On September 1, 2021 OncoQuest Pharmaceuticals Inc., ("OncoQuest") a clinical-stage biopharmaceutical company focused on the development and commercialization of immunotherapies for cancer, reported the first patient enrolled in each of two investigator initiated clinical trials assessing the safety and efficacy of oregovomab in a previously treated recurrent ovarian cancer setting (Press release, OncoQuest, SEP 1, 2021, View Source [SID1234587126]).

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The first study, led byProf. Jung KH, is being conducted at three centres in Korea (Korea Anam Hospital, Seoul St. Mary’s Hospital and Seoul Asan Hospital). This is a Phase 1b/2 clinical trial evaluation of the safety and efficacy of oregovomab when used in combination with bevacizumab, paclitaxel, and carboplatin in subjects with platinum sensitive recurrent ovarian cancer. Oregovomab has previously been established to augment the activity of carboplatin and paclitaxel through immune stimulation, and bevacizumab augments the activity of carboplatin and paclitaxel by inhibiting angiogenesis. The study will establish the safety and compatibility of the combination of these agents as possible approaches in patient management(ClinicalTrials.gov Identifier: NCT04938583). This study is supported by Korean Government’s K-Master program (KM-21) under the guidance of Prof. Kim YH at the Korea University Anam Hospital and Professor Park KH at Korea University College of Medicine.

The second study (ORION-02), led by Clinical Assistant Professor Jack Chan, is being conducted at a single centre in Singapore (National Cancer Centre Singapore). This is a Phase 1/2 clinical trial evaluation of the safety and efficacy of platinum-based chemotherapy, oregovomab and the PD-1 blockade agent, nivolumab, in subjects with platinum sensitive recurrent epithelial cancer of ovarian, tubal, or peritoneal origin (ClinicalTrials.gov Identifier: NCT04620954). The safety of oregovomab in combination with nivolumab has already been established in the ORION-01 study (ClinicalTrials.gov Identifier: NCT03100006).

OncoQuest has completed a Phase II study using oregovomab in combination with a TLR-3 agonist (Hiltonol) in the recurrent ovarian cancer setting (ClinicalTrials.gov Identifier: NCT03162562). Oregovomab is currently being tested in a global Phase III study in 12 countries in combination with carboplatin and paclitaxel chemotherapy in the front-line ovarian cancer setting (ClinicalTrials.gov Identifier: NCT04498117).

"We are committed to continue to work with investigators to explore the potential of oregovomab in combination therapies for treating ovarian cancer in both front line and recurrent settings. Progress in this area began in collaboration with Dr. Alan Gordon (Gynecologic Oncology2004 94:340-351) that identified potential favourable interactions between oregovomab and both carboplatin and doxorubicin in the recurrent disease setting. Those initial results led eventually to the observations recently reported by Brewer et al (Gynecologic Oncology 2020 156:523-529) that combining oregovomab with carboplatin and paclitaxel in a front-line setting improves outcomes", said Dr. Madiyalakan, Chairman of OncoQuest. OncoQuest is also in the process of initiating a clinical trial using oregovomab with niraparib in the recurrent ovarian cancer setting. "These additional clinical studies will guide us to select the optimal combinations for treatment throughout the course of this difficult disease," added Dr. Madiyalakan.

About Oregovomab.

Oregovomab is a murine IgG against CA 125. Indirect immunization with oregovomab interacts with immune modulating properties of infused paclitaxel and carboplatin resulting in synergistic clinical benefit as observed in this phase 2 trial. In a randomized Phase 2 clinical trial of 97 patients, treatment with Oregovomab demonstrated a highly clinically significant outcome for both progression-free and overall survival favoring the addition of oregovomab to a standard of care chemotherapy combination of carboplatin and paclitaxel. The risk of progression and of death was reduced by more than 50% when compared to placebo, and safety data showed that oregovomab did not add incremental toxicity to the chemotherapy regimen. Clinical and translational results were published in Gynecologic Oncology (2020 156:523-529) and Cancer Immunology and Immunotherapy (2020 69: 383-397), respectively.

On September 1, 2021 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, and GenFleet Therapeutics (Shanghai) Inc. ("GenFleet"), a clinical-stage biotechnology company developing cutting-edge therapies in oncology and immunology, reported that they have entered into an exclusive license agreement for the development and commercialization of GenFleet’s lead KRAS G12C candidate, GFH925 in China, including mainland China, Hong Kong, Macau and Taiwan with additional option-in rights for global development and commercialization (Press release, Innovent Biologics, SEP 1, 2021, View Source [SID1234587125]).

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GFH925, GenFleet’s lead KRAS G12C candidate, has recently received Investigational New Drug (IND) approval from National Medical Products Administration (NMPA) in China. Preclinical data showed that GFH925 has potential best-in-class activity that can effectively inhibit the growth of a variety of tumor cell lines carrying the KRAS G12C mutation, which may be helpful in accelerating the clinical validation of GFH925. In addition, other preclinical data have also demonstrated the potent potential for GFH925 in combination therapies.

According to the agreement, Innovent will be responsible for clinical development and commercialization of GFH925 in China, while retaining option-in right for development and commercialization outside of China as well. Following approval of a New Drug Application (NDA), Innovent will leverage its broad commercialization capability that includes an experienced commercialization team with extensive nationwide coverage to roll out GFH925, with the goal to benefit cancer patients in China. GenFleet will continue to be responsible for supplying GFH925 for both development and commercial purposes in China.

GenFleet will receive an upfront payment of US$22 million at signing. If Innovent exercises the option-in rights, GenFleet will receive up to US$50 million of global development support from Innovent. Upon achieving certain pre-specified milestones in development, registration, and annual sales performance of GFH925 globally, GenFleet is eligible to receive up to US$240 million in milestone payments in addition to tiered royalties based on annual net sales of GFH925 both in China and global markets.

Dr. Yongjun Liu, President of Innovent said, stated, "GenFleet has rich experience in research and development and has built up a proprietary pipeline of large and small molecule assets. We are delighted to form this strategic collaboration with GenFleet. Innovent is deeply engaged in the oncology area having built up a robust oncology pipeline of 20 clinical stage assets, an industry-leading medical operations and regulatory affairs team, a broad commercial channel and a professional commercial team of over 2000 people. KRAS G12C is an important mutation in multiple tumor types such lung cancer and solid tumors. Innovent has established a wide coverage on major tumor types including lung cancer. The collaboration on GFH925 will explore its potentials in clinical trials for both mono therapy and combination therapy such as combination with PD-1 which can further enhance our coverage in oncology area. By leveraging our synergy in clinical development and commercialization, we hope to expedite the development and launch of GFH925. Meanwhile, KRAS inhibitor has a promising global market potential. With the option-in rights for global development and commercialization, we look forward to bringing GFH925 as a new and more effective treatment option to patients both in China and globally.

Dr. Jiong Lan, CEO of GenFleet Therapeutics, stated, "We are pleased to announce our first major out-license collaboration with Innovent, an industry leading biopharmaceutical company which has demonstrated many successful track records of developing and commercializing novel anti-cancer therapies. RAS used to be an undruggable target and there was no KRAS G12C inhibitor moving into the clinics when GenFleet started the program, which highlights our "globally new" pipeline strategy that focuses on novel mechanisms of action. The partnership is not only a recognition of GFH925, a KRAS/G12C inhibitor with potential best-in-class differentiation, but also GenFleet’s internal discovery and development capability as well. The global scope of this collaboration will benefit not only patients in China, but also those throughout the world. In addition, we share the same vision of swiftly tackling unmet medical needs and the same culture of agile R&D in a biotech setting.

Professor Yilong Wu, Director of Guangdong Lung Cancer Institute, stated, "KRAS mutation is widespread among patients of non-small cell lung cancer, pancreatic cancer, colorectal cancer, etc. Preclinical data has shown that GFH925 is differentiated from other KRAS G12C inhibiting products, and we look forward to positive results of GFH925’s safety/tolerability and efficacy. Moreover, we will optimize our precision treatment plans and pave the way for the potential of combination therapies for patients with KRAS G12C gene mutation."

About GFH925 (KRAS G12C Inhibitor)

Being developed by GenFleet Therapeutics, GFH925 is a novel, orally active, potent KRAS G12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRAS G12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of GFH925 towards G12C. Subsequently, GFH925 effectively inhibits the downstream signal pathway to induce tumor cells’ apoptosis and cell cycle arrest.

On September 1, 2021 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage biotechnology company developing allogeneic CAR T and in vivo gene correction therapies with its ARCUS genome editing platform, and Tiziana Life Sciences plc (Nasdaq: TLSA / LSE: TILS), a clinical stage biotechnology company focused on innovative therapeutics for oncology, inflammation, and infectious diseases, reported an exclusive license agreement to explore Tiziana’s foralumab, a fully human anti-CD3 monoclonal antibody (mAb), as an agent to induce tolerance of allogeneic CAR T cells to potentially improve the clinical outcome of CAR T cell therapy (Press release, Precision Biologics, SEP 1, 2021, View Source [SID1234587124]).

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The Cluster of Differentiation (CD) 3 is a receptor on effector T cells and an anti-CD3 antibody, such as foralumab, has the potential to eliminate or tolerize patient effector T cells. Precision’s manufacturing process, which uses ARCUS to knock out the TRAC gene and implements a CD3-depletion step, produces allogeneic CAR T candidates that are >99.9% CD3-negative. Thus, an anti-CD3 antibody, such as foralumab, might be used to enable the CAR T cells to expand, proliferate, and persist to maximize long term clinical benefits.

Under the terms of the agreement, Precision gains an exclusive license to use foralumab as a lymphodepletion agent in conjunction with its allogeneic CAR T therapeutics for the treatment of cancers. Precision will be responsible for the development, commercialization, and costs for use of foralumab, and Tiziana will receive upfront payment, certain milestone payments, and royalties for foralumab.

"We are building out an allogeneic CAR T platform with editing strategies and novel conditioning regimens, such as a lymphodepleting agent like foralumab, for a broad range of hematologic malignancies and solid tumors," said Alan List, M.D., Chief Medical Officer at Precision BioSciences. "By combining Precision’s know-how in constructing novel CAR T products with novel conditioning regimens, we will explore this approach to potentially improve durability of clinical responses to our therapeutic platform."

"We’re pleased to offer Precision the exclusive opportunity to explore foralumab, our fully human anti-CD3 monoclonal antibody, for use as a potential lymphodepletion strategy with their allogeneic CAR T programs," said Kunwar Shailubhai, Chief Executive Officer and Chief Scientific Officer of Tiziana Life Sciences. "While CAR T therapies have been clinically successful, relapse rates remain high, which continues to limit broad utility. We are impressed with Precision’s novel approaches to CAR T development, offering the potential for a meaningful off-the-shelf solution. Further, given Precision’s approach to manufacturing that produces CAR T cells virtually CD3-negative, we believe use of foralumab as a lymphodepletion or tolerizing agent has the potential, either alone or in combination with other co-stimulatory molecules, to improve the long-term success of CAR T in cancer treatment."

About Precision’s Allogeneic CAR T Platform

Precision is advancing a pipeline of cell-phenotype optimized allogeneic CAR T therapies, leveraging fully scaled, proprietary manufacturing processes. The Company’s allogeneic CAR T platform is designed to maximize the number of patients who can potentially benefit from CAR T therapy. Precision carefully selects high-quality T cells derived from healthy donors as starting material, then uses its ARCUS genome editing technology to modify the cells via a single-step engineering process. By inserting the CAR gene at the T cell receptor (TCR) locus, this process knocks in the CAR while knocking out the TCR, which is designed to create a consistent product that can be reliably and rapidly manufactured and is designed to prevent graft-versus-host disease. Precision optimizes its CAR T therapy candidates for immune cell expansion in the body by maintaining a high proportion of naïve and central memory CAR T cells throughout the manufacturing process and in the final product.

About Foralumab

Foralumab (TZLS-401, formerly NI-0401), the only entirely human anti-CD3 mAb, shows reduced release of cytokines as compared to other anti-CD3 mAbs after IV administration in patients with Crohn’s disease with decreases in the classic side effects of cytokine release syndrome and improves the overall safety profile of Foralumab. In a humanized mouse model (NOD/SCID IL2γc-/-), it was shown that while targeting the T cell receptor, orally administered Foralumab modulates immune responses of the T cells, enhances regulatory T-cells (Tregs) and thus provides therapeutic benefit in treating inflammatory and autoimmune diseases without the occurrence of potential adverse events usually associated with parenteral mAb therapy (Ogura M. et al., 2017 Clin Immunol 183, 240-246). Based on animal studies, the nasal and oral administration of Foralumab offers the potential for the immunotherapy of autoimmune and inflammatory diseases in a safe manner by the induction of Tregs.

On September 1, 2021 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, reported that BRUKINSA (zanubrutinib) has received approval from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) (Press release, BeiGene, SEP 1, 2021, View Source [SID1234587123]).

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"The ASPEN trial provided compelling evidence that BRUKINSA is a highly active BTK inhibitor in Waldenström’s macroglobulinemia, and compared to the first-generation BTK inhibitor, showed improved tolerability across a number of clinically important side effects. The approval of BRUKINSA provides an important new option for targeted therapy in Waldenström’s macroglobulinemia"

"We are delighted by today’s FDA approval for BRUKINSA in its second indication, offering a new treatment option with demonstrated efficacy and safety benefits for patients with Waldenström’s macroglobulinemia. As shown in the ASPEN trial, BRUKINSA can improve treatment outcomes for these patients and potentially make a positive impact on their lives," commented Jane Huang, M.D., Chief Medical Officer, Hematology at BeiGene.

Dr. Huang continued, "With 11 regulatory approvals in under two years, including two in the U.S., BRUKINSA is demonstrating its growing utility as a treatment option for B-cell malignancies and expanding its footprint to potentially benefit more patients worldwide. We will continue to evaluate BRUKINSA in its broad global clinical program and look forward to additional clinical evidence to establish its position as a potentially best-in-class medicine."

"The ASPEN trial provided compelling evidence that BRUKINSA is a highly active BTK inhibitor in Waldenström’s macroglobulinemia, and compared to the first-generation BTK inhibitor, showed improved tolerability across a number of clinically important side effects. The approval of BRUKINSA provides an important new option for targeted therapy in Waldenström’s macroglobulinemia," said Steven Treon, M.D., Ph.D., Director of the Bing Center for Waldenström’s Macroglobulinemia Research at the Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School.

"The approval of BRUKINSA in Waldenström’s macroglobulinemia, which is the second therapy approved specifically for the treatment of this rare type of lymphoma, is positive news for patients. Expanded treatment options offer new hope for those living with this disease and can potentially improve patient experience, especially oral therapies that can be given as a single agent," said Pete DeNardis, Chair of the Board at the International Waldenström’s Macroglobulinemia Foundation (IWMF).

The FDA’s approval of BRUKINSA in WM is primarily based on efficacy results from the multicenter, open-label Phase 3 ASPEN trial (NCT03053440) comparing BRUKINSA to ibrutinib in patients with WM. A total of 201 patients with a MYD88 mutation (MYD88MUT) were enrolled in the randomized Cohort 1.

The primary efficacy endpoint of the ASPEN trial was very good partial response (VGPR) rate in the overall intention-to-treat (ITT) population as assessed by independent review committee (IRC). Based on the modified Sixth International Workshop on Waldenström’s Macroglobulinemia (IWWM-6) response criteria (Treon 2015), the VGPR rate was 28% with BRUKINSA, compared to 19% with ibrutinib; based on the IWWM-6 response criteria (Owen et al 2013), the VGPR rate was 16% with BRUKINSA, compared to 7% with ibrutinib.

In the FDA-approved label, the major efficacy outcome is defined as response rate of partial response (PR) or better as assessed by IRC. Based on either IWWM-6 response criteria, the response rate was 78% with BRUKINSA (95% CI: 68, 85), compared to 78% with ibrutinib (95% CI: 68, 86), and the event-free duration of response (DoR) at 12 months was 94% with BRUKINSA (95% CI: 86, 98), compared to 88% with ibrutinib (95% CI: 77, 94).

The most common (≥20%) adverse reactions based on the pooled safety population of 779 patients were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, rash, hemorrhage, musculoskeletal pain, decreased hemoglobin, bruising, diarrhea, pneumonia, and cough.

The recommended dose of BRUKINSA is either 160 mg twice daily or 320 mg once daily, taken orally with or without food. The dose may be adjusted for adverse reactions and reduced for patients with severe hepatic impairment and certain drug interactions.

About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA is approved in the following indications and regions:

For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (United States, November 2019)*;
For the treatment of MCL in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of relapsed or refractory MCL (United Arab Emirates, February 2021);
For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (Canada, March 2021);
Registered and reimbursed for the treatment of MCL in patients who have received at least one prior therapy (Israel, April 2021);
For the treatment of adult patients with WM who have received at least one prior therapy (China, June 2021)**;
For the treatment of MCL in adult patients who have received at least one prior therapy (Canada, July 2021);
For the treatment of adult patients with MCL who have received at least one previous therapy (Brazil, August 2021); and
For the treatment of adult patients with WM (United States, August 2021).
To-date, more than 30 marketing authorization applications in multiple indications have been submitted in the United States, China, the European Union, and more than 20 other countries or regions.

* This indication was 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.

** This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

IMPORTANT U.S. 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 hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.0% of patients treated with BRUKINSA monotherapy. Hemorrhage events of any grade occurred in 35% 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 28% 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 (28%), thrombocytopenia (11%) and anemia (7%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 13% of patients, and Grade 4 thrombocytopenia occurred in 4% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 13% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 7% of patients. Other second primary malignancies included malignant solid tumors (4%), melanoma (1.4%), and hematologic malignancies (1.2%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter have occurred in 2.8% 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 0.8% 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 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 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 including laboratory abnormalities in ≥20% of patients who received BRUKINSA (N = 779) were decreased neutrophil count (56%), upper respiratory tract infection (49%), decreased platelet count (44%), rash (35%), hemorrhage (35%), musculoskeletal pain (30%), decreased hemoglobin (28%), bruising (25%), diarrhea (23%), pneumonia (22%), and cough (21%).

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.

On September 1, 2021 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported that the Phase 3 PANTHER (Pevonedistat-3001) study did not achieve pre-defined statistical significance for the primary endpoint of event-free survival (EFS) (Press release, Takeda, SEP 1, 2021, View Source [SID1234587122]). The trial evaluated whether the combination of pevonedistat plus azacitidine as first-line treatment for patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and low-blast acute myeloid leukemia (AML) improved EFS versus azacitidine alone. An event in the trial is defined as death or transformation to AML in participants with higher-risk MDS or CMML, whichever occurs first, and death in participants with AML.

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"While we are disappointed with this outcome, we are continuing to gain a greater understanding of the full data set and hope that findings from this Phase 3 study will provide information to help guide research and development for potential treatment options for these underserved patient populations," said Chris Arendt, PhD, Head, Oncology Cell Therapy and Therapeutic Area Unit, Takeda. "We would like to thank the patients, families, advocacy organizations and investigators that participated in this trial, without whom this meaningful research would not have been possible. Takeda remains committed to conducting important research and transforming the lives of patients with cancer."

Full data results will be submitted for presentation at an upcoming medical congress. Investigators have been informed of the outcome so they can discuss the potential impact with study participants. Takeda will work with investigators who will determine the most appropriate action for each individual patient enrolled in the study.

About Pevonedistat
Pevonedistat is a NEDD8-activating enzyme (NAE) inhibitor that leads to cancer cell death by disrupting protein homeostasis. The Phase 3 PANTHER study (Pevonedistat-3001) did not achieve pre-defined statistical significance for the primary endpoint of event-free survival (EFS) and the data results are currently being evaluated. The safety profile was consistent with previously reported data for this combination. Pevonedistat is an investigational drug for which safety and efficacy have not been established.

Takeda’s Commitment to Oncology
Our core R&D mission is to deliver novel medicines to patients with cancer worldwide through our commitment to science, breakthrough innovation and passion for improving the lives of patients. Whether it’s with our hematology therapies, our robust pipeline, or solid tumor medicines, we aim to stay both innovative and competitive to bring patients the treatments they need. For more information, visit www.takedaoncology.com.