On June 7, 2021 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, reported that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted a supplemental Biologics License Application (sBLA) for anti-PD-1 antibody tislelizumab for the treatment of patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors (Press release, BeiGene, JUN 7, 2021, View Source [SID1234583657]).

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"We are excited by the acceptance of our filing for tislelizumab in patients with MSI-H or dMMR solid tumors, which underscores our ongoing commitment to pursuing the full potential of tislelizumab, a potentially differentiated checkpoint inhibitor, and expanding its access where there is unmet medical need. This submission also marks the seventh indication submitted to health authorities, including three approvals for our tislelizumab program," commented Yong (Ben) Ben, M.D., Chief Medical Officer, Immuno-Oncology at BeiGene. "Results from our Phase 2 trial demonstrated that tislelizumab’s treatment effect was consistent and durable across tumor types and endpoints. We are encouraged by the data and plan to continue our communications with the CDE, hoping to bring this medicine to more patients."

The sBLA is supported by clinical results from a single-arm, multi-center, open-label, pivotal Phase 2 clinical trial (NCT03736889) to evaluate efficacy and safety of tislelizumab as monotherapy in patients with previously treated locally advanced unresectable or metastatic MSI-H or dMMR solid tumors, with an enrollment of 80 patients in China. Patients received tislelizumab 200 mg intravenously every three weeks until disease progression, unacceptable toxicity, or withdrawal. Radiological imaging was performed at nine weeks and then every six weeks for the first year of therapy and every 12 weeks thereafter. The primary efficacy analysis set included patients who received any dose of tislelizumab with measurable disease per independent review committee (IRC) at baseline. The primary endpoint of this trial is objective response rate (ORR) as assessed by IRC per RECIST v1.1; secondary endpoints include time to response (TTR), duration of response (DoR), disease control rate (DCR), and progression-free survival (PFS) as assessed by investigator and IRC, overall survival (OS), and safety and tolerability. Results of this study were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

About Microsatellite Instability-High or Mismatch Repair Deficient Solid Tumors

Microsatellite instability-high (MSI-H) cancer cells have a greater than normal number of genetic markers called microsatellites, which are short, repeated sequences of DNA. Cancer cells that have large numbers of microsatellites may have defects in the ability to correct mistakes (also known as mismatch repair deficiency, or dMMR) that occur when DNA is copied in the cell. MSI-H and dMMR tumors are found most often in colorectal cancer and other types of gastrointestinal cancer and endometrial cancer, although they may also be found in cancers of the breast, prostate, bladder and thyroid. i

About Tislelizumab

Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

The China National Medical Products Administration (NMPA) has granted tislelizumab approval in three indications, including full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy; and conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies and for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Full approval for these indications is contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

In addition, four supplemental Biologics License Applications for tislelizumab have been accepted by the Center for Drug Evaluation (CDE) of the NMPA and are under review for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy, for second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy, for patients with previously treated with at least one systemic therapy hepatocellular carcinoma and for patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors.

BeiGene has initiated or completed 17 potentially registration-enabling clinical trials in China and globally, including 13 Phase 3 trials and four pivotal Phase 2 trials.

In January 2021, BeiGene and Novartis entered into a collaboration and license agreement granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

Tislelizumab is not approved for use outside of China.

About the Tislelizumab Clinical Program

Clinical trials of tislelizumab include:

Phase 3 trial comparing tislelizumab with docetaxel in the second- or third-line setting in patients with NSCLC (NCT03358875);
Phase 3 trial comparing tislelizumab to salvage chemotherapy in patients with relapsed or refractory classical Hodgkin Lymphoma (cHL; NCT04486391);
Phase 3 trial in patients with locally advanced or metastatic urothelial carcinoma (NCT03967977);
Phase 3 trial of tislelizumab in combination with chemotherapy versus chemotherapy as first-line treatment for patients with advanced squamous NSCLC (NCT03594747);
Phase 3 trial of tislelizumab in combination with chemotherapy versus chemotherapy as first-line treatment for patients with advanced non-squamous NSCLC (NCT03663205);
Phase 3 trial of tislelizumab in combination with platinum-based doublet chemotherapy as neoadjuvant treatment for patients with NSCLC (NCT04379635);
Phase 3 trial of tislelizumab combined with platinum and etoposide versus placebo combined with platinum and etoposide in patients with extensive-stage small cell lung cancer (NCT04005716);
Phase 3 trial comparing tislelizumab with sorafenib as first-line treatment for patients with hepatocellular carcinoma (HCC; NCT03412773);
Phase 2 trial in patients with previously treated unresectable HCC (NCT03419897);
Phase 2 trial in patients with locally advanced or metastatic urothelial bladder cancer (NCT04004221);
Phase 3 trial comparing tislelizumab with chemotherapy as second-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC; NCT03430843);
Phase 3 trial of tislelizumab in combination with chemotherapy as first-line treatment for patients with ESCC (NCT03783442);
Phase 3 trial of tislelizumab versus placebo in combination with chemoradiotherapy in patients with localized ESCC (NCT03957590);
Phase 3 trial of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment for patients with gastric cancer (NCT03777657);
Phase 2 trial of tislelizumab in patients with relapsed or refractory cHL (NCT03209973);
Phase 2 trial in patients with MSI-H/dMMR solid tumors (NCT03736889); and
Phase 3 trial of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment in patients with nasopharyngeal cancer (NCT03924986).
BeiGene Oncology

BeiGene is committed to advancing best and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines to patients across the globe. We have a growing R&D team of approximately 2,300 colleagues dedicated to advancing more than 90 clinical trials involving more than 13,000 patients and healthy volunteers. Our expansive portfolio is directed by a predominantly internalized clinical development team supporting trials in more than 40 countries. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. The Company currently markets three medicines discovered and developed in our labs: BTK inhibitor BRUKINSA in the United States, China, Canada, and additional international markets; and non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab and PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis Pharma AG granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

On June 7, 2021 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a pioneer in T-cell immunotherapy, leveraging its novel allogeneic EBV T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, reported a combined long-term overall survival (OS) analysis from three clinical studies of tabelecleucel (tab-cel) in patients with Epstein-Barr virus-driven post-transplant lymphoproliferative disease (EBV+ PTLD) after solid organ transplantation (SOT) (Press release, Atara Biotherapeutics, JUN 7, 2021, View Source [SID1234583673]). The results are featured in an oral plenary presentation at the American Transplant Congress (ATC 2021 Virtual Connect), taking place June 4-9, 2021.

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Combined objective response rate (ORR) and OS data across two SOT subgroups – patients relapsed or refractory (R/R) to rituximab monotherapy and patients R/R to rituximab + chemotherapy (CT) – showed one- and two-year OS for patients achieving either complete response (CR) or those achieving partial response (PR). Data presented at ATC 2021 confirm benefit of tab-cel in SOT PTLD and show similar one- and two-year probability of OS irrespective of patients achieving CR or PR (according to Lugano criteria). Treatment response and OS data were assessed from two completed single-arm, Phase 2 studies (95-024, NCT00002663 and 11-130, NCT01498484) and the multi-center expanded access (EAP-201) study (NCT02822495).

"Patients who have received a solid organ transplant such as a new kidney, lung, heart or liver and go on to develop EBV+ PTLD that is relapsed or refractory to rituximab monotherapy or R-chemotherapy face a poor prognosis, with median survival of only about three months," said Jakob Dupont, M.D., Head of Global Research & Development at Atara. "There is a significant unmet need in these patients for whom there are no approved therapies, let alone therapies specifically designed to treat EBV+ PTLD. Combined data from across three clinical studies in SOT recipients with relapsed or refractory disease demonstrated similar long-term survival benefit in those who had either partial or complete response to treatment. These data indicate that tab-cel may help address an urgent unmet need in these patients with high rates of mortality."

Overall Survival (OS) by Best Overall Response (BOR)

All SOT recipients with EBV+ PTLD R/R to rituximab as monotherapy or combined with chemotherapy were treated with tabelecleucel, receiving a median (range) of 2.0 (1-9) cycles

Atara has previously shown benefit in patients with EBV+ PTLD after SOT who responded to tab-cel, including up to 100 percent two-year survival rates1,2. Data presented at EBMT 2021 demonstrated similar results in terms of overall survival in EBV+ PTLD patients who received tab-cel following hematopoietic cell transplantation (HCT).

Safety

Tab-cel was well-tolerated in this immunocompromised population with high disease burden and multiple comorbidities. Notably, there was no emerging safety concern and no instances of tumor flare reaction, infusion-related reactions, graft versus host disease (GvHD), cytokine release syndrome (CRS), neurotoxicity or organ rejection reported in these patients.

"We are excited to see the data presented at ATC 2021 reinforce the clinical benefit in patients who responded to tab-cel, including up to 100 percent two-year survival rates," said Pascal Touchon, President and Chief Executive Officer at Atara. "Atara understands the imperative to provide treatment options for these very sick, treatment-refractory and immunocompromised patients."

Atara Presentation at ATC 2021:

Title: Overall Survival by Best Overall Response with Tabelecleucel in Patients with Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disease after Solid Organ Transplant

Date & Time: Monday, June 7, 2021 at 10:30 a.m. ET

Oral Session & Number: Plenary Oral Abstract Session 3

On June 7, 2021 The Scottish Medicines Consortium (SMC) reported that has accepted POTELIGEO (mogamulizumab) for restricted use by NHS Scotland for the treatment of adults with advanced mycosis fungoides (MF) or Sézary syndrome (SS) (stage ≥IIB MF and all SS) following at least one prior systemic therapy, who are clinically ineligible for or refractory to treatment with brentuximab vedotin (Press release, Kyowa Hakko Kirin, JUN 7, 2021, View Source [SID1234583690]).1

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The ultra-rare blood cancers mycosis fungoides and Sézary syndrome are two subtypes of cutaneous T-cell lymphoma (CTCL).1,2 The medicine was accepted following consideration through the SMC’s Patient and Clinician Engagement (PACE) process, which is used for medicines for end of life and/or ultra-rare conditions.

Richard Johnson, Northern Cluster General Manager, responsible for the UK at Kyowa Kirin, commented: "We are delighted that eligible adults with MF and SS can now access mogamulizumab through NHS Scotland. Today’s advice from the SMC marks an important milestone and is testament to the hard work, collaboration and commitment of the wider CTCL community and the SMC, to ensure those living with these ultra-rare blood cancers have an innovative treatment option in an area of high unmet need."

Dr Pam McKay, Consultant Haematologist and Honorary Clinical Associate Professor at The Beatson – West of Scotland Cancer Centre added: "This is a welcome decision from the SMC which means another treatment option will be available for those living with MF and SS. It has been well documented that those who are at the advanced stages of CTCL have a poor prognosis3 and very few licensed, systemic and well tolerated therapeutic options available to them. Furthermore, those living with CTCL also have a substantially reduced quality of life as the condition causes an immense impact upon their day-to-day functions as well as on the lives of their carers and loved ones. The use of an effective therapy such as mogamulizumab, will be greatly welcomed by adults with MF and SS and clinicians in Scotland, who now have an additional option for those currently living with the effects of this debilitating disease."

MF and SS are two forms of CTCL, which is a serious and potentially life-threatening form of cancer.4 Additionally, there is a significant impact on quality of life for those caring for an individual living with CTCL.5 CTCL is treatable but not curable and there is a clear unmet need for new treatment options.

Ropinder Gill, Chief Executive at Lymphoma Action commented: "This is a hugely significant development for those living in Scotland with these rare haematological cancers. Mogamulizumab offers people with MF and SS a much-needed new treatment option for a disease where, to date, therapies have been limited. Lymphoma Action welcomes this decision by the SMC who have recognized that people with MF and SS should have access to the full range of treatment options."

This decision comes after the National Institute for Health and Care Excellence (NICE) recommended not to reimburse mogamulizumab in England and Wales for the treatment of adult patients with certain types of CTCL, namely MF/SS who have received at least one prior systemic therapy.

Kyowa Kirin lodged an appeal against NICE’s recommendation on 18 March 2021 and appeals were also lodged by Lymphoma Action & Leukaemia Care (joint submission) and the UK Cutaneous Lymphoma Group (UKCLG). The NICE appeal panel convened on 10 May 2021 to hear oral representations from the appellants and a final decision regarding the appeal is expected in July 2021. Kyowa Kirin remains committed to finding a solution for people living with SS/MF to have access to POTELIGEO in England and Wales and will continue to work with NICE and NHS England to find a resolution.

About POTELIGEO (mogamulizumab)

Mogamulizumab is a first-in-class humanised monoclonal antibody (mAb) directed against CC chemokine receptor 4 (CCR4), a protein consistently expressed on cancerous cells seen in both MF and SS;6,7,8 once mogamulizumab binds to CCR4, it increases attraction of immune cells from the immune system to destroy the cancerous cells.9

Mogamulizumab has been shown to offer benefits to many patients with MF and SS.10 The MAVORIC trial compared the efficacy of mogamulizumab with vorinostat in previously treated people with relapsed or refractory mycosis fungoides or Sézary syndrome, two types of Cutaneous T-cell lymphoma (CTCL).10 Patients taking mogamulizumab experienced control over their disease for more than twice as long as those taking the comparator treatment, vorinostat*1 (7.7 months vs 3.1 months of median progression free survival), the primary endpoint of the trial.10 Levels of adverse events were similar between the two treatment groups.10 The MAVORIC trial is the largest in CTCL; it enrolled a total of 372 patients across 61 sites in 11 countries (of which 16 sites were in Europe, including three in England).10

About Mycosis Fungoides (MF) and Sézary Syndrome (SS)

MF and SS are characterised by localisation of cancerous white blood cells called T lymphocytes (T cells), to the skin.11,12 These cancerous T cells consistently express a protein called CC-chemokine receptor 4 (CCR4), which enables them to move from the blood to the skin.6,7,8 When these cancerous T cells move to the skin, they can create a localised inflammatory immune skin response, commonly resulting in visible skin symptoms of red patches or plaques 6,13,14,15,16 which can resemble psoriasis or eczema.11

MF and SS can affect the skin, blood, lymph nodes (part of the body’s immune system which is spread throughout the body) and internal organs.17 All four areas of the body are used to assess disease stage,18,19 and clinically significant involvement of the blood, particularly in more advanced disease, is linked with increased morbidity and an overall reduction in patient survival.18,20,21

CTCL can take, on average, between 2 and 7 years for individuals to receive a confirmed diagnosis.22 It is critical for doctors to consider CTCL as an early differential diagnosis as the patient’s prognosis can be affected if the disease progresses to later stages.23 Whilst most individuals that present with early stage disease do not progress to a more severe stage,24 patients with advanced disease have significantly poorer outcomes with only around half of patients (52%) surviving for just 5 years.18

CTCL is a ultra-rare disease that affects 0.7 per 100,000 patients across the UK.3 The annual incidence of MF in Europe is estimated to be between 1 in 110,000 to 1 in 350,000.25 The annual incidence of SS is 1 in 10,000,000.26 Together they represent approximately 65% of all cases of CTCL.17

*1 Vorinostat is a USA FDA-licensed existing treatment for MF and SS and is currently unlicensed in the EU

On June 7, 2021 Ambrx, a San Diego clinical-stage biotech with operations in Shanghai, reported that it has filed for a US IPO that is expected to raise $100 million (Press release, Ambrx, JUN 7, 2021, View Source [SID1234583791]). Founded in 2003, Ambrx develops antibody-drug conjugates and bispecifics for unmet oncology needs. It builds engineered precision biologics by incorporating synthetic amino acids (SAAs) into proteins within living cells, a technology that offers better efficacy and safety, according to the company. Its lead drug, an ADC candidate, is being tested in a China Phase II/III trial for HER2-positive metastatic breast cancer led by a China partner, NovoCodex Biopharma.

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On June 7, 2021 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage biotechnology company focused on discovering and developing novel small-molecule drugs for the treatment of cancer and other life-threatening diseases, reported final results from the Phase 2 CANTATA study evaluating the company’s glutaminase inhibitor telaglenastat (CB-839) (Press release, Calithera Biosciences, JUN 7, 2021, View Source [SID1234583641]). The findings were highlighted in an oral presentation at the virtual American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting.

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The CANTATA trial evaluated the efficacy and safety of telaglenastat in combination with cabozantinib versus placebo with cabozantinib in patients with advanced or metastatic renal cell carcinoma (RCC) who had been treated with one or two prior lines of systemic therapy, including at least one anti-angiogenic therapy or the combination of ipilimumab and nivolumab.

Results announced previously showed that the addition of telaglenastat to cabozantinib did not improve progression-free survival (PFS) in the study population. Median progression-free survival (mPFS) in patients who received telaglenastat and cabozantinib was 9.2 months versus 9.3 months in patients who received placebo and cabozantinib. The frequency and severity of adverse events in the telaglenastat-treated population were comparable to those of cabozantinib alone and remained consistent with known risks of both agents.

Additional subgroup data was shared today (Abstract 4501), including a pre-specified analysis of CANTATA patients who had received prior immunotherapy that demonstrates patients who received the combination of telaglenastat and cabozantinib had a numerically longer mPFS as compared to patients who received placebo plus cabozantinib (11.1 months versus 9.2 months; HR = 0.77; 95% CI: 0.56, 1.06). Overall survival was not mature at the data cutoff date.

"While we were obviously disappointed by the outcome of the CANTATA study for telaglenastat, we are pleased that the study’s findings may contribute to the growing body of knowledge around efficacy outcomes in patients with RCC," said Susan Molineaux, PhD, president and chief executive officer of Calithera, "It also allowed us to learn more about how telaglenastat may interact with immune checkpoint inhibitors. This is important to us because we are continuing the development of telaglenastat in combination with immune checkpoint inhibitors in a biomarker-selected non-small cell lung cancer population, in the KEAPSAKE clinical study".

The data presentation "CANTATA: Primary analysis of a global, randomized, placebo (Pbo)-controlled, double-blind trial of telaglenastat (CB-839) + cabozantinib versus Pbo + cabozantinib in patients (pts) with advanced/metastatic renal cell carcinoma (mRCC) that progressed on immune checkpoint inhibitor (ICI) or anti-angiogenic therapies" was led by Nizar M. Tannir, MD, FACP, Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Ransom Horne, Jr. Professor for Cancer Research, as part of the virtual "Genitourinary Cancer — Kidney and Bladder" oral session.