approach to cellular therapy. The individualized therapy first helps the patient develop immunity against their cancer and the unique "neoantigens" that cancer cells produce. Next, T cells are removed from patient’s blood and activated in TVAX’s specialized manufacturing facility. Patients are then treated with billions of their own "killer" T cells that attack their cancer. Dr. Wayne Carter, TVAX Biomedical’s CEO, explains it like this, "TVAX’s technology uses ‘killer’ T cells that function like billions of smart bombs hunting and destroying cancer cells throughout the body. TVAX Immunotherapy has very few side effects because ‘killer’ T cells kill cancer cells, not normal cells."

This therapy has shown promising results for four-legged friends too. The ability to treat multiple types of cancer prompted TVAX to spin-off its animal health division into Elias Animal Health, an affiliate pursuing similar treatments in dogs. Elias is using the technology to treat osteosarcoma, an incurable bone cancer and is currently enrolling dogs for their registration study with the USDA.

TVAX Immunotherapy has been administered to more than 120 patients and has demonstrated efficacy against several cancers, producing numerous long-lasting complete and partial responses with none of the "off-target" short and long-term toxicity seen with CAR-T cell therapy, checkpoint inhibitors, and chemotherapies.

TVAX worked closely with the FDA to plan its critical glioblastoma registration study. Fast Track Designation affords many advantages, including a pathway to accelerated marketing approval. TVAX Immunotherapy has dramatically lower manufacturing costs compared to other cellular immunotherapies such as CAR-T therapies and manufacturing can be easily automated to facilitate large-scale commercialization.

On December 9, 2020 Kazia Therapeutics Limited (ASX: KZA;NASDAQ: KZIA), an Australian oncology-focused biotechnology company, reported to share top-line final data from its phase I study of Cantrixil (TRX-E-002-1) in patients with persistent or recurrent ovarian cancer (NCT02903771) (Press release, Kazia Therapeutics, DEC 9, 2020, View Source [SID1234572551]).

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Key Points

25 patients with advanced metastatic ovarian cancer received at least one dose of Cantrixil at six sites in the United States and Australia, comprising 11 patients in Part A (dose escalation) and 14 patients in Part B (dose expansion)
Trial achieved its primary objective, determining the maximum tolerated dose (MTD) of Cantrixil to be 5 mg/kg
Overall, 16 patients were evaluable for efficacy. One patient demonstrated a complete response (CR) and two patients experienced a partial response (PR), according to industry-standard RECIST criteria, making an overall response rate (ORR) of 19%
The patient who experienced a complete response remains in remission some three years after her last dose of Cantrixil
The drug was generally well-tolerated, with primarily gastrointestinal toxicities observed (abdominal pain, vomiting, and nausea)
Australian lead investigator, Associate Professor Jim Coward, commented, "this was a heavily pre-treated population, comprising patients with very advanced disease. Existing treatment options for such patients are limited, and there remains an urgent need for new therapies. My colleagues and I are excited by the potential for Cantrixil to provide benefit here, and we look forward to seeing the drug move forward in its development."

Kazia expects the full data to be presented at a suitable academic conference and published in a peer-reviewed journal in 1H CY2021. In accordance with common practice, the full data will remain embargoed until they are formally published, in order not to prejudice the appropriate dissemination of the data, and only top-line data are discussed here.

Kazia CEO, Dr James Garner, commented, "we are very pleased to see the Cantrixil phase I study completed. The data unambiguously demonstrates the potential for Cantrixil to provide benefit in this very challenging patient population. With this positive data in hand, our focus now shifts to partnering activity, and we hope to transition Cantrixil to a company which both shares our belief in its potential and is able to apply the necessary resources and expertise to realise that potential over the next chapter of its development."

Background

The phase I study of Cantrixil in ovarian cancer (NCT02903771) commenced recruitment in December 2016. It was designed in two parts. Part A (dose escalation component) was intended to determine the maximum tolerated dose (MTD) of Cantrixil in women with ovarian cancer. Part B (dose expansion cohort) was intended to seek preliminary evidence of clinical efficacy, as well as providing a deeper understanding of pharmacokinetics and safety of Cantrixil. All patients received two cycles of treatment with Cantrixil monotherapy, followed by up to six cycles in combination with other chemotherapy agents.

Kazia announced completion of Part A in October 2018. At that stage, the study declared 5 mg/kg to be the MTD, and this dose was used for all patients in Part B. The main dose-limiting toxicity (DLT) was abdominal pain. 11 patients received at least one dose of Cantrixil in Part A.

Part B recruited an additional 14 patients, all of whom were treated at the MTD, with the goal of seeking exploratory signals of potential clinical efficacy. All 14 patients received at least one dose of Cantrixil in Part B. In total, 17 patients across Part A and Part B received Cantrixil at the MTD of 5 mg/kg.

The study completed recruitment in August 2019, and last patient last visit occurred in March 2020. Preliminary efficacy data was presented in September 2019 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting in Barcelona, Spain, and at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Meeting in June 2020.

On December 9, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported updates on the clinical development of the company’s novel Bcl-2 inhibitor APG-2575, further demonstrating the drug candidate’s therapeutic potential (Press release, Ascentage Pharma, DEC 9, 2020, View Source [SID1234572550]).

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APG-2575 is a novel, orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. APG-2575 is designed to treat hematologic malignancies and solid tumors by selectively blocking antiapoptotic protein Bcl-2 to restore the normal apoptosis process in cancer cells. As a bona fide Bcl-2 inhibitor, APG-2575 demonstrated desired target engagement. APG-2575 selectively binds to Bcl-2, disrupts Bcl-2:BIM complexes, and releases the proapoptotic protein BIM. Freed BIM subsequently activates BAX/BAK for pore formation on the mitochondria membrane, leading to mitochondrial outer-membrane permeabilization (MOMP), cytochrome c release, caspase activation, and apoptosis of cancer cells. APG-2575 is the first China-developed Bcl-2 inhibitor having entered clinical development in China. As a single agent, APG-2575 has potent antitumor activity in Bcl-2-dependent tumor cells, and has shown a broad range of antitumor activities when combined with other oncologic drugs. Previously, APG-2575 had received clearances and approvals for multiple Phase Ib/II clinical studies in China, Australia, and the US, and is currently being developed in a range of hematologic malignancies globally.

Highlights of the update

In total, 9 clinical studies are ongoing globally, with over 100 patients who have been administered APG-2575 at doses ranging from 20 mg to 1200 mg for the treatment of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), acute myeloid leukemia (AML), and high leukocyte acute leukemia (HCL), etc.
Studies of APG-2575 in the treatment of relapsed/refractory CLL (r/r CLL) have enrolled over 30 patients. Preliminary results show that an objective response rate (ORR) of 70% has been reached in evaluable patients.
On safety:
Maximum tolerated dose (MTD) has not been reached, and no dose-limiting toxicity (DLT) was observed.
No clinical or laboratory tumor lysis syndrome (TLS) was observed.
Most treatment-related adverse events (TRAEs) were of Grade 1 or 2.
Limited cases of neutropenia and thrombocytopenia.
APG-2575 has been granted three Orphan Drug Designations (ODDs) by the US FDA, for the treatment of CLL, MM, and Waldenström macroglobulinemia (WM).
"APG-2575 is a key drug candidate of Ascentage Pharma’s apoptosis-targeted pipeline," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "As the first China-developed Bcl-2 inhibitor having entered clinical development in China, APG-2575 as a single agent or in combinations has demonstrated great therapeutic potential and clinical advantages. We are accelerating the global clinical development of this drug candidate, which we hope will soon translate into a new therapeutic option for patients in China and around the world."