On October 28, 2020 AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)’s Enhertu (trastuzumab deruxtecan) reported that it has received acceptance for its supplemental Biologics License Application (sBLA) and has also been granted Priority Review in the US for the treatment of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (Press release, AstraZeneca, OCT 28, 2020, View Source [SID1234569181]).

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The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that offer significant advances over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance. The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, will be during the first quarter of 2021.

There are more than 27,000 new cases of gastric cancer in the US each year, of which approximately one in five are HER2 positive.1,2 For patients with metastatic gastric cancer who progress on initial treatment with an anti-HER2 medicine, there are no other approved HER2-directed medicines.

José Baselga, Executive Vice President, Oncology R&D, said: "Once patients with HER2-positive metastatic gastric cancer progress following initial treatment with an anti-HER2 regimen, there are no approved HER2-directed medicines. The prognosis for these patients is poor, as available treatment options offer only limited clinical benefit. This milestone brings us one step closer to delivering a potentially practice-changing medicine to patients with gastric cancer in the US."

Antoine Yver, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo, said: "The results of the DESTINY-Gastric01 trial are unprecedented as they represent the first time a HER2-directed medicine has demonstrated an improvement in survival following chemotherapy and HER2 treatment in the metastatic setting. Building on the recent Breakthrough Therapy Designation, the filing of the application and Priority Review by the FDA for this potential new indication for Enhertu reflects the importance of the data and the significant unmet need for patients with previously treated HER2-positive metastatic gastric cancer."

The sBLA was based on results from the DESTINY-Gastric01 randomised Phase II trial, which demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR), the primary endpoint, and overall survival (OS), a key secondary endpoint, for patients treated with Enhertu versus chemotherapy (paclitaxel or irinotecan monotherapy).

The safety and tolerability profiles of Enhertu in DESTINY-Gastric01 were consistent with that observed in the gastric cancer cohort of the Phase I trial and previously reported Enhertu trials in other tumours.3 The most common Grade 3 or higher treatment-emergent adverse events were decreased neutrophil count, anaemia, decreased white blood cell count and decreased appetite. There were 12 (9.6%) cases of confirmed treatment-related interstitial lung disease (ILD) or pneumonitis in 125 patients treated with Enhertu as determined by an independent review committee. The majority of cases were Grade 1 or 2 with two Grade 3, one Grade 4 and no Grade 5 (ILD-related deaths).

The results from the trial were presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program and simultaneously published online in The New England Journal of Medicine in May 2020.4

Enhertu received Breakthrough Therapy Designation from the FDA in May 2020 for patients with unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma who have received two or more prior regimens including trastuzumab and Orphan Drug Designation for patients with gastric cancer, including GEJ adenocarcinoma. Enhertu has not been approved in the US for gastric or GEJ adenocarcinoma.

Gastric cancer

Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality with a five-year survival rate of 5% for metastatic disease; there were approximately one million new cases reported in 2018 and 783,000 deaths.5,6 In the US, it is estimated that 27,600 new cases of gastric cancer will be diagnosed in 2020 and more than 11,000 people will die from the disease.1

Approximately one in five gastric cancers are HER2 positive.2 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers. Gastric cancer is usually diagnosed in the advanced stage, but even when diagnosed in earlier stages of the disease, the survival rate remains modest.7 Recommended 1st-line treatment for HER2-positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy. For metastatic gastric cancer that progresses on 1st-line treatment, there are no other approved HER2-targeted medicines.8

DESTINY-Gastric01

DESTINY-Gastric01 is a Phase II, open-label, multi-centre, randomised controlled trial testing the safety and efficacy of Enhertu versus investigator’s choice of chemotherapy in a primary cohort of 188 patients from Japan and South Korea with HER2-positive (defined as IHC3+ or IHC2+/ISH+), advanced gastric or GEJ adenocarcinoma who have progressed on two or more prior treatment regimens including fluoropyrimidine and platinum chemotherapy and trastuzumab. Patients were randomised 2:1 to receive Enhertu or investigator’s choice of chemotherapy (paclitaxel or irinotecan monotherapy). Patients were treated with Enhertu 6.4mg/kg once every three weeks or chemotherapy.

The primary endpoint of the trial is ORR, as assessed by independent central review. OS, a key secondary endpoint, was to be evaluated hierarchically at a prespecified interim analysis if the primary endpoint was statistically significant. Additional efficacy endpoints include progression-free survival, duration of response, disease control rate and confirmed ORR assessed in those responses confirmed by a follow-up scan of at least four weeks after initial independent central review.9

Enhertu

Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the US) is a HER2-directed antibody drug conjugate (ADC) and is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (‘payload’) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Enhertu is comprised of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload by a tetrapeptide-based linker.

Enhertu (5.4mg/kg) is approved in the US and Japan for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 trial, and is under accelerated assessment in the EU for HER2-positive metastatic breast cancer. In September 2020, Enhertu (6.4mg/kg) was approved in Japan for patients with HER2-positive unresectable advanced or recurrent gastric cancer that progressed after chemotherapy.

Enhertu clinical development

Enhertu clinical development table
aTrials led by AstraZeneca bNew trials that have been added to the clinical development programme and have achieved FPCD cEnhertu arm added to ongoing AstraZeneca trial.

Collaboration between AstraZeneca and Daiichi Sankyo

AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and DS-1062 (a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and DS-1062.

AstraZeneca in gastrointestinal cancers

AstraZeneca has a broad development programme for the treatment of gastrointestinal (GI) cancers across several medicines spanning a variety of tumour types and stages of disease. In 2018, GI cancers collectively represented nearly five million new cancer cases leading to more than 3.5 million deaths.5 Within this programme, the Company is committed to improving outcomes in gastric, liver, oesophageal, pancreatic, and colorectal cancers.

The Company aims to understand the potential of Enhertu in the two most common GI cancers, colorectal and gastric cancers.5 Lynparza (olaparib) is a first-in-class PARP inhibitor with a broad and advanced clinical trial programme across multiple GI tumour types including pancreatic and colorectal cancers. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada). Imfinzi (durvalumab) is being assessed both as monotherapy and in combinations including with tremelimumab across the two main types of liver cancer, hepatocellular carcinoma and biliary tract cancer, and in oesophageal and gastric cancers.10

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

On October 27, 2020 Aptose Biosciences Inc. (Nasdaq: APTO; TSX: APS), a clinical-stage company developing highly differentiated therapeutics that target the underlying mechanisms of cancer, reported that it will release its financial results for the quarter ended September 30, 2020 on Tuesday, November 10, 2020, after the close of the market (Press release, Aptose Biosciences, OCT 27, 2020, View Source [SID1234573619]).

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Conference Call & Webcast:

Date: Tuesday, November 10, 2020
Time: 5:00 PM ET
Dial In – Toll-Free: 1 844-882-7834
Dial In – International: 1 574-990-9707
Passcode: 5539639
Webcast: LINK
Replay available through November 24, 2020:

Dial In – Toll-Free: 1 855-859-2056
Dial In – International: 1 404-537-3406
Replay Passcode: 5539639
The live conference call can also be accessed through a link on the Investor Relations section of Aptose’s website at View Source An archived version of the webcast along with a transcript will be available on the company’s website for 30 days.

The press release, the financial statements and the management’s discussion and analysis for the quarter ended September 30, 2020, will be available on SEDAR at www.sedar.com and EDGAR at www.sec.gov/edgar.shtml.

On October 27, 2020 Redx Pharma plc (AIM: REDX), the drug discovery and development company focused on cancer and fibrosis, reported that it has appointed Dr Jane Robertson as Chief Medical Officer (Press release, Redx Pharma, OCT 27, 2020, View Source [SID1234573528]). Jane is a well respected UK haemato-oncologist with over 17 years’ experience of clinical development in oncology and has a breadth of experience investigating multiple tumours and agents including VEGF inhibitors, anti-hormonals, PARP inhibitors, nucleotide analogs and most recently cell therapies. She will commence her role at Redx on 1 March 2021.

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Jane joins Redx from her position as Chief Medical Officer at Achilles Therapeutics Ltd, a biotech company focused on the creation of a personalized T cell therapy directed against clonal tumour neoantigens. During her tenure at Achilles, the Company progressed its lead candidate into two clinical trials. Prior to Achilles, Jane served as the Chief Medical Officer at Nucana Biomed Ltd and at Kesios Therapeutics Ltd. She has previously also held a number of senior R&D leadership roles at AstraZeneca Oncology, notably leading the development of the first in class PARP inhibitor, olaparib. Jane originally trained in general medicine and haematology, working in clinical practice and translational research settings, and sub-specialising in haemato-oncology; she remains General Medical Council registered.

Lisa Anson, Chief Executive Officer of Redx Pharma commented: "We are absolutely delighted that Jane has chosen to join our team at this exciting stage in Redx’s development. As our Chief Medical Officer, her extensive and varied experience in big pharma, biotech and clinical practice, will be invaluable as we further progress our pipeline into clinical development."

Jane Robertson, incoming Chief Medical Officer, Redx Pharma commented: "I have been very impressed by Redx and its outstanding scientific team, and am really looking forward to the opportunity to progress the Company’s promising pipeline into differentiated clinical stage programmes in the treatment of fibrotic diseases and cancer. With data expected from Redx’s Phase 1 RXC004 study in H1 2021, this feels like a particularly exciting time to be joining the Company." Following a handover, Dr Andrew Saunders will leave Redx after 3 years as Chief Medical Officer to pursue other opportunities. Lisa Anson added, "On behalf of all of Redx and the Board, I would like to thank Andrew for his great work in overseeing the transition of RXC004 into phase 1 and his strategic guidance in our planned future development plans for RXC004."

On October 27, 2020 Genome & Company (KONEX: 314130), a global pioneer company of microbiome therapeutics, reported that it initiated clinical trial of GEN-001, an anti-cancer microbiome therapeutic (NCT04601402) (Press release, Genome & Company, OCT 27, 2020, View Source [SID1234571039]).

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GEN-001 is an oral microbiome therapeutic candidate of Genome & Company, and in this clinical trial, it will be administered to patients with cancer in combination with an immune checkpoint inhibitor, which is the first among Asian microbiome development companies.

The phase 1 study aims to determine the RP2D (recommended Phase 2 dose) of GEN-001 in combination with BAVENCIO (avelumab). Avelumab is an anti-PD-L1 checkpoint inhibitor co-developed and co-commercialized by Merck KGaA, Darmstadt, Germany and Pfizer Inc. In the phase 1b study, the safety and preliminary efficacy of the combination therapy at the RP2D of GEN-001 in combination with BAVENCIO for patients with specific solid tumors will be investigated.

A total of three clinical sites including OHSU Knight Cancer Institute located in Portland, Oregon will complete the dose-escalation cohort within the first half of 2021. The OHSU Knight Cancer Institute is one of the globally renowned cancer centers and is one of the 51 National Cancer Institute (NCI) designated Comprehensive Cancer Center in the U.S. Amid harsh conditions due to COVID-19 since the beginning of 2020, close collaboration among OHSU, contract research organization and Genome & Company enabled this clinical trial to be initiated just six months after its IND to FDA went into effect.

"We are pleased to offer our patients access to a new clinical trial of the drug GEN-001 in combination with avelumab," said Shivaani Kummar, M.D., head of the division of hematology and medical oncology in the OHSU School of Medicine, and co-director of the OHSU Knight Cancer Institute Center for Experimental Therapeutics. "Our goal is to learn more about whether this combination therapy will be effective in overcoming acquired resistance to anti-PD-(L)1 therapy in patients with advanced solid tumors whose disease has progressed on prior anti-PD-(L)1 therapy."

Dr. Jisoo Pae, CEO of Genome & Company also stated, "The study outcome of GEN001-101 will investigate the preliminary efficacy of GEN-001 in patients with various cancers. We hope to see clinically meaningful results fairly soon which in turn would allow us to continue making progress GEN-001 clinical trials, with the potential to eventually become an alternative therapeutic option in the immuno-oncology market."

In December 2019, Genome & Company entered into the Clinical Trial Collaboration and Supply Agreement with Merck KGaA and Pfizer Inc. (this "Agreement") to evaluate the safety, tolerability, and biological and clinical activities of GEN-001 therapy in combination with avelumab, a human anti-PD-L1 therapy, in multiple cancer indications. Under the terms of this Agreement, Genome & Company will be the sponsor of the study, and Merck and Pfizer will supply avelumab for the phase 1/1b clinical trial.

BAVENCIO is a trademark of Merck KGaA, Darmstadt, Germany.

▶Avelumab Approved Indications

Avelumab (BAVENCIO) is indicated in the US for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy. BAVENCIO is also indicated for the treatment of patients with locally advanced or metastatic UC who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Avelumab in combination with axitinib is approved in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab Important Safety Information from the US FDA-Approved Label

The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis and hepatitis [including fatal cases], colitis, endocrinopathies, nephritis, and other immune-mediated adverse reactions as a single agent or in combination with axitinib [which can be severe and have included fatal cases]), infusion-related reactions, hepatotoxicity in combination with axitinib, major adverse cardiovascular events (MACE) in combination with axitinib [which can be severe and have included fatal cases], and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO monotherapy include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction peripheral edema, decreased appetite, urinary tract infection and rash. Common adverse reactions (reported in at least 20% of patients) in patients receiving BAVENCIO in combination with axitinib include diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Grade 3-4 hematology laboratory value abnormalities reported in at least 10% of patients with Merkel cell carcinoma treated with BAVENCIO monotherapy include lymphopenia; in patients receiving BAVENCIO in combination with axitinib, grade 3-4 clinical chemistry abnormalities include blood triglyceride increased and lipase increased.

On October 7, 2020 Cannabics Pharmaceuticals Inc. (OTCQB: CNBX), a global leader in the development of cancer related cannabinoid-based therapeutic formulations and medicines, reported that it has been informed by the European Patent Office that the examining division intends to grant the company a European Patent for the Company’s application titled "A System and Method for High Throughput Screening of Cancer Cells (Press release, Cannabics Pharmaceuticals, OCT 27, 2020, View Source [SID1234570699])."

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Drug Sensitivity Heatmap of Multiple Cannabinoids and Cancer Cells

This patent application relates to the company’s CANNABICS CDx companion diagnostic drug sensitivity test, whereby a patient’s biopsy is screened to match the optimal cannabinoid combination available using the company’s high throughput screening of cancer cells proprietary technology.

Outside the European territory, this patent is also currently being reviewed in other territories including the US and Canada. The decision of the European examiner is significant in that it could also accelerate the review process in other territories who offer a Patent Prosecution Highway such as Canada, India, Mexico and Brazil.

Gabriel Yariv, Cannabics Pharmaceuticals’ President and COO said: "This patent exemplifies our pioneering vision to bring Cannabinoid-based therapies and treatments to cancer patients worldwide and will strengthen our position as we concentrate on penetrating the European market".

Dr. Eyal Ballan, Cannabics Pharmaceuticals’ CTO, said:" As pioneers in Cannabinoid-based Cancer diagnostics, we have always believed in the novelty and uniqueness of our vision to personalize cannabinoid treatments. The intention of the European examiner to grant our patent is certainly a positive vindication for our efforts".