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Viracta Announces Positive Phase 1b/2 Data Presented at Oral Presentation on Lead Program for Epstein-Barr Virus (EBV)-associated Relapsed/Refractory Lymphomas at the 2019 American Society of Hematology (ASH) Annual Meeting

On December 8, 2019 Viracta Therapeutics, Inc. (the "Company"), a precision oncology company targeting virus-associated malignancies, reported that its lead investigator, Dr. Pierluigi Porcu of the Sidney Kimmel Cancer Center, Thomas Jefferson University, presented new clinical data from the Company’s Phase 1b/2a clinical trial of the orally administered combination of nanatinostat (Nstat) in combination with the antiviral valganciclovir for the treatment of EBV-associated relapsed/refractory lymphomas (Press release, Viracta Therapeutics, DEC 8, 2019, View Source [SID1234552065]). The data were presented during an oral presentation at the ASH (Free ASH Whitepaper) Annual Meeting in Orlando, Florida.

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The Phase 1b/2a clinical study [NCT03397706] evaluated the combination across three cohorts. Responses were observed across all doses, and in multiple subtypes of lymphomas, including B-cell, T-cell, NK/T-cell and Hodgkin Lymphoma. The recommended Phase 2 dose of the combination was determined, which enabled the Company to proceed with the Phase 2a dose expansion portion of the study. The overall response rate (ORR) in the Phase 1b portion of the study was 56% (10/18), with 28% (5/18) complete response (CR) and a clinical benefit rate (CBR), the sum of ORR plus stable disease rate, of 78% (14/18), with a median duration of treatment for responders of 6.5 months. Two responders remained on treatment for over 12 months, including one patient who remains in complete response at 17 months, following 12.7 months on treatment. In HIV-negative patients, the ORR was 67% (10/15), with a 33% (5/15) CR and a CBR of 93% (14/15).

The combination regimen was well-tolerated, and the most common serious adverse events were hematologic and resolved without sequalae or bleeding events. Notably, no patients discontinued therapy due to a treatment-related adverse event. In the safety data set, the most frequent treatment related grade 3-4 adverse events prior to establishing a recommended Phase 2 dose (RP2D) were thrombocytopenia 25%, neutropenia 20%, and anemia 10%. All patients dosed at the RP2D including additional Phase 2a patients, had an improved hematologic Grade 3-4 safety profile, with low rates of neutropenia (8%) and anemia (8%) and no thrombocytopenia.

"There is a clear unmet medical need for effective and well-tolerated treatment options for EBV-positive lymphomas, and EBV positivity is very often correlated with poor prognosis. The overall objective response rate, complete response rate, and clinical benefit rate observed for heavily pretreated relapsed/refractory EBV-positive lymphoma patients in this dose ranging Phase 1b study are very encouraging, and represent the first reported evidence of substantial clinical efficacy for an EBV-targeting drug combination in EBV-positive lymphomas," said Pierluigi Porcu, MD, Director, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, and Professor of Medical Oncology, Dermatology, and Cutaneous Biology, at the Sidney Kimmel Cancer Center – Jefferson Health (SKCC). "The Phase 1b portion of the study also established a recommended Phase 2 dose and schedule, which is associated with a very low rate of Grade 3/4 adverse events. Preliminary results from the ongoing Phase 2 dose expansion appear to be consistent with those observed in the intermittent dose cohort of the Phase 1b study."

"These data underscore the potential for Nstat and valganciclovir as a novel therapeutic approach for the treatment of relapsed/refractory EBV-positive lymphomas. Moreover, while a biomarker diagnostic test for EBV already exists, it has not been routinely used, given the absence of an effective targeted therapy for EBV-positive lymphomas. Our goal is that our therapy will lead to increased screening of relapsed/refractory lymphomas for the presence of EBV," said Ivor Royston, MD, President and Chief Executive Officer of Viracta. "We expect to complete the Phase 2 portion of the Phase 1b/2 study in the first half of 2020, initiate a registration study in the second half of the year, and expand our treatment approach into EBV-positive solid tumor indications."

Details of the ASH (Free ASH Whitepaper) presentation are as follows:

Title: Combination of Oral Nanatinostat (Nstat), a Novel Histone Deacetylase Inhibitor (HDACi), and the Oral Anti-Viral, Valganciclovir (VGCV), Is Active in Relapsed/Refractory (R/R) Epstein-Barr Virus (EBV)-Positive B-Cell, T-Cell, and Hodgkin Lymphoma: Interim Safety and Efficacy Results from a Phase 1b/2a Study (Abstract # 465)
Presenter: Pierluigi Porcu, MD, Thomas Jefferson University
Session: Hodgkin Lymphoma and T/NK Cell Lymphoma – Clinical Studies: Novel Therapies in Peripheral T-cell Lymphomas
Date/Time: Sunday, December 8, 2019, 12:30 PM
Location: Orange County Convention Center, Orlando, FL, Valencia D (W415D)
The presentation from the 2019 ASH (Free ASH Whitepaper) Annual Meeting can be accessed by visiting the "News/Media" section of the Viracta website: View Source

Viracta has received Fast Track designation from the FDA for its proprietary investigational drug, nanatinostat, in combination with valganciclovir, in relapsed/refractory lymphomas, as well as Orphan Drug Designation for the treatment of post-transplant lymphoproliferative disorder, plasmablastic lymphoma, and angioimmunoblastic T-cell lymphoma.

About Nanatinostat
Nanatinostat (VRx-3996) is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class 1 HDACs which is key to inducing latent viral genes in EBV-associated malignancies. The nanatinostat and valganciclovir combination is being investigated in EBV-associated lymphomas in an ongoing Phase 2 clinical trial [NCT03397706].

About EBV-Associated Cancers
Approximately 95% of the world’s adult population is infected with Epstein-Barr virus (EBV). Infections are commonly asymptomatic. Following infection, the virus remains latent in a small subset of lymphatic cells for the duration of the patient’s life. Under certain circumstances, such cells may undergo malignant transformation and become lymphoma. In addition to lymphomas, EBV is associated with a variety of solid tumors, including nasopharyngeal carcinoma and gastric cancer.

First Clinical Data for REGN5458 (BCMAxCD3) Show Positive Preliminary Results in Multiple Myeloma

On December 8, 2019 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported initial clinical data for REGN5458, a BCMAxCD3 bispecific antibody, in patients with relapsed or refractory (R/R) multiple myeloma (Press release, Regeneron, DEC 8, 2019, View Source [SID1234552066]). BCMA (B-cell maturation antigen) is a protein that is typically over-expressed on multiple myeloma cells. REGN5458 is designed to bind to BCMA on multiple myeloma cells and the CD3 receptor on T-cells, bridging them together and activating T-cell killing of the cancer cell.

Results were presented today at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from the first two dose groups (3 mg and 6 mg weekly doses). Patients had a median of seven lines of prior systemic therapy, and all had failed CD38 antibody treatment. Responses were observed in 4 of 7 (57%) patients, including 3 of 4 (75%) in the 6 mg dose group. In the 6 mg dose group, 2 patients (50%) were also minimal residual disease (MRD) negative, meaning that no cancer cells were detectable in their bone marrow.

"We are encouraged to see promising, rapid clinical activity even at the initial two doses of REGN5458 in heavily pretreated patients with multiple myeloma. Two patients achieved the high bar of MRD negativity, and another patient attained a very good partial response despite entering the trial with difficult-to-treat plasmacytomas outside of the bone marrow," said Israel Lowy, M.D., Ph.D., Senior Vice President and Head of Clinical and Translational Sciences for Oncology at Regeneron. "We are actively recruiting patients into higher dose groups in this trial and look forward to sharing further results in 2020. In addition, we have also initiated a clinical trial for our second BCMAxCD3 bispecific, REGN5459, which has different binding characteristics."

REGN5458 and REGN5459 were invented using Regeneron’s next generation VelocImmune "human antibody mouse" technology, together with its VelociBi platform. These allow for the creation of bispecific antibodies that closely resemble natural human antibodies with no linkers or artificial sequences. Additionally, Regeneron bispecifics are manufactured using similar approaches used for human antibody medicines, with similar pharmacokinetics.

As of data cutoff, there have been no neurotoxicity, dose-limiting toxicities or treatment discontinuations due to adverse events (AEs). The most common treatment-emergent AEs were lymphopenia (n=5), anemia (n=4) and thrombocytopenia and cytokine release syndrome (n=3 each). Grade 3 or higher treatment-emergent AEs were seen in 5 patients and included lymphopenia (n=3), hypertension (n=2) and anemia, atrial fibrillation, fatigue, febrile neutropenia, pain in extremity, septic shock and thrombocytopenia (n=1 each).

Multiple myeloma is the second most common blood cancer, with approximately 32,000 and 138,500 new diagnoses in the U.S. and world respectively. It is characterized by the proliferation of cancerous plasma cells (multiple myeloma cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Recent advances, such as CD38 antibody treatment, have increased life expectancy of patients from 3-4 years to 7-8 years. Despite this, multiple myeloma remains incurable, and most patients will experience relapse and require additional therapy.

The REGN5458 data follow other positive results from Regeneron’s growing bispecific pipeline, including updated REGN1979 data that will be presented at ASH (Free ASH Whitepaper). REGN1979 is an investigational CD3 bispecific that is being studied in R/R follicular lymphoma and diffuse large B-cell lymphoma, including in patients whose cancer did not respond to CAR-T therapy. Regeneron has also invented a second class of CD28 bispecifics, called co-stimulatory bispecifics, which have recently entered clinical trials.

About the REGN5458 Phase 1/2 Dose-escalation Trial
REGN5458 monotherapy is being investigated in an open-label, Phase 1/2 dose-escalation trial in patients with R/R multiple myeloma who have exhausted all therapeutic options, including proteasome inhibitors, immunomodulatory drugs and CD38 antibody treatments. The Phase 1 portion is assessing safety, tolerability and dose-limiting toxicities. Beyond the initial dose groups presented at ASH (Free ASH Whitepaper), additional dose groups are being evaluated to determine a recommended Phase 2 dose regimen. The Phase 2 portion will further assess REGN5458 anti-tumor activity and safety.

Among the patients being enrolled are those with heavily pre-treated multiple myeloma, including those with extra-medullary (outside of the bone marrow) and non-secretory disease (do not secrete detectable myeloma proteins).

In multiple myeloma clinical trials, treatment effectiveness is typically assessed by overall response rate (ORR; with response types categorized by the level of reduction in myeloma protein) and the rate of conversion to negative MRD (which measures the eradication of myeloma cells in bone marrow). For ORR, myeloma protein levels in the blood are reduced by more than 50% in partial responses (PR) and 90% in very good PR (VGPR), while complete responses are defined as no evidence of myeloma protein and ≤5% of plasma cells in the bone marrow. MRD is measured separately from ORR, and MRD negativity is defined as the absence of myeloma cells within 100,000 bone marrow cells.

About the Regeneron Bispecific Antibody Platform
All of Regeneron’s bispecific antibodies are designed to closely resemble natural human antibodies. They are derived from a next-generation version of Regeneron’s proprietary VelocImmune technology and created using the company’s VelociBi platform.

There are six Regeneron investigational bispecific antibodies currently in ongoing clinical trials for multiple blood cancers and solid tumors. These bispecifics fall into three categories:

— CD3 bispecifics are designed to bridge T-cells and tumor cells. At the tumor site, they activate T-cells via their CD3 receptors and promote T-cell killing of the cancer cells. Investigational candidates include:

CD20xCD3 (REGN1979) for non-Hodgkin B-cell lymphomas;
Two distinct BCMAxCD3s (REGN5458 and REGN5459) for multiple myeloma;
MUC16xCD3 (REGN4018) for ovarian cancer.
— CD28 costimulatory bispecifics are also designed to bridge T-cells and tumor cells. At the tumor site, they costimulate T-cells via their CD28 receptors and may synergize with PD-1 inhibitors and/or CD3 bispecifics. Investigational candidates include:

PSMAxCD28 (REGN5678) in combination with Libtayo (cemiplimab) for prostate cancer.
— Tumor-targeted bispecifics are designed to target proteins only on the cancer cell. In this way, they may affect various signaling pathways to hamper the cancer cells’ ability to survive and proliferate. Investigational candidates include:

METxMET (REGN5093) for non-small cell lung cancer that is driven by MET mutations and/or amplifications. REGN5093 targets two different parts of the MET receptor on cancer cells to degrade the receptor and block its ability to trigger cell proliferation.
Regulatory Status of Oncology Programs
REGN1979, REGN5458, REGN5459, REGN4018, REGN5678, REGN5093 and Libtayo are currently under clinical development for the diseases noted in this press release, and their safety and efficacy have not been evaluated by any regulatory authority for these diseases. As part of a global collaboration agreement, Regeneron and Sanofi are jointly developing Libtayo, as well as Regeneron’s BCMAxCD3 and MUC16xCD3 bispecific programs.

Libtayo is approved in the U.S. for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation, and in other countries for similar indications. In the U.S., the generic name for Libtayo is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.

Blueprint Medicines Announces Initial Data from Phase 2 PIONEER Trial of Avapritinib
in Patients with Indolent Systemic Mastocytosis Showing Activity at All Dose Levels Tested

On December 8, 2019 Blueprint Medicines Corporation (NASDAQ:BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported initial data from the Phase 2 PIONEER clinical trial of avapritinib in patients with indolent systemic mastocytosis (SM). Initial data from the dose-finding Part 1 of the PIONEER trial showed rapid and robust reductions in serum tryptase, a well-established measure of mast cell burden, in patients treated with 25 mg, 50 mg or 100 mg of avapritinib once daily (QD). All dose levels of avapritinib tested were well-tolerated, and no patients discontinued treatment due to an adverse event (AE). The results will be presented today in a poster presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, Florida.

Nearly all cases of SM, a rare mast cell disorder, are driven by the KIT D816V mutation, which aberrantly activates mast cells. Patients across all disease subtypes including indolent SM experience debilitating symptoms across multiple organ systems, while advanced SM is uniquely characterized by organ damage due to mast cell infiltration. Avapritinib, an investigational drug, is a highly potent and selective inhibitor of D816V mutant KIT.

"Patients with indolent SM often experience debilitating symptoms, including unpredictable hypersensitivity reactions and anaphylaxis, despite available symptom-directed treatments, leading to reduced quality of life, social isolation and frequent utilization of the healthcare system," said Cem Akin, M.D., Ph.D., Professor of Medicine at the University of Michigan and an investigator on the PIONEER trial. "The initial PIONEER data announced today are highly encouraging and show that low doses of avapritinib are well-tolerated and reduce elevated levels of tryptase in the blood. We believe this early indicator of mast cell response is predictive of reductions in clinical symptoms, which we hope to see confirmed with additional data from the PIONEER trial next year."

"The PIONEER data in patients with indolent SM further highlight the potential of avapritinib, a highly potent inhibitor of D816V mutant KIT, to become a new standard of care across all subtypes of SM," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "Blueprint Medicines is committed to advancing a comprehensive clinical development program for avapritinib, with the goal of bringing a highly effective precision therapy to a broad population of patients with SM."

Blueprint Medicines plans to report additional data from Part 1 of the PIONEER trial that will inform the selection of a recommended Part 2 dose (RP2D), including the change in patient-reported disease symptoms as measured by the Indolent SM Symptom Assessment Form (ISM-SAF), in the first quarter of 2020. The registration-enabling Part 2 of the PIONEER trial is anticipated to initiate patient screening in the first half of 2020.

Highlights from the ASH (Free ASH Whitepaper) Presentation of PIONEER Trial Data in Indolent SM

The dose-finding Part 1 of the PIONEER trial was designed to test three doses of avapritinib (25 mg, 50 mg and 100 mg QD) versus placebo to determine a RP2D. Major eligibility criteria included adults with indolent SM confirmed by central pathology review and moderate to severe symptom burden, despite best available supportive care medications. Across four concurrent cohorts, 39 patients were enrolled, including 10 patients in each avapritinib dose cohort and nine patients in the placebo cohort. As of a data cutoff date of November 12, 2019, the enrolled population had a median time on study of 12 weeks (range: 1-30 weeks).

Baseline Patient Characteristics

At baseline, all patients had symptomatic disease despite best available therapy. Median ISM-SAF total symptom score (TSS) was 52 [range: 19-100 (total possible range: 0-110)]. Patients were taking a median of three medications (range: 1-7) to treat their disease. Mean serum tryptase was 84 micrograms per liter.

Clinical Activity Data

Across all avapritinib dose cohorts, reductions in serum tryptase were robust, occurred rapidly and were sustained in patients treated up to 30 weeks. The placebo cohort showed no change in serum tryptase at 12 weeks.

Tryptase is an enzyme released by activated mast cells. Elevated tryptase in blood serum is a hallmark of SM and a component of the World Health Organization diagnostic criteria. Reduction in serum tryptase is a component of the IWG-MRT-ECNM response criteria (IWG criteria) for advanced SM.

Safety Data

All doses of avapritinib tested were well-tolerated, and most reported AEs were Grade 1 or 2. There were no reported cases of intracranial bleeding, thrombocytopenia or anemia. Across all avapritinib cohorts, five patients (16.7 percent) had Grade 3 AEs, and no patients had serious AEs. In patients treated with placebo, two patients (22.2 percent) had Grade 3 AEs, and two patients (22.2 percent) had serious AEs. There was one Grade 3 cognitive effect reported in the 100 mg cohort. The event resolved following dose modification, and the patient remained on therapy as of the data cutoff date. No patients discontinued treatment due to an AE.

Top-line EXPLORER Trial Data and NDA Submission Plan for Avapritinib in Advanced SM

Blueprint Medicines plans to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for avapritinib for the treatment of patients with advanced SM in the first quarter of 2020. The planned NDA will include response data for approximately 55 patients and safety data for approximately 100 patients from the EXPLORER trial and the PATHFINDER trial.

Blueprint Medicines reported top-line results from the EXPLORER trial. The company plans to report top-line data from the PATHFINDER trial in the first quarter of 2020 and expects these data will be generally consistent with the top-line EXPLORER data.

As of a data cutoff of August 30, 2019, top-line efficacy data from the EXPLORER trial showed a centrally confirmed overall response rate (ORR) of 77 percent in 48 patients evaluable for response per the modified IWG criteria. ORR was defined as complete remission with full or partial recovery of peripheral blood counts, partial remission or clinical improvement. Median duration of response (DOR) and median overall survival were not reached. Median follow-up was 21 months, with patients receiving ongoing treatment up to approximately 3.5 years.

The top-line safety results were generally consistent with previously reported data. In 80 patients evaluable for safety as of the data cutoff date, avapritinib was generally well-tolerated with most AEs reported by investigators as Grade 1 or 2. Across all grades, the most common treatment-emergent AEs reported by investigators were periorbital edema, anemia, diarrhea, fatigue, peripheral edema, nausea, thrombocytopenia, vomiting and cognitive effects. Only six patients discontinued due to treatment-related adverse events.

As of the data cutoff date, no new intracranial bleeding events had been observed in the EXPLORER trial since the company previously presented data at the 24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper). After the data cutoff date, one patient with SM and an associated hematologic neoplasm (SM-AHN) of myelodysplastic syndrome had a Grade 5 intracranial bleed. At the time of the bleeding event, the patient had severe thrombocytopenia and experienced a serious injury involving head trauma.

Investor Event and Webcast Information

Blueprint Medicines will host an investor event on Sunday, December 8, 2019 beginning at 8:30 p.m. ET in Orlando to review initial data from the PIONEER trial. The event will be webcast live and can be accessed under "Events and Presentations" in the Investors & Media section of Blueprint Medicines’ website at View Source A replay of the webcast will be available approximately two hours after the event and will be available for 30 days following the event.

About the Clinical Development Program for Avapritinib in SM

Blueprint Medicines is pursuing a broad clinical development program for avapritinib across advanced, indolent and smoldering forms of SM. Avapritinib is currently being evaluated in three ongoing, registration-enabling clinical trials for SM: the EXPLORER trial, the PATHFINDER trial and the PIONEER trial.

The EXPLORER trial is an open-label, single-arm trial designed to identify the RP2D and demonstrate proof-of-concept in patients with advanced SM. Key trial endpoints include ORR, DOR, quantitative measures of mast cell burden, patient-reported outcomes and safety. The EXPLORER trial has completed patient enrollment.

The PATHFINDER trial is an open-label, single-arm registration-enabling trial designed to confirm the clinical activity of avapritinib in approximately 60 patients with advanced SM. Key trial endpoints include ORR, DOR, quantitative measures of mast cell burden, patient-reported outcomes and safety. Patient enrollment is ongoing at sites in the United States, Canada and European Union.

The PIONEER trial is a randomized, double-blind, placebo-controlled, registration-enabling trial in approximately 112 patients with indolent and smoldering SM. The trial includes three parts: dose-finding Part 1, registration-enabling Part 2 and long-term treatment Part 3. All patients who complete Parts 1 or 2 will have an opportunity to continue to receive treatment with avapritinib in Part 3. Key trial endpoints include the change in patient-reported disease symptoms as measured by the ISM-SAF TSS, quantitative measures of mast cell burden and safety. Part 1 has completed patient enrollment. Part 2 is anticipated to initiate patient screening in the first half of 2020 at sites in the United States, Canada and European Union.

SM patients and clinicians interested in ongoing or planned clinical trials can contact the Blueprint Medicines study director at [email protected] or 1-617-714-6707. Additional details are available at www.pathfindertrial.com, www.pioneertrial.com or www.clinicaltrials.gov.

About SM

SM is one disease driven by the KIT D816V mutation. The majority of patients have indolent SM with symptoms that range from burdensome to life-threatening. A minority of patients have advanced SM, which encompasses a group of high-risk SM subtypes, including aggressive SM (ASM), SM-AHN and mast cell leukemia (MCL), which are associated with organ damage due to mast cell infiltration and poor overall survival. In nearly all SM patients, the KIT

D816V mutation aberrantly activates mast cells. Aberrant mast cell activation and proliferation results in chronic, severe and often unpredictable symptoms, such as pruritus, flushing, headaches, bone pain, nausea, vomiting, diarrhea, anaphylaxis, abdominal pain and fatigue. Currently, there are no approved therapies that selectively inhibit D816V mutant KIT.

About Avapritinib

Avapritinib is an investigational, oral precision therapy that selectively and potently inhibits KIT and PDGFRA mutant kinases. It is a type 1 inhibitor designed to target the active kinase conformation; all oncogenic kinases signal via this conformation. Avapritinib has demonstrated broad inhibition of KIT and PDGFRA mutations associated with gastrointestinal stromal tumors (GIST), including potent activity against activation loop mutations that are associated with resistance to currently approved therapies.

Blueprint Medicines is initially developing avapritinib for the treatment of advanced GIST, advanced SM, and indolent and smoldering SM. The FDA has granted Breakthrough Therapy Designation to avapritinib for two indications: one for the treatment of unresectable or metastatic GIST harboring the PDGFRA D842V mutation and one for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.

BeiGene Announces Clinical Data on BRUKINSA™ (Zanubrutinib) at the 61st American Society of Hematology (ASH) Annual Meeting

On December 8, 2019 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported clinical data from three trials of its BTK inhibitor BRUKINSA (zanubrutinib) were presented at the 61stAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, FL (Press release, BeiGene, DEC 8, 2019, View Source [SID1234552052]). In two oral presentations of BRUKINSA in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), the drug candidate demonstrated consistent safety and a high overall response rate (ORR); in the poster presentation of BRUKINSA combined with BeiGene’s investigational anti-PD-1 antibody tislelizumab in patients with previously treated B-cell malignancies, the combination treatment showed preliminary efficacy and was generally well tolerated.

"The data presented today showing clinical activity and tolerability of BRUKINSA in patients with CLL or SLL are promising for its potential use in patients living with these cancers," said Constantine S. Tam, M.D., Disease Group Lead for Low Grade Lymphoma and Chronic Lymphocytic Leukemia at the Peter MacCallum Cancer Center and Director of Hematology at St. Vincent’s Hospital, Australia. "BTK inhibitors have become an important standard of care for B-cell malignancies, offering the potential for durable responses with manageable safety profiles. It’s encouraging to have more evidence that zanubrutinib can be effective in treating CLL or SLL, including in patients with del(17p) who typically have a worse prognosis and few treatment options."

"The results presented today on BRUKINSA, a BTK inhibitor designed to maximize target occupancy and minimize off-target binding, demonstrated robust clinical activity and a safety profile consistent with what we’ve observed to date in our clinical trials, including safety data that supported the recent U.S. FDA accelerated approval in patients with previously treated mantle cell lymphoma," said Jane Huang, M.D., Chief Medical Officer, hematology at BeiGene. "CLL or SLL is the most common type of leukemia in adults, and despite the advancements of BTK inhibitor therapy for these cancers, there remains a need for highly selective BTK inhibitors capable of promoting long-term responses, and with a safety profile that is tolerable over time. The results presented here today further demonstrate the potential for BRUKINSA to help people living with these persistent, life-threatening cancers."

Initial Results from SEQUOIA Trial Arm C in Treatment-Naïve (TN) CLL or SLL Patients with Del(17p)

Presentation 499

Initial results from Arm C in the open-label, Phase 3 SEQUOIA trial (NCT03336333) of BRUKINSA as a monotherapy demonstrated a high ORR in patients with TN CLL or SLL whose tumor exhibits the deletion of chromosome 17p13.1 [del(17p)]. The safety profile was consistent with that observed in previous clinical trials of BRUKINSA in B-cell malignancies. At the data cutoff of August 7, 2019, with a median follow-up of 10 months, initial results included:

The ORR was 92.7% (101/109); the partial response (PR) rate was 78.9% (86/109); the PR rate with lymphocytosis was 11.9% (13/109); and the complete response (CR) rate was 1.9% (2/109); only four cases of disease progression occurred;

36.7% of patients (40/109) experienced at least one grade ≥3 adverse event (AE) and only one patient discontinued treatment due to AEs;

The most common grade ≥3 AEs, occurring in more than two patients, were neutropenia (10.1%), pneumonia (3.7%) and hypertension (2.8%);

23.9% of patients (26/109) experienced at least one serious AE; and

One patient experienced a fatal AE, pneumonia leading to sepsis and death, which was considered related to treatment drug by the study investigator.
Updated Results from a Phase 1/2 Trial in Patients with CLL or SLL

Presentation 500

Updated results from the open-label, dose-escalation, single-arm, global Phase 1/2 trial (NCT02343120) showed that BRUKINSA was generally well-tolerated and active in patients with relapsed/refractory (R/R) or TN CLL/SLL, irrespective of del(17p) status (n=123; 101 R/R, 22 TN). At the data cutoff of May 8, 2019, with a median follow-up of 29.5 months, results included:

The ORR was 95.9% (118/123); the PR rate was 73.2% (90/123); the PR rate with lymphocytosis was 6.5% (8/123); the CR rate was 16.3% (20/123), including one patient who achieved a CR with incomplete bone marrow recovery;

The median duration of treatment was 25.8 months and 80% of patients (98/123) remained on study treatment; two-year progression-free survival (PFS) was 91% in R/R patients and 95% in TN patients;

61.8% of patients (76/123) experienced at least one grade ≥3 AE and only five patients discontinued treatment due to AEs;

The most common AEs (≥ 20%) were contusion (47.2%), upper respiratory tract infection (42.3%), diarrhea (31.7%), cough (29.3%), headache (23.6%), and fatigue (20.3%);

47.2% of patients (58/123) experienced at least one serious AE; and

One patient experienced a fatal AE, neoplasm-malignant recurrent squamous cell carcinoma, considered unrelated to treatment drug by the study investigator.
BRUKINSA in Combination with PD-1 Inhibitor Tislelizumab in Patients with Previously Treated B-Cell Lymphoid Malignancies

Presentation 1594

Preliminary findings from the open-label, multicenter, Phase 1b trial (NCT02795182) showed that BRUKINSA in combination with the investigational anti-PD-1 antibody tislelizumab demonstrated a generally manageable toxicity profile in patients with R/R B-cell malignancies. A total of 70 patients enrolled in the trial, including 54 patients with aggressive non-Hodgkin’s lymphomas (NHLs) which consist of diffuse large B-cell lymphoma, transformed follicular lymphoma, Richter’s transformation, and central nervous system (CNS) lymphoma. At the data cutoff of August 31, 2019, with a median follow-up of 8.1 months, preliminary findings included:

Of the 54 patients with aggressive NHLs, the ORR was 37.0% (20/54); the PR rate was 20.4% (11/54); the CR rate was 16.7% (9/54); stable disease (SD) rate was 9.3% (5/54);

71.4% of patients (50/70) experienced at least one grade ≥3 AE and 14.3% of patients (10/70) discontinued BRUKINSA and/or tislelizumab treatment due to AEs;

The most common grade ≥3 AEs were neutropenia (12.9%), anemia (10.0%), thrombocytopenia (7.1%), pneumonia (5.7%), neutrophil count decreased (5.7%), tumor lysis syndrome (4.3%), sepsis (4.3%), immune-mediated enterocolitis (4.3%), hypertension (4.3%), lymphocyte count decreased (2.9%), hemolytic transfusion reaction (2.9%), febrile neutropenia (2.9%), back pain (2.9%), acute kidney injury (2.9%), abscess limb (2.9%), and abdominal pain (2.9%);

Grade ≥3 immune-related AEs (irAEs) were reported in 15.7% of patients (11/70) with immune-mediated enterocolitis (4.3%), and pneumonitis (2.9%) occurring in more than one patient; and

Five patients experienced fatal AEs, four of which in the setting of progressive disease were considered unrelated to treatment including multi-organ dysfunction, septic shock and pneumonia, respiratory failure, and aspiration pneumonia, and one of toxic epidermal necrolysis which was considered related to treatment by the study investigator.
About BRUKINSA (zanubrutinib)

BRUKINSA (zanubrutinib) is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad pivotal clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. BRUKINSA was granted accelerated approval by the U.S. FDA to treat adult patients with MCL who have received at least one prior therapy in November 2019. This accelerated approval is based on overall response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

New Drug Applications (NDAs) in China for relapsed refractory (R/R) MCL and R/R chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have been accepted by the China National Medical Products Administration (NMPA) and granted priority review and are pending approval.

BRUKINSA is not approved for use outside the United States. BRUKINSA is not approved for the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma.

IMPORTANT SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher bleeding events including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 2% of patients treated with BRUKINSA monotherapy. Bleeding events of any grade, including purpura and petechiae, occurred in 50% of patients treated with BRUKINSA monotherapy.

Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 23% of patients treated with BRUKINSA monotherapy. The most common Grade 3 or higher infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (27%), thrombocytopenia (10%) and anemia (8%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy.

Monitor complete blood counts during treatment and treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 9% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was skin cancer (basal cell carcinoma and squamous cell carcinoma of skin), reported in 6% of patients. Advise patients to use sun protection.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter have occurred in 2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 0.6% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for at least 1 week after the last dose. Advise men to avoid fathering a child during treatment and for at least 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

The most common adverse reactions in > 10% of patients who received BRUKINSA were neutrophil count decreased (53%), platelet count decreased (39%), upper respiratory tract infection (38%), white blood cell count decreased (30%), hemoglobin decreased (29%), rash (25%), bruising (23%), diarrhea (20%), cough (20%), musculoskeletal pain (19%), pneumonia (18%), urinary tract infection (13%), hematuria (12%), fatigue (11%), constipation (11%), and hemorrhage (10%). The most frequent serious adverse reactions were pneumonia (11%) and hemorrhage (5%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with moderate or strong CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

INDICATION

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Please see full Prescribing Information at beigene.com/PDF/BRUKINSAUSPI.pdf and Patient Information at beigene.com/PDF/BRUKINSAUSPPI.pdf

About the Zanubrutinib Clinical Trial Program

Clinical trials of zanubrutinib include:

Fully-enrolled Phase 3 ASPEN clinical trial in patients with Waldenström macroglobulinemia (WM) comparing zanubrutinib to ibrutinib (NCT03053440), currently the only approved BTK inhibitor for WM;

Phase 3 SEQUOIA trial comparing zanubrutinib with bendamustine plus rituximab in patients with treatment-naive (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (NCT03336333);

Phase 3 ALPINE trial comparing zanubrutinib to ibrutinib in patients with relapsed/refractory (R/R) CLL/SLL (NCT03734016);

Phase 2 trial in combination with GAZYVA (obinutuzumab) in patients with R/R follicular lymphoma (FL) (NCT03332017);

Phase 3 trial comparing zanubrutinib and rituximab to bendamustine and rituximab in patients with untreated MCL (NCT04002297);

Phase 2 MAGNOLIA trial in patients with R/R marginal zone lymphoma (MZL) (NCT03846427);

Phase 2 ROSEWOOD trial (NCT03332017) in China comparing obinutuzumab and zanubrutinib vs obinutuzumab alone in treating patients with R/R FL;

Completed Phase 2 trials in patients with R/R MCL (NCT03206970) and R/R CLL/SLL (NCT03206918); and

Completed enrollment in Phase 2 clinical trial in patients with WM (NCT03332173).
About Tislelizumab

Tislelizumab (BGB-A317) is an investigational 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 candidate produced from BeiGene’s immuno-oncology biologics program and is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

Select ongoing clinical trials of tislelizumab include a Phase 3 clinical trial in patients with second-line or third-line non-small cell lung cancer (NSCLC); a Phase 3 clinical trial in first-line patients with hepatocellular carcinoma (HCC); a Phase 3 clinical trial in second-line patients with esophageal squamous carcinoma (ESCC); a Phase 3 clinical trial in first-line patients with gastric cancer (GC); a Phase 3 clinical trial in first-line patients with ESCC; and a Phase 2 clinical trial in second- or third-line patients with HCC. The aforementioned trials are enrolling patients in multiple countries, including the United States, Europe, and China.

In addition to a pivotal Phase 2 clinical trial in patients with relapsed or refractory (R/R) classical Hodgkin’s lymphoma (cHL) and a pivotal Phase 2 clinical trial in patients with locally advanced or metastatic urothelial cancer, BeiGene is conducting a Phase 3 clinical trial in first-line patients with non-squamous NSCLC; a Phase 3 clinical trial in first-line patients with squamous NSCLC; a Phase 3 clinical trial in patients with first-line nasopharyngeal cancer (NPC); a Phase 3 clinical trial in first-line patients with urothelial carcinoma (UC); a Phase 3 clinical trial in patients with localized ESCC; and a Phase 2 trial in patients with MSI-H or dMMR solid tumors. These studies have been enrolling patients primarily in China.

New drug applications (NDA) for tislelizumab in patients with R/R cHL and in patients with previously treated locally advanced or metastatic UC have been accepted and granted priority review by the China National Medical Products Administration (NMPA, formerly known as CFDA). BeiGene has full development and commercial rights to tislelizumab worldwide.

Karyopharm Presents XPOVIO® (Selinexor) and Eltanexor Data at the American Society of Hematology 2019 Annual Meeting

On December 8, 2019 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), an oncology-focused pharmaceutical company, reported that four posters relating to XPOVIO (selinexor), the Company’s first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, and eltanexor, its next generation SINE compound, will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2019 Annual Meeting taking place December 7-10, 2019 in Orlando (Press release, Karyopharm, DEC 8, 2019, View Source [SID1234552038]). The four posters include: updated data from the Kyprolis (carfilzomib) arm of the Phase 1b/2 STOMP study evaluating selinexor in combination with backbone therapies in patients with relapsed or refractory multiple myeloma; new data from the Revlimid (lenalidomide) plus selinexor arm of the STOMP study evaluating this combination in patients with newly diagnosed multiple myeloma; encore data highlighting the previously disclosed comparison of patients in the STORM study, Karyopharm’s Phase 2b study evaluating XPOVIO in patients with heavily pretreated, triple class refractory multiple myeloma, to matched patients from the MAMMOTH study; and new Phase 1/2 data evaluating eltanexor in patients with higher-risk myelodysplastic syndrome (MDS).

"Efficacy data from our ongoing STOMP study investigating selinexor in combination with standard of care anti-myeloma agents continue to demonstrate a strong rationale for selinexor’s potential expanded role in the future multiple myeloma treatment paradigm," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "The Kyprolis arm of the STOMP study continues to show clear signs of clinical activity, including a complete response rate of 21%, in patients with heavily pretreated Kyprolis-naïve multiple myeloma. Additionally, preliminary data from the Revlimid arm of the Phase 1b/2 STOMP study show early but encouraging clinical activity, including in one patient who achieved a complete response, in patients with multiple myeloma in the front-line setting. And finally, we are pleased to be presenting new data from the eltanexor program showing impressive early activity, including a high rate of complete responses in elderly patients with higher-risk MDS."

Updated Data from Phase 1b/2 STOMP Study Evaluating Selinexor in Combination with Kyprolis and Low-dose Dexamethasone (SKd) in Patient with Relapsed or Refractory Multiple Myeloma

In this arm of the Phase 1b/2 STOMP study, oral selinexor (dosed once-weekly) is being evaluated in combination with Kyprolis (56mg/m2 or 70mg/m2 once weekly) and low dose dexamethasone (orally, 40mg once weekly or 20mg twice weekly) in patients with relapsed refractory multiple myeloma who have received at least two prior therapies, which can include previous treatment with a proteasome inhibitor, one or more immunomodulatory drugs (e.g., Revlimid or Pomalyst) or Darzalex. The median number of prior treatments was four (range: 2-8). The following table is a summary of the efficacy results:

Best Responses1 in Evaluable SKd Patients as of 1-Oct-20192
Category N ORR CR VGPR PR
All (Kyprolis-naïve) 14 10 (71%) 3 (21%) 7 (50%) -
Key: ORR=Overall Response Rate (CR+VGPR+PR); CR=Complete Response; VGPR=Very Good Partial Response; PR=Partial Response
1 Responses were adjudicated according to the International Myeloma Working Group criteria
2 Based on interim unaudited data

All patients had reductions in M-protein from baseline, with 71% of patients experiencing a reduction of ≥90%. Median progression-free survival (PFS) has not yet been reached.

Among the patients evaluated for safety as of the data cutoff date, the most common treatment-related adverse events (AEs) were cytopenias, along with gastrointestinal and constitutional symptoms; most were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (71%), fatigue (43%), anorexia (36%), vomiting (36%) and weight loss (36%), and were mostly Grade 1 and 2 events. As expected, the most common treatment-related Grade ≥3 AEs were hematologic AEs and included thrombocytopenia (64%), anemia (14%) and leukopenia (14%). The recommended Phase 2 dose (RP2D) was identified as selinexor 80mg and Kyprolis 56mg/m2 and enrollment continues using this regimen.

New Data from Phase 1b/2 STOMP Study Evaluating the All Oral Combination of Selinexor with Revlimid and Low-dose Dexamethasone (SRd) in Patients with Newly Diagnosed Multiple Myeloma

In this all oral arm of the Phase 1b/2 STOMP study in patients with newly diagnosed multiple myeloma, selinexor (60mg once-weekly) is being combined with Revlimid (25mg orally, once daily) and low dose dexamethasone (orally, 40mg once weekly or 20mg twice weekly). The following table is a summary of the efficacy results:

Best Responses1 in Evaluable SRd Patients as of 1-Oct-20192
Category N3 ORR CR VGPR4 PR
All 7 6 (86%) 1 (14%) 4 (57%) 1 (14%)
Key: ORR=Overall Response Rate (CR+VGPR+PR)
1 Responses were adjudicated according to the International Myeloma Working Group criteria
2 Based on interim unaudited data
3 One patient was not evaluable for response due to withdrawn consent prior to disease follow-up
4 One VGPR was confirmed on Oct 10, 2019 (after data cut); two VGPR are unconfirmed

The data are early and the median PFS was not reached. Among the patients evaluable for safety, the most common treatment-related AEs were cytopenias, along with gastrointestinal and constitutional symptoms; most were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were diarrhea (63%), weight loss (63%), nausea (50%), constipation (38%), fatigue (38%), hypokalemia (38%) and insomnia (38%) and were mostly Grade 1/2. The most common Grade ≥3 AEs were neutropenia (75%), anemia (50%) and thrombocytopenia (25%). Amongst the five patients evaluable for dose limiting toxicities (DLTs), there were no DLTs observed.

Comparison of Overall Survival Rates Between the Phase 2b STORM Study and the MAMMOTH Study

Another key presentation at ASH (Free ASH Whitepaper) 2019 highlights encore data comparing the overall survival (OS) rate from the retrospective MAMMOTH study (Leukemia, 2019). The MAMMOTH study evaluated outcomes of patients with relapsed or refractory multiple myeloma (RRMM) treated at major academic medical centers. This ASH (Free ASH Whitepaper) presentation highlighted results from a comparison of outcomes from patients with RRMM after their disease became refractory to CD38 monoclonal antibodies with a matched cohort of patients from Karyopharm’s Phase 2b STORM study, which served as the basis for the XPOVIO accelerated approval. Thus, patients in STORM who received selinexor and dexamethasone as first line of therapy after their disease became triple class refractory (n=64) were compared with matched patients receiving currently available therapies from the MAMMOTH cohort (n=128), showed an unadjusted hazard ratio (HR) for death of 0.64 (p=0.043), while an adjusted analysis, which takes into consideration differences in baseline characteristics between the two groups, showed a HR of 0.55 (p=0.009). The median OS of patients in STORM was 10.4 months and in MAMMOTH was 6.9 months. These results are consistent with previous presented results of STORM patients versus those from the Flatiron Health Analytics Database (FHAD) from patients with RRMM treated primarily in the community setting (Richardson, et al. ASCO (Free ASCO Whitepaper) 2019). In that analysis, the median OS of patients in STORM was 10.4 months and in FHAD was 5.8 months (p=0.036).

Updated Phase 1/2 Clinical Data for Oral Eltanexor in Elderly Patients with Higher-Risk MDS

This Phase 1/2 study is evaluating the safety, tolerability and anti-tumor activity of single-agent oral eltanexor (10mg or 20mg once-daily for 5 days per week) in elderly patients with higher-risk MDS. All patients were refractory to hypomethylating agents. The following table is a summary of the efficacy results:

Best Responses1 in Eltanexor Patients2
Category N ORR mCR SD
All patients 20 7 (35%) 7 (35%) 5 (25%)
Key: ORR=Overall Response Rate (mCR+HI [not observed]); mCR=Complete Response without marrow recovery; HI=Hematologic Improvement; SD=Stable Disease
1 Responses assessments were made by the treating physician according to the 2006 International Working Group (IWG) Response Criteria for MDS
2 Based on interim unaudited data

Median overall survival was 10.6 months. The most common treatment-related AEs were hematologic, gastrointestinal and constitutional. The most common non-hematologic treatment-related AEs were nausea (45%), decreased appetite (40%), fatigue (35%), diarrhea (35%) and dysgeusia (25%); the vast majority were Grade 1 or 2. The most common Grade ≥3 AEs were anemia (30%), neutropenia (25%), thrombocytopenia (20%) and leukopenia (15%). AEs were dose-dependent and managed with supportive care and dose modification. This Phase 1/2 study remains ongoing.

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Viracta Announces Positive Phase 1b/2 Data Presented at Oral Presentation on Lead Program for Epstein-Barr Virus (EBV)-associated Relapsed/Refractory Lymphomas at the 2019 American Society of Hematology (ASH) Annual Meeting

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Blueprint Medicines Announces Initial Data from Phase 2 PIONEER Trial of Avapritinib
in Patients with Indolent Systemic Mastocytosis Showing Activity at All Dose Levels Tested

BeiGene Announces Clinical Data on BRUKINSA™ (Zanubrutinib) at the 61st American Society of Hematology (ASH) Annual Meeting

Karyopharm Presents XPOVIO® (Selinexor) and Eltanexor Data at the American Society of Hematology 2019 Annual Meeting