On December 14, 2020 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca reported the initiation of TROPION-Lung05, a global phase 2 trial of datopotamab deruxtecan (Dato-DXd; DS-1062), a TROP2 directed antibody drug conjugate (ADC), in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with actionable genomic alterations previously treated with kinase inhibitor therapy and platinum-based chemotherapy with or without immunotherapy (Press release, Daiichi Sankyo, DEC 14, 2020, View Source [SID1234572821]).

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Targeted therapy with tyrosine kinase inhibitors (TKIs) is recommended as first-line or in subsequent lines of treatment in patients with advanced or metastatic NSCLC that tests positive for certain genomic alterations as TKIs offer improved response rates or survival compared to traditional chemotherapy.1 However, once a patient develops acquired resistance to TKIs, treatment options become more limited.1,2

TROP2 expression has been associated with poor overall and disease-free survival in several types of solid tumors. TROP2 expression has been observed in the majority of adenocarcinoma and squamous cell carcinoma NSCLC.3,4,5 There are no TROP2 directed therapies or ADCs currently approved for the treatment of NSCLC.

"Following preliminary findings of durable responses observed in TROPION-PanTumor01, the ongoing phase 1 trial of datopotamab deruxtecan in non-small cell lung cancer, we will evaluate whether targeting TROP2 with our DXd ADC technology could be a new treatment strategy for patients with previously treated advanced or metastatic non-small cell lung cancer with actionable genomic alterations," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo.

"Many patients with NSCLC will ultimately develop resistance to available targeted therapies, and treatment options for advanced NSCLC are limited," said Cristian Massacesi, Senior Vice President, Head of Late Stage Development Oncology R&D, AstraZeneca. "TROPION-Lung05 provides an opportunity to evaluate datopotamab deruxtecan, a targeted ADC approach with promise in this patient population."

About TROPION-Lung05

The global, multicenter, single-arm, open-label phase 2 study will evaluate the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) in patients with advanced or metastatic NSCLC with actionable genomic alterations with progression on or after at least one tyrosine kinase inhibitor and at least one regimen of platinum-based chemotherapy (with or without other systemic therapies). Patients with one or more genomic alterations including EGFR, ALK, ROS1, NTRK, BRAF, RET, or MET exon 14 skipping who received up to four prior lines of treatment are eligible for the study.

The primary trial endpoint is overall response rate as assessed by blinded independent central review. Secondary efficacy endpoints include duration of response, best percentage change in the sum of diameters of measurable tumors, disease control rate, clinical benefit rate, progression-free survival, time to response, objective response rate and overall survival. Safety endpoints include treatment emergent adverse events and other safety parameters. Pharmacokinetic and immunogenicity endpoints also will be evaluated.

The study will enroll patients at multiple sites in North America, Europe and Asia. For more information visit Clinicaltrials.gov.

About Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide; there were an estimated 2.1 million new cases of lung cancer in 2018 and 1.8 million deaths.6 NSCLC accounts for 80 to 85 percent of all lung cancers.7

The majority of patients with advanced NSCLC traditionally received platinum-based chemotherapy as first-line treatment.8 The introduction of targeted therapies and immune checkpoint inhibitors in the past two decades has created new options and shifted treatment to a more personalized approach.8

A number of targeted tyrosine kinase inhibitors, which offer improved survival rates over traditional chemotherapy regimens, are approved for treatment of NSCLC with specific genomic alterations.1 The most common alterations for which kinase inhibitors are approved are EGFR (approximately 10 to 35% frequency) and ALK rearrangement (approximately 3 to 7%). All patients eventually develop resistance to available therapies.2

About TROP2

TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is overexpressed in many cancers.9 TROP2 expression has been associated with poor overall and disease-free survival in several types of solid tumors. TROP2 expression has been observed in up to 64% of adenocarcinoma and up to 75% of squamous cell carcinoma NSCLC.3,4,5 There are no TROP2 directed therapies or ADCs currently approved for the treatment of NSCLC.

About Datopotamab Deruxtecan (Dato-DXd; DS-1062)

Datopotamab deruxtecan (Dato-DXd; DS-1062) is one of three lead DXd antibody drug conjugates (ADCs) in the oncology pipeline of Daiichi Sankyo.

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. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG13 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable linker with a drug-to-antibody ratio (DAR) of four.

TROPION is the broad and comprehensive clinical development program to evaluate the efficacy and safety of datopotamab deruxtecan across multiple TROP2 cancers as both a monotherapy and in combination with other anticancer treatments. In addition to TROPION-Lung05, datopotamab deruxtecan is currently being evaluated in a number of clinical trials, including TROPION-Lung01, a phase 3 study in patients with advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations and TROPION-PanTumor01, a phase 1 study in patients with advanced solid tumors that have progressed on standard treatments or for whom no standard treatment is available, which has completed enrollment of patients into a unresectable advanced NSCLC cohort and is currently enrolling patients into a triple negative breast cancer (TNBC) cohort.

Datopotamab deruxtecan is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About the Collaboration between Daiichi Sankyo and AstraZeneca

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize trastuzumab deruxtecan (a HER2 directed ADC) in March 2019, and datopotamab deruxtecan (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 trastuzumab deruxtecan and datopotamab deruxtecan.

About Daiichi Sankyo Cancer Enterprise

The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by our DXd antibody drug conjugate (ADC) technology, our powerful research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. For more information, please visit: www.DSCancerEnterprise.com.

On December 14, 2020 Legend Biotech Corporation (NASDAQ: LEGN) ("Legend Biotech"), a global clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and other indications, reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application to evaluate LB1901, the company’s investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy, for the treatment of adults with relapsed or refractory T-cell lymphoma (TCL) (Press release, Legend Biotech, DEC 14, 2020, View Source [SID1234572820]). Under this IND, Legend will initiate a Phase 1 clinical study for LB1901 in the United States.

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LB1901 is an investigational CAR-T product targeting CD4, which is a surface membrane glycoprotein uniformly expressed in a majority of TCL subtypes. A Phase 1, first-in-human, open-label, multicenter, multicohort clinical study will enroll patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) in the United States. The primary objectives of the study are to characterize the safety and tolerability of LB1901 and to determine the recommended Phase 2 dose.

TCL is a heterogeneous group of disorders accounting for less than 15 percent of Non-Hodgkin lymphoma cases in the US.1,2 PTCL comprises subtypes which are uncommon and often aggressive, with a 5-year overall survival of 39% that varies by subtype.3,4 Cutaneous T-cell lymphomas are a group of T-cell malignancies, which occur primarily in the skin.5 Despite current treatment options, a substantial proportion of patients with PTCL or CTCL experiences relapse. A high unmet medical need remains for patients with relapsed or refractory PTCL and CTCL.

"The FDA’s clearance of Legend’s IND application for LB1901 is a milestone representative of the company’s scientific expertise in cell therapy innovation," said Ying Huang, PhD, Chief Executive Officer and Chief Financial Officer of Legend Biotech. "We look forward to working with the investigators as we explore its potential in meeting the great unmet medical needs in the TCL population."

On December 14, 2020 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to cures for blood cancers and serious hematologic diseases, reported that the company conducted a Type B Meeting for omidubicel with the U.S. Food and Drug Administration (FDA) on Friday, December 11, 2020 (Press release, Gamida Cell, DEC 14, 2020, View Source [SID1234572819]).

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During the meeting, the FDA provided encouraging feedback regarding the Phase 3 study of omidubicel pertaining to the pre-specified primary and secondary endpoints. The FDA also recommended that Gamida Cell generate additional manufacturing-related data prior to requesting a pre-Biologics License Application (BLA) meeting. Specifically, the FDA requested that Gamida Cell demonstrate analytical and clinical comparability from the company’s planned commercial manufacturing sites. The company believes the clinical comparability requirement will be met if the time to neutrophil engraftment in patients from the company’s ongoing expanded access program (EAP) using omidubicel produced at Gamida Cell’s planned commercial manufacturing sites is consistent with the results achieved in the Phase 3 clinical trial. Based on the feedback received at the meeting with FDA, Gamida Cell intends to submit a full BLA for omidubicel in the second half of 2021 in lieu of the company’s previous plan to initiate a rolling BLA submission by the end of 2020. The revised plan could support a potential commercial launch of omidubicel in the United States as early as mid-2022.

"Although we are disappointed by the delay in timing to bring omidubicel to patients after a potential FDA approval, we are encouraged by the FDA’s reaction to our Phase 3 data as the pivotal trial of omidubicel achieved pre-specified primary and secondary endpoints. Commercial manufacturing readiness activities are underway, and we believe we will be able to complete all the requirements discussed with FDA," said Julian Adams, Ph.D., chief executive officer of Gamida Cell. "With this clarity, we look forward to proceeding towards a full BLA submission in the second half of 2021. We continue to prepare for the commercialization of omidubicel on the revised timeline, as we continue to provide omidubicel to patients in need through our expanded access program."

The planned BLA submission for omidubicel is supported by a Phase 3 study which met its primary and secondary endpoints. The international, multi-center, randomized Phase 3 study was designed to evaluate the safety and efficacy of omidubicel in patients with hematologic malignancies undergoing a bone marrow transplant compared to a comparator group of patients who received a standard umbilical cord blood transplant. Omidubicel is the first bone marrow transplant cell therapy product to receive Breakthrough Therapy Designation from the FDA and has also received Orphan Drug Designation in the U.S. and EU.

As previously announced, given the encouraging Phase 1 data presented at the 2020 ASH (Free ASH Whitepaper) meeting, the company also plans to submit an IND for GDA-201, its expanded natural killer cell investigational therapy, in 2021.

About Omidubicel

Omidubicel is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant solution for patients with hematologic malignancies (blood cancers). In both Phase 1/2 and Phase 3 clinical studies (NCT01816230, NCT02730299), omidubicel demonstrated rapid and durable time to engraftment and was generally well tolerated. Omidubicel is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937). The aplastic anemia investigational new drug application is currently filed with the FDA under the brand name CordIn, which is the same investigational development candidate as omidubicel. For more information on clinical trials of omidubicel, please visit www.clinicaltrials.gov.

Omidubicel is an investigational therapy, and its safety and efficacy have not been established by the U.S. Food and Drug Administration or any other health authority.

About GDA-201

Gamida Cell applied the capabilities of its NAM-based cell expansion technology to develop GDA-201, an innate natural killer (NK) cell immunotherapy for the treatment of hematologic and solid tumors in combination with standard of care antibody therapies. GDA-201 addresses key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs of NK cells expanded in culture. GDA-201 is in Phase 1 development through an investigator-sponsored study in patients with refractory non-Hodgkin lymphoma and multiple myeloma.1 For more information on the clinical study of GDA-201, please visit www.clinicaltrials.gov.

GDA-201 is an investigational therapy, and its safety and efficacy has not been established by the U.S. Food and Drug Administration or any other health authority.

On December 14, 2020 Novocure (NASDAQ:NVCR) reported that the Swiss Federal Office of Public Health (BAG) has added Optune in combination with temozolomide to the List of Remedies and Equipment (MiGeL) for the treatment of patients with newly diagnosed glioblastoma (GBM), effective April 1, 2021 (Press release, NovoCure, DEC 14, 2020, View Source [SID1234572818]). The List of Remedies and Equipment defines which medical devices are covered by compulsory health insurance in Switzerland.

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"We are extremely pleased that Switzerland has established national reimbursement for Optune," said Thomas Hefti, Vice President Europe and Emerging Markets (EMEA). "Access to our therapy continues to grow throughout the world, demonstrating health insurers’ increasing recognition of Optune."

"National reimbursement of Optune for newly diagnosed GBM patients in Switzerland represents an incredible effort by our team to expand access to our therapy as well as an increased understanding of the benefits of our therapy among health insurers," said Pritesh Shah, Novocure’s Chief Commercial Officer. "We are proud of this accomplishment and will continue working diligently to expand access to GBM patients who may benefit."

About Optune
Optune is a noninvasive, antimitotic cancer treatment for GBM. Optune delivers Tumor Treating Fields to the region of the tumor.

Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division. Tumor Treating Fields does not stimulate or heat tissue and targets dividing cancer cells with specific membrane properties. Tumor Treating Fields causes minimal damage to healthy cells. Mild to moderate skin irritation is the most common side effect reported. Tumor Treating Fields is approved in certain countries for the treatment of adults with GBM and in the U.S. for MPM, two of the most difficult cancer types to treat. The therapy shows promise in multiple solid tumor types – including some of the most aggressive forms of cancer.

Approved Indications
Optune is intended as a treatment for adult patients (22 years of age or older) with histologically-confirmed glioblastoma multiforme (GBM).

Optune with temozolomide is indicated for the treatment of adult patients with newly diagnosed, supratentorial glioblastoma following maximal debulking surgery, and completion of radiation therapy together with concomitant standard of care chemotherapy.

For the treatment of recurrent GBM, Optune is indicated following histologically- or radiologically-confirmed recurrence in the supratentorial region of the brain after receiving chemotherapy. The device is intended to be used as a monotherapy, and is intended as an alternative to standard medical therapy for GBM after surgical and radiation options have been exhausted.

Important Safety Information
Contraindications
Do not use Optune in patients with GBM with an implanted medical device, a skull defect (such as, missing bone with no replacement), or bullet fragments. Use of Optune together with skull defects or bullet fragments has not been tested and may possibly lead to tissue damage or render Optune ineffective.

Use of Optune for GBM together with implanted electronic devices has not been tested and may lead to malfunctioning of the implanted device.

Do not use Optune for GBM in patients known to be sensitive to conductive hydrogels. Skin contact with the gel used with Optune may commonly cause increased redness and itching, and may rarely lead to severe allergic reactions such as shock and respiratory failure.

Warnings and Precautions
Optune can only be prescribed by a healthcare provider that has completed the required certification training provided by Novocure.

The most common (≥10%) adverse events involving Optune in combination with chemotherapy in patients with GBM were thrombocytopenia, nausea, constipation, vomiting, fatigue, convulsions, and depression.

The most common (≥10%) adverse events related to Optune treatment alone in patients with GBM were medical device site reaction and headache. Other less common adverse reactions were malaise, muscle twitching, and falls related to carrying the device.

If the patient has an underlying serious skin condition on the treated area, evaluate whether this may prevent or temporarily interfere with Optune treatment.

Do not prescribe Optune for patients that are pregnant, you think might be pregnant or are trying to get pregnant, as the safety and effectiveness of Optune in these populations have not been established.

On December 14, 2020 AnPac Bio-Medical Science Co., Ltd. ("AnPac Bio," the "Company" or "we") (ANPC), a biotechnology company with operations in China and the United States focused on early cancer screening and detection, reported it has made significant progress in detecting pre-cancer diseases (Press release, Anpac Bio, DEC 14, 2020, View Source [SID1234572817]). This development was made via novel sensor design, sensor fabrication, detection process, signal collection, signal processing and proprietary algorithms, which has been validated in both multi-year retrospective and prospective, large sample and population studies. The Company recently completed a prospective large population screening of over 110,000 individuals (and over 150,000 samples throughout this study with some individuals tested multiple times over the years) using AnPac Bio’s Cancer Differentiation Analysis (CDA) technology. The follow-up study involved over ~ 13,000 individuals assessed with high cancer risk, medium cancer risk and low cancer risk using AnPac Bio’s CDA technology.

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Initial results indicated that AnPac Bio CDA technology is capable of providing meaningful information while also screening out pre-cancer diseases, with over 20 types of pre-cancer diseases diagnosed following initial screening utilizing CDA technology and subsequent confirmation by hospital or physical testing center health check-ups. Of the over 20 types of screened out pre-cancer cases, thyroid nodule/tumor ranked number one and pulmonary nodule ranked number two, with about 92.5% confirmed pre-cancer patients in medium to high risk cancer groups. Of the ~ 13,000 individuals, AnPac screened out and confirmed pre-cancer cases at roughly 4.5 times of that of cancer cases, strongly demonstrating that AnPac Bio CDA technology is sensitive to detecting pre-cancer diseases and it could play a critical role in cancer prevention.

Developing a viable pre-cancer and early-stage cancer screening technology has been a long-term goal of global scientists. However, its development and progress has been relatively slow, despite years of heavy investment and efforts by leading scientists and research groups. One of key factors inhibiting breakthroughs in cancer detection has been the lack of previous involvement and contributions of leading semiconductor detection experts (with sensor signal collection and processing).

AnPac Bio consists of research and development team with extensive knowledge and experience in detection technologies including novel and advanced detection technologies including highly sensitive sensor design and fabrications, as well as small signal collection and processing. AnPac’s founder, Dr. Chris Yu, graduated from The Pennsylvania State University with a Ph. D. degree in novel detection technology which involved novel sensor design and fabrication, and small signal detection and processing. Mr. Du, vice president of research and development of AnPac Bio, has ten years of extensive integrated circuit (IC) processing and integration experience, which is critical in fabricating highly sensitive cancer detection sensors, at a New York Stock Exchange traded IC manufacturing company prior to joining AnPac Bio.

AnPac Bio has innovated and developed biophysics based detection technology (in which biophysical properties of blood are detected and analyzed) for pre-cancer disease and early stage cancer screening and detection. The Company is also one of the very first companies to champion multi-cancer detection idea and methodology. The employment of biophysical properties for cancer detection is novel and is an alternative approach to traditional methods, with advantages of being able to detect multiple cancer and pre-cancer types earlier, more cost effective, achieves higher sensitivity and specificity, and has relatively simple sample requirements and test procedures. Specifically, it could play an important role in democratizing cancer screening to large populations at an affordable cost.

Dr. Chris Yu, CEO and Chairman of AnPac Bio commented: "We are very pleased to have achieved this significant breakthrough in successfully detecting pre-cancer diseases, which is critical in cancer prevention and saving lives. From a commercialization perspective, this breakthrough has significant ramifications for market and customer needs, and revenue generation potential. AnPac Bio is very proud to be one of the first research groups to have achieved this important technical milestone, which will significantly expand AnPac Bio’s available market size and customer base, and play an important role in revenue generation for years to come."