On December 21, 2020 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that a Phase 3 trial of XOSPATA (gilteritinib) plus azacitidine versus azacitidine alone in newly diagnosed FLT3 mutation-positive (FLT3mut+) acute myeloid leukemia (AML) patients who were ineligible for intensive induction chemotherapy did not meet its primary endpoint of overall survival at a planned interim analysis of the LACEWING trial (Press release, Astellas, DEC 21, 2020, View Source [SID1234573126]). An independent Data Monitoring Committee recommended terminating the study for futility, concluding results are unlikely to show a statistically significant increase in overall survival. Astellas has stopped enrollment in the trial and is reviewing the results for other action as needed.

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"Although we are disappointed by the primary outcome of LACEWING, we are conducting a thorough review of the data and plan to share detailed results at a later date," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "These results do not affect other ongoing gilteritinib trials. We remain committed to our comprehensive program investigating gilteritinib across a wide range of AML patients with a positive FLT3 mutation, building on gilteritinib’s earlier, positive data in patients with relapsed or refractory FLT3 mutation-positive AML."

AML, a cancer of the blood and bone marrow, is one of the most common types of leukemia in adults.1 It has the lowest survival rate of all types of leukemia.2 Approximately one-third of people with AML have a FLT3 mutation.3,4 This mutation is associated with worsened disease-free survival and overall survival, and a higher risk of getting the disease more than once.3,4,5 Among patients with FLT3mut+ AML, an estimated 30-40 percent are not candidates for intensive chemotherapy regimens because of age, performance status, and/or comorbid conditions.6

On December 21, 2020 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, and City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases, reported that a Phase 1 single-center, two-arm clinical trial has been initiated to establish the safety and feasibility of administering MB-101 (autologous IL13Rα2-CAR T cells) to patients with leptomeningeal brain tumors (e.g., glioblastoma, ependymoma or medulloblastoma) (Press release, Mustang Bio, DEC 21, 2020, View Source [SID1234573176]). The trial will enroll up to 30 patients and take place at City of Hope, where the chimeric antigen receptor T ("CAR T") cell therapy was initially developed.

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All subjects enrolled in the trial will undergo surgery for the placement of an intraventricular (ICV) Rickham catheter for CAR T cell delivery. The Phase 1 trial will establish the safety and feasibility of administering MB-101 through the ICV Rickham catheter over four weekly cycles in patients with glioblastoma (Arm 1) and ependymoma or medulloblastoma (Arm 2). The primary endpoints that will be evaluated are toxicity and survival at three months. Secondary endpoints include overall survival, CAR T and endogenous T cell levels, cytokine levels and phenotype detection in peripheral blood, tumor cyst fluid and cerebrospinal fluid.

Lisa Feldman, M.D., Ph.D., a neurosurgeon and assistant clinical professor in the Division of Neurosurgery at City of Hope and principal investigator of the clinical trial, commented, "Leptomeningeal brain tumors are a form of metastatic brain cancer, which is currently very difficult to treat. We are encouraged by the potential of administering autologous IL13Rα2-CAR T cells intraventricularly to patients with leptomeningeal brain tumors. This CAR T cell therapy has demonstrated early safety and efficacy results in a previous clinical trial conducted at City of Hope, and we believe these preliminary results warrant further evaluation of these CAR T cells. We look forward to providing updates on the trial and to continue working closely with Mustang with the goal of bringing a safe and effective treatment option to patients with this life-threatening disease."

Manuel Litchman, M.D., president and chief executive officer of Mustang, said, "We are pleased to further study MB-101 in leptomeningeal brain tumors as it has already demonstrated therapeutic potential when infused into the ventricular system, including delivering a complete response in a leptomeningeal glioblastoma patient that was published in the New England Journal of Medicine. Our ongoing work with City of Hope continues to advance the research of our CAR T portfolio to bring potential therapies to patients suffering from devastating diseases."

Additional information about the trial can be found on clinicaltrials.gov using the identifier NCT04661384.

About MB‐101 (IL13Rα2‐specific CAR T cells)
IL13Rα2 is an attractive target for CAR T therapy as it has limited expression in normal tissue but is overexpressed on the surface of the majority of malignant glioma cells, including glioblastoma multiforme, ependymoma and medulloblastoma. CAR T cells are designed to express a membrane‐tethered IL‐13 receptor ligand (IL‐13) incorporating a single‐point mutation that provides high affinity for IL13Rα2 and reduces binding to IL13Rα1 in order to reduce healthy tissue targeting. Mustang is developing MB‐101 as an optimized CAR T product incorporating enhancements in CAR design and T cell engineering to improve antitumor potency and T cell persistence. MB‐101 includes a second‐generation hinge optimized CAR containing mutations in the IgG4 linker to reduce off‐target Fc interactions, the 4-1BB (CD137) co‐stimulatory signaling domain for improved persistence of CAR T cells and the extracellular domain of CD19 as a selection/safety marker. To further improve persistence, central memory T cells are enriched and genetically engineered using a manufacturing process that limits ex vivo expansion to reduce T cell exhaustion and maintain a memory T cell phenotype.

On December 21, 2020 AstraZeneca reported that Tagrisso (osimertinib) has been approved in the US for the adjuvant treatment of adult patients with early-stage epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after tumour resection with curative intent (Press release, AstraZeneca, DEC 21, 2020, View Source [SID1234573127]). Tagrisso is indicated for EGFRm patients whose tumours have exon 19 deletions or exon 21 L858R mutations as detected by an approved test.

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The approval was granted under the US Food and Drug Administration’s (FDA) Real-Time Oncology Review (RTOR) pilot program. Five other countries participated in a concurrent submission and review process through FDA’s Project Orbis.

While up to 30% of all patients with NSCLC may be diagnosed early enough to have potentially curative surgery, disease recurrence is still common in early-stage disease and nearly half of patients diagnosed in Stage IB, and over three quarters of patients diagnosed in Stage IIIA, experience recurrence within five years.1-4

The approval was based on results from the ADAURA Phase III trial where Tagrisso demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in the primary analysis population of patients with Stage II and IIIA EGFRm NSCLC, and also in the overall trial population of patients with Stage IB-IIIA disease, a key secondary endpoint.

Roy S. Herbst, MD, PhD, chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, New Haven, CT and principal investigator in the ADAURA Phase III trial, said: "Adjuvant Tagrisso has demonstrated an unprecedented disease-free survival benefit for early-stage lung cancer patients with EGFR mutations who face high rates of recurrence even after successful surgery and subsequent chemotherapy. This approval reinforces how critical it is to test all lung cancer patients for EGFR mutations before deciding how to treat them and regardless of their stage at diagnosis. This will help ensure as many patients as possible can benefit from this potentially practice-changing treatment."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "For the first time, a targeted, biomarker-driven treatment option is available to patients in the US with early-stage EGFR-mutated lung cancer. This approval dispels the notion that treatment is over after surgery and chemotherapy, as the ADAURA results show that Tagrisso can dramatically change the course of this disease. We remain committed to treating cancer patients earlier, when they may still have a chance of being cured."

Adjuvant treatment with Tagrisso reduced the risk of disease recurrence or death by 83% in the primary endpoint of DFS in patients with Stage II and IIIA disease (hazard ratio [HR] 0.17; 95% confidence interval [CI] 0.12-0.23; p<0.0001). DFS results in the overall trial population of patients with Stage IB-IIIA disease showed Tagrisso reduced the risk of disease recurrence or death by 80% (HR 0.20; 95% CI 0.15-0.27; p<0.0001). At two years, 89% of patients treated with Tagrisso remained alive and disease free versus 52% on placebo after surgery, the current standard of care. The safety and tolerability of Tagrisso in this trial was consistent with previous trials in the metastatic setting.

Tagrisso was recently granted Breakthrough Therapy Designation for patients in the early-stage disease setting by the US FDA. In April 2020, an Independent Data Monitoring Committee recommended for the ADAURA trial to be unblinded two years early based on a determination of overwhelming efficacy. Investigators and patients continue to participate in the trial and remain blinded to treatment. The results from the ADAURA trial were presented during the plenary session of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program in May 2020 and were recently published in The New England Journal of Medicine.

The US regulatory submission was reviewed under the FDA’s RTOR pilot program which aims to ensure that safe and effective treatments are available to patients as early as possible. Five national health authorities collaborated with the FDA on this review through Project Orbis, an initiative of the FDA Oncology Center of Excellence, which provides a framework for concurrent submission and review of oncology medicines among international partners. These included Health Canada, the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (Anvisa), Swissmedic, and Singapore Health Sciences Authority. The UK Medicines and Healthcare products Regulatory Agency participated in the review as an observer.

In China, Tagrisso is under priority review for the adjuvant treatment of patients with early-stage EGFRm NSCLC based on the ADAURA Phase III trial. This indication is also under regulatory review in the EU and additional global submission discussions are ongoing.

Tagrisso is a once-daily oral tablet approved for the 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC and for the treatment of locally advanced or metastatic EGFR T790M mutation-positive NSCLC in the US, Japan, China, the EU and many other countries around the world.

Lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.5 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.6 The majority of all NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.1-3

For patients with resectable tumours, the majority of patients eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.4 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.7-8

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.9-11 These patients are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which block the cell-signalling pathways that drive the growth of tumour cells.12

ADAURA
ADAURA is a randomised, double-blinded, global, placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, IIIA EGFRm NSCLC following complete tumour resection and adjuvant chemotherapy as indicated. Patients were treated with Tagrisso 80mg once-daily oral tablets or placebo for three years or until disease recurrence.

The trial enrolled in more than 200 centres across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was DFS in Stage II and IIIA patients and a key secondary endpoint was DFS in Stage IB, II and IIIA patients. The data readout was originally anticipated in 2022. The trial will continue to assess overall survival.

Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system metastases Tagrisso 40mg and 80mg once-daily oral tablets have received approval in the US, Japan, China, the EU and many countries around the world for 1st-line EGFRm advanced NSCLC and EGFR T790M mutation-positive advanced NSCLC.

AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

AstraZeneca aims to address the unmet needs of patients with EGFRm tumours as a genetic driver of disease with the approved medicines Iressa (gefitinib) and Tagrisso, and its ongoing Phase III trials LAURA, NeoADAURA, and FLAURA2.

AstraZeneca is committed to addressing tumour mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD which test Tagrisso in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines.

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 six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – 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 December 21, 2020 Sesen Bio (Nasdaq: SESN), a late-stage clinical company developing targeted fusion protein therapeutics for the treatment of patients with cancer, reported submission of the completed Biologics License Application (BLA) to the FDA for Vicineum for the treatment of high-risk, BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) on December 18, 2020 (Press release, Sesen Bio, DEC 21, 2020, View Source [SID1234573177]).

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Within 60 days after receipt of the completed application, the FDA will issue a decision to the Company on the acceptance of the filing, and whether the BLA has received Priority Review (six-month target PDUFA date) under its existing Fast Track designation.

The BLA is supported by the pivotal Phase 3 VISTA trial, which the Company believes demonstrates a strong benefit-risk profile. The BLA also includes positive chemistry, manufacturing and controls (CMC) data that the Company believes validates the analytical comparability between clinical and commercial supply.

"There remains a significant unmet need for high-risk NMIBC, and we believe the differentiated clinical profile of Vicineum will provide a best-in-class option for physicians and their patients," said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio. "Our strong non-clinical and clinical data, in addition to our positive comparability data, give us confidence in the regulatory path forward. I would like to thank the entire Sesen Bio team and our regulatory and manufacturing partners for their tireless dedication in helping us to complete the BLA submission. We look forward to continuing our regulatory progress by submitting a Marketing Authorization Application in Europe, which we anticipate in early 2021."

Bladder cancer is the sixth most commonly diagnosed cancer in the US, in which approximately 80% of patients are diagnosed with NMIBC. For patients who do not respond to BCG, the recommended option for treatment is radical cystectomy (the complete removal of the bladder) or Keytruda. Results of market research conducted by the Company show that when given the choice between Vicineum and Keytruda, doctors will choose Vicineum over 80% of the time. If approved by the FDA, Vicineum could be a best-in-class treatment option for patients, and a critical step in Sesen Bio realizing its mission to save and improve the lives of patients.

About Vicineum

Vicineum, a locally administered fusion protein, is Sesen Bio’s lead product candidate being developed for the treatment of high-risk non-muscle invasive bladder cancer (NMIBC). Vicineum is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A. Vicineum is constructed with a stable, genetically engineered peptide tether to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical trials conducted by Sesen Bio, EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression observed on normal bladder cells. Sesen Bio is currently conducting the Phase 3 VISTA trial, designed to support the registration of Vicineum for the treatment of high-risk NMIBC in patients who have previously received a minimum of two courses of bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. Additionally, Sesen Bio believes that cancer cell-killing properties of Vicineum promote an anti-tumor immune response that may potentially combine well with immuno-oncology drugs, such as checkpoint inhibitors. The activity of Vicineum in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.

About Non-Muscle Invasive Bladder Cancer

Bladder cancer is the sixth most commonly diagnosed cancer in the United States, and approximately 80 percent of patients have non-muscle invasive bladder cancer (NMIBC). In NMIBC, cancer cells are in the lining of the bladder or have grown into the lumen of the bladder but have not spread into muscle or other tissue. NMIBC primarily affects men and is associated with carcinogen exposure. Initial treatment includes surgical resection; however, there is a high rate of recurrence and more than 60 percent of all patients diagnosed with NMIBC will receive bacillus Calmette-Guérin (BCG) immunotherapy. While BCG is effective in many patients, challenges with tolerability have been observed and many patients will experience recurrence of disease. If BCG is not effective or a patient can longer receive BCG, the recommended option for treatment is radical cystectomy, the complete removal of the bladder.

On December 21, 2020 Peptomyc S.L., a biotech company specialized in the development of protein and peptide therapeutics for cancer treatment, reported that it has officially transitioned from pre-clinical to Clinical Stage, having filed its first Clinical Trial Application in Europe (Press release, Peptomyc, DEC 21, 2020, View Source [SID1234573128]). The company has recently completed the pre-clinical safety studies for its first-in-class MYC inhibitor, OMO103. MYC is an oncoprotein deregulated in most –if not all- types of cancer. Accordingly, OMO103 has demonstrated potent anti-tumor activity in multiple preclinical models of cancer, and is now ready to be tested in Phase I/II clinical studies. The treatment of the first patient with is expected to start in Q1, 2021.

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Manuela Niewel, MD, PhD, as Chief Medical Officer of the company, will assume the responsibility for leading Peptomyc’s clinical development, regulatory and medical affairs activities. "I am really excited about this important step and look forward to seeing OMO103 successfully acting in patients", Dr. Niewel says. " With OMO-103, we will address three major unmet medical needs in the oncology field: Non-Small-Cell Lung Cancer, Triple Negative Breast Cancer, and Colorectal Cancer.

The Phase I dose-escalation will start in three Spanish sites and later, in Phase II, we will expand the study to additional European sites".

Marie-Eve Beaulieu, PhD, co-founder and Chief Scientific Officer of Peptomyc adds: "The demonstration of our product’s quality, safety and stability, clearly represents a key milestone in our efforts to develop potentially life-saving cancer drugs. We are definitely thrilled to continue advancing Myc inhibition towards marketing approval".