Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial Of Quizartinib Administered in Combination With Induction and Consolidation Chemotherapy and Administered as Maintenance Therapy in Adult Patients With Newly Diagnosed FLT3-ITD Negative Acute Myeloid Leukemia

This study will compare the effects of Quizartinib versus placebo in combination with chemotherapy in participants with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) negative acute myeloid leukemia (AML).

开始日期2024-11-19

申办/合作机构

Daiichi Sankyo Co., Ltd.

NCT06740825 / Completed临床1期

A Phase 1, Open Label, Randomized, Parallel Drug Interaction Study to Evaluate the Effect of a CYP3A Weak Inducer Rufinamide on the Pharmacokinetics of Quizartinib in Healthy Subjects

This study will evaluate the effect of CYP3A weak inducer rufinamide on the pharmacokinetics (PK) of Quizartinib in healthy subjects

开始日期2024-10-29

申办/合作机构

Daiichi Sankyo Co., Ltd.

NCT06740799 / Recruiting临床1期

A Phase 1, Multicenter, Open-Label, Single-Dose Study to Assess the Pharmacokinetics, Safety and Tolerability of Quizartinib in Subjects With Severe Impaired Hepatic Function

This study will evaluate and compare the PK in subjects with severe HI to that of matched healthy control subjects with normal hepatic function.

开始日期2024-09-30

申办/合作机构

Daiichi Sankyo Co., Ltd.

100 项与奎扎替尼相关的临床结果

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100 项与奎扎替尼相关的转化医学

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100 项与奎扎替尼相关的专利（医药）

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337

项与奎扎替尼相关的文献（医药）

2025-01-01·American Journal of Clinical Oncology

Maintenance Therapy in Acute Myeloid Leukemia

Review

作者: Sabakhtarishvili, Giorgi ; Ansari, Amir ; Tabbara, Imad A.

Acute myeloid leukemia (AML) poses significant challenges due to its high relapse rates despite initial successful induction chemotherapy. Maintenance therapy aims to prevent disease recurrence, particularly in high-risk patients. This review explores current maintenance treatments, their impacts on patient outcomes, and ongoing studies shaping the treatment landscape for AML. Hypomethylating agents like azacitidine and decitabine have shown promise in improving relapse-free and overall survival, particularly in older patients with AML ineligible for transplantation. Combination regimens involving azacitidine and venetoclax have demonstrated encouraging outcomes post–hematopoietic stem cell transplantation. Targeted therapies, particularly FLT3 inhibitors like midostaurin and quizartinib, have shown significant benefits in improving survival outcomes, especially in FLT3-mutated AML cases. Gilteritinib and sorafenib also exhibit the potential to reduce relapse rates post-transplant. Isocitrate dehydrogenase inhibitors, including ivosidenib and enasidenib, present novel options for postchemotherapy and posttransplantation maintenance. Immunotherapies, such as Wilms tumor 1 peptide-based vaccines and checkpoint inhibitors, are being explored, although results vary. Despite ongoing research, the role of maintenance chemotherapy remains uncertain, with inconsistent outcomes across trials. The approval of oral azacitidine represents a significant advancement, emphasizing the need for further investigation into personalized maintenance approaches. In conclusion, the evolving landscape of maintenance therapy and integrating targeted therapies in AML offers promising avenues for improving patient outcomes.

2024-12-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Identification of furo[2,3-d]pyrimidin-4-ylsulfanyl-1,3,4-thiadiazole derivatives as novel FLT3-ITD inhibitors

Article

作者: Firoozpour, Loghman ; Kryštof, Vladimír ; Sadat-Ebrahimi, Seyed Esmaeil ; Peřina, Miroslav ; Emamgholipour, Zahra ; Mousavi, Alireza ; Jorda, Radek ; Řezníčková, Eva ; Peytam, Fariba ; Moradi, Mahfam ; Vojáčková, Veronika ; Foroumadi, Alireza ; Grúz, Jiří

Given the significant prevalence of FLT3 receptor and its mutations in acute myeloid leukemia (AML) pathogenesis, we present a novel series of furo[2,3-d]pyrimidin-1,3,4-thiadiazole-urea derivatives, designed to exhibit FLT3-ITD inhibitory activity. These compounds demonstrated cytotoxicity in FLT3-ITD expressing AML cell lines MOLM-13 and MV4-11 in the nanomolar range, with significant selectivity over the K562 cell line. In-depth evaluations of example compound 49 revealed its efficacy in suppressing FLT3 phosphorylation and the downstream signaling molecules, including STAT5 and ERK1/2. Notably, compound 49 demonstrated cytotoxic effects in Ba/F3 cells expressing FLT3-ITD or FLT3-ITD-F691L mutant, exceeding the potency of both sorafenib and quizartinib. Molecular docking studies suggest that this compound binds to the active site of FLT3 in a type II manner. The study suggests that substituted furo[2,3-d]pyrimidines could be useful additions to the growing field of FLT3-targeted therapy for AML. These compounds have the potential to serve as novel FLT3-ITD inhibitors and may offer insights for developing future therapeutic strategies in AML.

2024-12-01·CTS-Clinical and Translational Science

Population pharmacokinetic analysis of quizartinib in patients with newly diagnosed FLT3‐internal‐tandem‐duplication‐positive acute myeloid leukemia

Article

作者: Abutarif, Malaz ; Kurumaddali, Abhinav ; Vaddady, Pavan ; Glatard, Anaïs ; Inoue, Hiroyuki ; Smania, Giovanni ; Zheng, Ming ; Nakayama, Shintaro

Abstract:

The population pharmacokinetics (PK) of quizartinib and its pharmacologically active metabolite AC886 have been previously described in healthy volunteers (HV) and relapsed/refractory (R/R) FLT3‐internal‐tandem‐duplication‐positive (FLT3‐IDT‐positive) acute myeloid leukemia (AML) patients receiving quizartinib monotherapy. In this analysis, we characterized the population PK of quizartinib and AC886 in newly diagnosed FLT3‐ITD‐positive AML patients receiving standard induction and consolidation chemotherapy as background treatment, using data from the Phase 3 QuANTUM‐First trial and 12 earlier studies. Quizartinib PK were best described by a three‐compartment model with sequential zero‐ and first‐order absorption and first‐order elimination. A two‐compartment model with first‐order metabolite formation and first‐order elimination best fitted AC886 data. The PK of both moieties showed large interindividual variability (approximately 70% coefficient of variation for systemic clearances). The use of strong cytochrome P450 3A (CYP3A) inhibitors had the largest impact on exposure, increasing the steady‐state area under the curve during the dosing interval (AUCss) by 1.8‐fold. This is consistent with observations in HV and R/R AML patients and confirms the need for dose adjustments during coadministration. A novel finding in newly diagnosed AML patients was the phase‐dependent change in steady‐state quizartinib exposure: dose‐normalized AUCss values were 0.6‐fold during induction, similar during consolidation, and 1.4‐fold during continuation compared to R/R AML patients receiving quizartinib monotherapy. The present analysis highlighted the comparison of quizartinib and AC886 PK between newly diagnosed AML patients and previously studied populations, informed dose modifications needed with strong CYP3A inhibitors, and supported the use of derived individual exposure metrics in separate exposure‐response analyses.

项与奎扎替尼相关的新闻（医药）

2024-12-10

·Business Wire

QuANTUM-Wild Phase 3 Trial of VANFLYTA® Initiated in Patients with Newly Diagnosed FLT3-ITD Negative AML

TOKYO & BASKING RIDGE, N.J.--( BUSINESS WIRE )--The first patient has been dosed in the QuANTUM-Wild phase 3 trial evaluating Daiichi Sankyo’s (TSE: 4568) VANFLYTA ® (quizartinib) in combination with standard intensive induction and consolidation chemotherapy followed by single-agent maintenance in adults with newly diagnosed FLT3 -ITD negative acute myeloid leukemia (AML). AML is an aggressive blood cancer with a five-year overall survival rate of approximately 32%. 1, 2 Targeted therapy with FLT3 inhibitors has improved survival for some patients with FLT3 gene mutations, which most commonly occur as FLT3 -ITD. 3 However, about 90% of patients with AML overexpress FLT3 regardless of mutational status. 1, 4, 5 No FLT3 inhibitors are currently approved for patients without FLT3 mutations. “Preliminary data have shown promising results for VANFLYTA in patients with FLT3 -ITD negative acute myeloid leukemia, which includes patients without FLT3 mutations and patients with TKD mutations,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “We have initiated the QuANTUM-Wild trial to further confirm the potential role of VANFLYTA combined with standard chemotherapy and as subsequent maintenance monotherapy in this broader population of patients with AML who are in need of new treatment options to potentially reduce the risk of relapse and improve overall survival.” The QuANTUM-Wild trial was initiated based on results of the QUIWI phase 2 trial evaluating VANFLYTA in combination with standard intensive chemotherapy and as subsequent maintenance monotherapy in adult patients with newly diagnosed FLT3 -ITD negative AML. The final results of QUIWI were presented at the 2024 American Society of Hematology Annual Meeting. 6 About the QuANTUM-Wild Trial QuANTUM-Wild is a randomized, double-blind, placebo-controlled global phase 3 trial evaluating the efficacy and safety of VANFLYTA in combination with standard intensive induction and consolidation therapy, including allogenic hematopoietic stem cell transplant (HSCT), followed by maintenance monotherapy, in adult patients aged 18 to 70 with newly diagnosed FLT3 -ITD negative AML. Patients will be randomized 2:2:1 into three treatment arms. In Arms A and B, patients will receive VANFLYTA or placebo, respectively, in combination with cytarabine and anthracycline induction and cytarabine consolidation chemotherapy, followed by up to three years of single-agent maintenance therapy. The primary endpoint for Arms A and B is overall survival. Secondary endpoints include event-free survival, duration of complete response, relapse-free survival, complete remission rate (CR), CR with minimal or measurable residual disease negativity, pharmacokinetic assessments and safety measures including treatment emergent adverse events. For purposes of exploratory analyses in the maintenance setting, patients in a third study arm (Arm C), will receive VANFLYTA in combination with intensive induction and consolidation chemotherapy followed by placebo maintenance monotherapy. QuANTUM-Wild is expected to enroll approximately 700 patients across Asia, Australia, Europe, North America and South America. For more information, please visit ClinicalTrials.gov . About Acute Myeloid Leukemia One of the most common forms of leukemia in adults, AML is an aggressive blood cancer with a five-year overall survival rate of approximately 32%. 1, 2, 3 Approximately 144,000 new cases of AML were diagnosed globally with more than 130,000 deaths reported in 2021. 7 Targeted therapy with FLT3 inhibitors has improved survival for some patients with FLT3 gene mutations, which most commonly occur as FLT3 -ITD. 3 However, about 90% of all patients with AML overexpress FLT3 regardless of activating mutations. 1, 4, 5 No FLT3 inhibitors are currently approved for patients without FLT3 mutations. FLT3 is a receptor tyrosine kinase protein that plays an important role in blood cell development but, when constitutively activated, FLT3 can contribute to AML development and growth. 8 About VANFLYTA VANFLYTA is an oral, highly potent and selective type II FLT3 inhibitor approved in more than 30 countries in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and as maintenance monotherapy following consolidation, for the treatment of adult patients with newly diagnosed AML that is FLT3 -ITD positive based on the results from the QuANTUM-First trial. In the U.S., VANFLYTA is not indicated as maintenance monotherapy following allogeneic HSCT; improvement in overall survival with VANFLYTA in this setting has not been demonstrated. VANFLYTA also is approved in Japan for the treatment of patients with relapsed/refractory AML that is FLT3 -ITD mutation positive, as detected by an approved test, based on results from the QuANTUM-R trial. About the VANFLYTA Clinical Development Program The VANFLYTA clinical development program includes the QuANTUM-Wild phase 3 trial in adult patients with newly diagnosed FLT3 -ITD negative AML, a phase 1/2 trial in pediatric and young adult patients with relapsed/refractory FLT3 -ITD positive AML in Europe, Asia and North America and several phase 1/2 combination studies as part of a strategic collaboration with The University of Texas MD Anderson Cancer Center. VANFLYTA U.S. Important Safety Information WARNING: QT PROLONGATION, TORSADES DE POINTES, and CARDIAC ARREST VANFLYTA ® (quizartinib) prolongs the QT interval in a dose- and concentration-related manner. Prior to VANFLYTA administration and periodically, monitor for hypokalemia or hypomagnesemia, and correct deficiencies. Perform electrocardiograms (ECGs) to monitor the QTc at baseline, weekly during induction and consolidation therapy, weekly for at least the first month of maintenance, and periodically thereafter. Torsades de pointes and cardiac arrest have occurred in patients receiving VANFLYTA. Do not administer VANFLYTA to patients with severe hypokalemia, severe hypomagnesemia, or long QT syndrome. Do not initiate treatment with VANFLYTA or escalate the VANFLYTA dose if the QT interval corrected by Fridericia’s formula (QTcF) is greater than 450 ms. Monitor ECGs more frequently if concomitant use of drugs known to prolong the QT interval is required. Reduce the VANFLYTA dose when used concomitantly with strong CYP3A inhibitors, as they may increase quizartinib exposure. Because of the risk of QT prolongation, VANFLYTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the VANFLYTA REMS. Indication VANFLYTA is indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)–positive as detected by an FDA-approved test. Limitations of Use VANFLYTA is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with VANFLYTA in this setting has not been demonstrated. Contraindications VANFLYTA is contraindicated in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes. Warnings and Precautions QT Prolongation, Torsades de Pointes, and Cardiac Arrest (See BOXED WARNING) VANFLYTA prolongs the QT interval in a dose- and concentration-dependent manner. The mechanism of QTc interval prolongation is via inhibition of the slow delayed rectifier potassium current, I Ks , as compared to all other medications that prolong the QTc interval, which is via the rapid delayed rectifier potassium current, I Kr . Therefore, the level of QTc prolongation with VANFLYTA that predicts the risk of cardiac arrhythmias is unclear. Inhibition of I Ks and I Kr may leave patients with limited reserve, leading to a higher risk of QT prolongation and serious cardiac arrhythmias, including fatal outcomes. Torsades de pointes, ventricular fibrillation, cardiac arrest, and sudden death have occurred in patients treated with VANFLYTA. Of the 1,081 patients with AML treated with VANFLYTA in clinical trials, torsades de pointes occurred in approximately 0.2% of patients, cardiac arrest occurred in 0.6% of patients, including 0.4% with a fatal outcome, and 0.1% of patients experienced ventricular fibrillation. These severe cardiac arrhythmias occurred predominantly during the induction phase. Of the 265 patients with newly diagnosed FLT3-ITD–positive AML treated with VANFLYTA in combination with chemotherapy in the clinical trial, 2.3% were found to have a QTcF greater than 500 ms and 10% of patients had an increase from baseline QTcF greater than 60 ms. The clinical trial excluded patients with a QTcF ≥450 ms or other factors that increased the risk of QT prolongation or arrhythmic events (eg, NYHA Class III or IV congestive heart failure, hypokalemia, family history of long QT interval syndrome). Therefore, avoid use in patients who are at significant risk of developing torsades de pointes, including uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, tachyarrhythmias, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism. Do not initiate treatment with VANFLYTA if the QTcF interval is greater than 450 ms. Do not use VANFLYTA in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes. Perform an ECG and correct electrolyte abnormalities prior to initiation of treatment with VANFLYTA. During induction and consolidation, perform an ECG prior to initiation and then once weekly during VANFLYTA treatment or more frequently as clinically indicated. During maintenance, perform ECGs prior to initiation, once weekly for at least the first month following dose initiation and escalation, and as clinically indicated thereafter. Do not escalate the dose if QTcF is greater than 450 ms. Perform ECG monitoring of the QT interval more frequently in patients who are at significant risk of developing QT interval prolongation and torsades de pointes, or following dose escalation. Monitor and correct hypokalemia and hypomagnesemia prior to and during treatment with VANFLYTA. Maintain electrolytes in the normal range. Monitor electrolytes and ECGs more frequently in patients who experience diarrhea or vomiting. Monitor patients more frequently with ECGs if coadministration of VANFLYTA with drugs known to prolong the QT interval is required. Reduce the VANFLYTA dose when used concomitantly with strong CYP3A inhibitors, as they may increase quizartinib exposure. Reduce VANFLYTA if QTc increases to greater than 480 ms and less than 500 ms. Interrupt and reduce VANFLYTA if QTc increases to greater than 500 ms. Permanently discontinue VANFLYTA in patients who develop recurrent QTc greater than 500 ms or QTc interval prolongation with signs or symptoms of life-threatening arrhythmia. VANFLYTA is available only through a restricted program under a REMS. VANFLYTA REMS VANFLYTA is available only through a restricted distribution program under a REMS called the VANFLYTA REMS because of the serious risk of QT prolongation, torsades de pointes, and cardiac arrest. Notable requirements of the VANFLYTA REMS include the following: Prescribers must be certified in the VANFLYTA REMS by enrolling and completing training. Prescribers must counsel patients receiving VANFLYTA about the risk of QT prolongation, torsades de pointes, and cardiac arrest, and provide patients with a Patient Wallet Card. Pharmacies that dispense VANFLYTA must be certified with the VANFLYTA REMS and must verify prescribers are certified through the VANFLYTA REMS. Further information about the VANFLYTA REMS is available at www.VANFLYTAREMS.com or by telephone at 1-855-212-6670. Embryo-Fetal Toxicity Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with VANFLYTA and for 7 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with VANFLYTA and for 4 months after the last dose. Adverse Reactions The safety of VANFLYTA (35.4 mg orally once daily with chemotherapy, 26.5 mg to 53 mg orally once daily as maintenance) in adult patients with newly diagnosed FLT3-ITD positive AML is based on QuANTUM-First. Serious adverse reactions in ≥5% of patients who received VANFLYTA plus chemotherapy were: febrile neutropenia (11%). Fatal adverse reactions occurred in 10% of patients who received VANFLYTA plus chemotherapy, including sepsis (5%), fungal infections (0.8%), brain edema (0.8%), and one case each of febrile neutropenia, pneumonia, cerebral infarction, acute respiratory distress syndrome, pulmonary embolism, ventricular dysfunction, and cardiac arrest. Permanent discontinuation due to an adverse reaction in patients in the VANFLYTA plus chemotherapy arm occurred in 20% of patients. The most frequent (≥2%) adverse reaction which resulted in permanent discontinuation in the VANFLYTA arm was sepsis (5%). Dosage interruptions of VANFLYTA due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dosage interruption in ≥2% of patients in the VANFLYTA arm included neutropenia (11%), thrombocytopenia (5%), and myelosuppression (3%). Dose reductions of VANFLYTA due to an adverse reaction occurred in 19% of patients. Adverse reactions which required dosage reductions in ≥2% of patients in the VANFLYTA arm were neutropenia (9%), thrombocytopenia (5%), and electrocardiogram QT prolonged (4%). The most common adverse reactions (≥10% with a difference between arms of ≥2% compared to placebo), including laboratory abnormalities, were decreased lymphocytes, decreased potassium, decreased albumin, decreased phosphorus, increased alkaline phosphatase, decreased magnesium, febrile neutropenia, diarrhea, mucositis, nausea, decreased calcium, abdominal pain, sepsis, neutropenia, headache, increased creatine phosphokinase, vomiting, upper respiratory tract infections, hypertransaminasemia, thrombocytopenia, decreased appetite, fungal infections, epistaxis, increased potassium, herpesvirus infections, insomnia, QT prolongation, increased magnesium, increased sodium, dyspepsia, anemia, and eye irritation. Drug Interactions Strong CYP3A Inhibitors VANFLYTA is a CYP3A substrate. Concomitant use of VANFLYTA with a strong CYP3A inhibitor increases quizartinib systemic exposure, which may increase the risk of VANFLYTA adverse reactions. Reduce the dosage of VANFLYTA. Strong or Moderate CYP3A Inducers Concomitant use of VANFLYTA with strong or moderate CYP3A inducers decreases quizartinib systemic exposure, which may reduce VANFLYTA efficacy. Avoid concomitant use of VANFLYTA with strong or moderate CYP3A inducers. QT Interval–Prolonging Drugs VANFLYTA prolongs the QT/QTc interval. Coadministration of VANFLYTA with other drugs that prolong the QT interval may further increase the incidence of QT prolongation. Monitor patients more frequently with ECG if coadministration of VANFLYTA with drugs known to prolong the QT interval is required. Use in Specific Populations Pregnancy VANFLYTA can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Lactation Advise women not to breastfeed during treatment with VANFLYTA and for one month after the last dose. Females and Males of Reproductive Potential Pregnancy Testing Verify pregnancy status in females of reproductive potential within 7 days before starting treatment with VANFLYTA. Contraception Females Advise female patients of reproductive potential to use effective contraception during treatment with VANFLYTA and for 7 months after the last dose. Males Advise male patients with female partners of reproductive potential to use effective contraception during treatment with VANFLYTA and for 4 months after the last dose. Infertility Females Based on findings from animal studies, VANFLYTA may impair female fertility. These effects on fertility were reversible. Males Based on findings from animal studies, VANFLYTA may impair male fertility. These effects on fertility were reversible. Pediatric Use Safety and effectiveness of VANFLYTA have not been established in pediatric patients. Geriatric Use No overall differences in safety or efficacy were observed between patients 65 years of age and older and younger adult patients. Renal Impairment No dosage adjustment is recommended in patients with mild to moderate renal impairment (CLcr 30 to 89 mL/min). VANFLYTA has not been studied in patients with severe renal impairment (CLcr <30 mL/min). Hepatic Impairment No dosage adjustment is recommended in patients with mild hepatic impairment or moderate hepatic impairment. VANFLYTA has not been studied in patients with severe hepatic impairment. To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc, at 1-877-437-7763 or the FDA at 1-800-FDA-1088 or fda.gov/medwatch . Please see Full Prescribing Information , including Boxed WARNINGS, and Medication Guide . About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com . References 1 Kennedy VE, et al. Front Oncol . 2020;10:612880. 2 National Cancer Institute SEER Program. Cancer Stat Facts: Leukemia - Acute Myeloid Leukemia . 3 Loschi M, et al. Int J Mol Sci . 2021;22(11):5873. 4 Li Y, et al. Blood . 2004;104(4):1137-44. 5 Gilliand G and Griffin J. Blood. 1 September 2002;100:5 6 Montesinos P, et al. Abstract #1512 . ASH 2024 Annual Meeting. 7 Zhou Y, et al . Biomark Res . 2024;12(1):101. 8 Daver N, et al. Leukemia . 2019;33(2):299–312.

临床结果临床3期上市批准ASH会议临床2期

2024-12-03

·第一三共中国

第一三共亮相ESMO亚洲、SABCS和ASH大会，展示肿瘤产品组合在实体瘤和血液瘤治疗方面的最新进展

● 三份最新报告展示三种DXd ADC在肺癌和乳腺癌领域的研究成果 ● “科技日”介绍第一三共研发管线数据和策略　　新泽西州巴斯金里奇-（2024年12月3日）- 第一三共将在其科技日之前的2024年欧洲肿瘤内科学会（ESMO）亚洲大会（#ESMOAsia24）、圣安东尼奥乳腺癌研讨会（#SABCS24）和美国血液学学会（#ASH24）年会上，报告其肿瘤产品组合用于治疗多种实体瘤和血液瘤的最新研究成果，涉及超过45篇摘要。　　ESMO亚洲大会、SABCS和ASH大会报告将展现第一三共在重塑肿瘤治疗新标准方面取得的进展。会议亮点包括ESMO Asia中的三项最新报告，包括datopotamab deruxtecan（Dato-DXd）治疗表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌（NSCLC）的2期研究TROPION-Lung05和3期研究TROPION-Lung01的汇总分析，以及SABCS报告的注射用德曲妥珠单抗（商品名：优赫得®，以下简称“T-DXd”）3期研究DESTINY-Breast06的亚组分析，治疗不可切除或转移性 HR阳性、HER2低表达（IHC 1+或 IHC 2+/ISH-）或HER2超低表达（IHC 0 伴膜染色）乳腺癌患者，以及patritumab deruxtecan（HER3-DXd）治疗早期HR阳性、HER2阴性乳腺癌患者的2期研究VALENTINE的初步结果。 Ken Takeshita 博士第一三共全球研发负责人　　在这些即将召开的会议，第一三共将重点介绍在难治性癌症方面的重要进展，包括肺癌、乳腺癌、胃癌、胆道癌以及急性髓系白血病（AML）和外周T细胞淋巴瘤。我们将持续推动获批药物和管线药物的重要研究进展，实现重塑癌症治疗新标准这一目标。肺癌、乳腺癌、胃癌和胆道癌领域创新成果亮相 ESMO 亚洲大会　　ESMO亚洲大会上展示的最新数据将重点介绍Dato-DXd用于既往经治EGFR突变晚期NSCLC患者的一项汇总分析结果，涵盖2期研究TROPION-Lung05以及3期研究TROPION-Lung01。　　两个小型口头报告包括Dato-DXd治疗既往经治HR阳性、HER2低表达或阴性乳腺癌的3期研究TROPION-Breast01中国患者的结果，以及T-DXd治疗既往经治HER2阳性晚期胃或胃食管结合部（GEJ）腺癌中国患者的2期研究DESTINY-Gastric06的最终结果。基于DESTINY-Gastric06的结果，T-DXd近期在中国获得附条件批准，即 T-DXd单药治疗既往接受过两种或两种以上治疗方案的局部晚期或转移性HER2阳性成人胃或胃食管结合部腺癌患者。　　还将海报展示三项进行中T-DXd临床试验的研究设计，包括3期研究DESTINY-BTC01，该研究将在既往未接受过治疗的HER2表达、局部晚期或转移性胆道癌患者中评价T-DXd联合PD-1/TIGIT双特异性抗体rilvegostomig和标准治疗的疗效；1b/2期研究DESTINY-Gastric03，该研究新增队列以在HER2阳性或HER2低表达胃或胃食管结合部（GEJ）腺癌患者中评价T-DXd联合rilvegostomig和化疗的效果。T-DXd 2期研究DESTINY-PanTumor02的第2部分也将在会议上展示，该部分入组既往经治的HER2表达转移性实体瘤患者并分为五个队列：肿瘤表达HER2 IHC 3+的患者（不包括乳腺癌、胃癌和结直肠癌）；肿瘤表达HER2 IHC 2+/ISH+的患者（不包括乳腺癌、胃癌和结直肠癌）；HER2 IHC 2+/1+子宫内膜癌患者；HER2 IHC2+/1+卵巢癌患者；以及HER2 IHC 2+/1+宫颈癌患者。　　　SABCS大会展示乳腺癌领域进展　　　　　SABCS 将介绍乳腺癌领域的最新成果，包括两个口头报告：3 期研究 DESTINY-Breast06的亚组分析结果，即既往内分泌治疗对以下患者治疗结局的影响：接受T-DXd对比化疗的既往接受至少一线内分泌治疗失败的不可切除或转移性HR阳性、HER2低表达（IHC 1+或 IHC 2+/ISH-）或HER2超低表达（IHC 0 伴膜染色）乳腺癌患者，以及2期研究VALENTINE的主要结果，该研究在高风险HR阳性、HER2阴性早期乳腺癌患者中评价新辅助HER3-DXd单药或与来曲唑联合治疗。　　会上报告的其他数据包括两份重点海报展示，突出介绍了3期研究DESTINY-Breast03的首次探索性生物标志物分析，该分析评估基因组改变对T-DXd与trastuzumab emtansine（T-DM1）相比治疗HER2阳性转移性乳腺癌患者疗效的影响，以及3b/4期研究DESTINY-Breast12中T-DXd对健康相关生活质量和神经功能的影响，该研究在既往经治HER2阳性、伴或不伴脑转移的转移性乳腺癌患者中进行。将以海报展示的形式报告1b期研究DESTINY-Breast08剂量扩展部分的最终结果，该研究在HER2低表达转移性乳腺癌患者中评价T-DXd与卡培他滨或capivasertib联合治疗。　　进行中研究的海报将展示DXd ADC与valemetostat联合治疗的phase 1b master protocol trial中子方案A的研究设计，该子方案研究评价T-DXd与EZH1和EZH2双重抑制剂valemetostat联合治疗用于既往经治HER2低表达不可切除或转移性乳腺癌患者，以及一项T-DXd与valemetostat联合治疗的phase 1b trial的研究设计，该研究在既往经治HER2低表达、HER2超低表达或HER2无表达转移性乳腺癌患者中评价联合给药的表现。血液肿瘤产品治疗白血病和淋巴瘤的最新进展　　在ASH年会上将介绍VANFLYTA®(Quizartinib)用于新诊断的FMS样酪氨酸激酶3-内部串联重复（FLT3-ITD）阳性 AML 患者的3期研究QuANTUM-First的多项子分析。其中，一项口头报告将重点分析该研究中患者共突变的频率及其对缓解率、总生存期和无复发生存期的影响。三份海报展示包括维持治疗对VANFLYTA疗效的影响，重点关注可测量残留病灶状态；临床研究检测方法对FLT3-ITD突变的检出与用下一代测序（NGS）检测可测量残留病灶之间的一致性；以及VANFLYTA与Midostaurin在新诊断的FLT3-ITD阳性AML患者中的匹配调整间接比较分析（MAIC）。　　此外，还有海报展示一项VANFLYTA联合标准化疗治疗新诊断的FLT3-ITD阴性AML患者的2期研究QUIWI的最终结果，以及关于突变状态（包括FLT3-TKD和NPM1）和ELN风险分类的其他子分析。基于QUIWI研究结果的全球多中心随机对照研究QuANTUM-Wild，将进一步评价VANFLYTA联合标准化疗在此人群的疗效。QuANTUM-Wild的研究设计将作为正在进行中的研究（TIP）通过海报重点展示。　　在ASH年会上还将展示其他两份海报数据，即一项评价Valemetostat在复发或难治性大B细胞淋巴瘤患者中的2期研究VALYM的主要结果；以及一项基于最近发表在The Lancet Oncology上的2期研究VALENTINE-PTCL01、针对循环肿瘤DNA（一种新型生物标志物）的探索性分析，以潜在预测Valemetostat在复发或难治性外周T细胞淋巴瘤患者中的临床疗效。　　　　　　　　　科技日　　　　　　　　　　　第一三共将于东部标准时间2024年12月16日星期一下午5:30至7:30/日本标准时间2024年12月17日星期二上午7:30至9:30举办投资者“科技日”（原“研发日”）活动。第一三共高管将介绍在ESMO亚洲、SABCS和ASH大会上展示的研究成果，以及研发战略。 ESMO亚洲大会、SABCS和ASH大会数据亮点　　第一三共在2024年ESMO亚洲大会上展示的DXd ADC产品组合数据亮点包括：　　第一三共在2024年SABCS上展示的DXd ADC产品组合数据亮点包括：　　第一三共在2024年ASH年会上展示的血液学产品组合数据亮点包括：　关于第一三共ADC产品组合　　　第一三共的ADC产品组合包括7款目前处于临床开发阶段的ADC，这些ADC基于第一三共内部研发的两个不同的ADC技术平台。　　目前临床开发进展最为领先的平台当属第一三共DXd AD技术平台，每AD由单克隆抗体通过可裂解四肽连接子与多个拓扑异构酶I抑制剂有效载荷（一种依喜替康衍生物，DXd）连接组成。DXd ADC产品组合目前包括靶向HER2的ADC T-DXd和靶向TROP2的ADC Dato-DXd，上述两款产品目前由第一三共与阿斯利康共同开发并在全球范围内商业化。HER3-DXd（靶向HER3的ADC）、ifinatamab deruxtecan（I-DXd，靶向 B7-H3 的ADC）、raludotatug deruxtecan（R-DXd，靶向CDH6的ADC）目前由第一三共与默沙东共同开发并在全球范围内商业化。DS-3939是一款靶向TAMUC1的ADC，目前由第一三共开发。　　第一三共的第二个ADC平台由单克隆抗体与改良吡咯并苯并二氮杂卓 (PBD) 有效载荷连接组成。DS-9606是一款靶向CLDN6的PBD ADC，是计划利用该平台进行临床开发的几款ADC中的第一款。　　Dato-DXd、I-DXd、HER3-DXd、R-DXd、DS-3939和DS-9606均为在研药物，尚未在任何国家/地区获批用于任何适应症。安全性和有效性尚未确定。关于第一三共　　第一三共是一家为社会可持续发展做贡献的创新型全球医疗保健公司，致力于发现、开发和提供新的标准疗法，以提高世界各地患者的生活质量。第一三共专注制药行业120余年，凭借其世界一流的科学和技术，为癌症、心血管疾病和其他医疗需求远未得到满足的疾病患者研发新的治疗方法和创新药物。如欲了解更多信息，请访问www.daiichisankyo.com。声明: 1.本材料不用于任何推广目的，相关信息亦不应作为治疗或使用建议。如有相关问题请咨询医疗卫生专业人士。 2.本文涉及未在中国获批的产品或适应症，第一三共不推荐任何未获批药品/适应症的使用。

临床2期临床3期临床结果引进/卖出抗体药物偶联物

2024-12-02

·Business Wire

Daiichi Sankyo Highlights Progress Across Oncology Portfolio in Multiple Solid and Blood Cancers at ESMO Asia, SABCS and ASH

BASKING RIDGE, N.J.--( BUSINESS WIRE )--Daiichi Sankyo (TSE: 4568) will present new clinical research across its oncology portfolio with more than 45 abstracts in multiple types of solid and blood cancers at the 2024 ESMO Asia Congress (#ESMOAsia24), San Antonio Breast Cancer Symposium (#SABCS24) and American Society of Hematology (#ASH24) Annual Meeting prior to its Science & Technology Day. Data at ESMO Asia, SABCS and ASH will showcase Daiichi Sankyo’s progress towards its goal of creating new standards of care for patients with cancer. Highlights include three late-breaking presentations, including a pooled analysis of data from the TROPION-Lung05 phase 2 and TROPION-Lung01 phase 3 trials of datopotamab deruxtecan (Dato-DXd) in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) at ESMO Asia, as well as a subgroup analysis from the DESTINY-Breast06 phase 3 trial of ENHERTU ® (trastuzumab deruxtecan) in patients with unresectable or metastatic HR positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer and the primary analysis from the VALENTINE phase 2 trial of patritumab deruxtecan (HER3-DXd) in patients with early HR positive, HER2 negative breast cancer at SABCS. “ Important updates in difficult-to-treat cancers including lung, breast, gastric and biliary tract cancer as well as acute myeloid leukemia and peripheral T-cell lymphoma will be highlighted at these upcoming meetings,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “ We continue to make important progress with our approved and pipeline medicines with the goal of changing the standard of care across a wide range of cancers.” Innovation in Lung, Breast, Gastric and Biliary Tract Cancer at ESMO Asia Late-breaking data at ESMO Asia will highlight a pooled analysis of results from the TROPION-Lung05 phase 2 and TROPION-Lung01 phase 3 trials of datopotamab deruxtecan in patients with previously treated EGFR-mutated advanced NSCLC during a proffered paper session. Two mini oral presentations will feature results of the TROPION-Breast01 phase 3 trial of datopotamab deruxtecan in Chinese patients with previously treated metastatic HR positive, HER2 low or negative breast cancer and the final results of the DESTINY-Gastric06 phase 2 trial of ENHERTU in Chinese patients with previously treated HER2 positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Results of DESTINY-Gastric06 led to the recent conditional approval in China of ENHERTU as a monotherapy for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received two or more prior treatment regimens. Trials-in-progress posters also will feature the trial designs of three ongoing ENHERTU clinical trials, including the DESTINY-BTC01 phase 3 trial that will evaluate ENHERTU with rilvegostomig, AstraZeneca’s PD-1/TIGIT bispecific antibody, versus standard of care in patients with previously untreated HER2 expressing, locally advanced or metastatic biliary tract cancer, and the DESTINY-Gastric03 phase 1b/2 trial where a new arm has been added to evaluate ENHERTU in combination with rilvegostomig and chemotherapy in patients with HER2 positive or HER2 low gastric or GEJ adenocarcinoma. A second part of the DESTINY-PanTumor02 phase 2 trial of ENHERTU also will be presented where patients with previously treated HER2 expressing metastatic solid tumors will be enrolled into one of five new cohorts: patients with any tumor expressing HER2 IHC 3+ (excluding breast, gastric and colorectal cancer); patients with any tumor expressing HER2 IHC 2+/ISH+ (excluding breast, gastric and colorectal cancer); patients with HER2 IHC 2+/1+ endometrial cancer; patients with HER2 IHC 2+/1+ ovarian cancer; and patients with HER2 IHC 2+/1+ cervical cancer. Continued Progress in Breast Cancer at SABCS Late-breaking presentations in breast cancer at SABCS will include two oral presentations featuring a subgroup analysis of the DESTINY-Breast06 phase 3 trial reporting on the impact of response to prior endocrine-based therapy on outcomes in patients with unresectable or metastatic HR positive, HER2 low or HER2 ultralow breast cancer who failed at least one line of endocrine therapy receiving ENHERTU compared to chemotherapy, and the primary results from the VALENTINE phase 2 trial evaluating neoadjuvant patritumab deruxtecan (HER3-DXd) alone or in combination with letrozole in patients with high-risk HR positive, HER2 negative early breast cancer. Other data at SABCS includes two spotlight poster presentations highlighting the first exploratory biomarker analysis assessing the impact of genomic alterations on the efficacy of ENHERTU compared to ado-trastuzumab emtansine (T-DM1) in patients with HER2 positive metastatic breast cancer from the DESTINY-Breast03 phase 3 trial, and the effects of ENHERTU on health-related quality of life and neurological function from the DESTINY-Breast12 phase 3b/4 trial in patients with previously treated HER2 positive metastatic breast cancer with or without brain metastases. Final results from the dose expansion portion of the DESTINY-Breast08 phase 1b trial evaluating ENHERTU in combination with capecitabine or capivasertib in patients with HER2 low metastatic breast cancer also will be presented as a poster presentation. Trial-in-progress posters will feature the trial designs from a sub-protocol of a phase 1b master protocol trial evaluating ENHERTU in combination with valemetostat, a dual EZH1 and EZH2 inhibitor, in patients with previously treated HER2 low unresectable or metastatic breast cancer as well as a phase 1b trial evaluating the combination in patients with previously treated HER2 low, HER2 ultralow or HER2 null metastatic breast cancer. Updates in Hematology Portfolio in Certain Leukemias and Lymphomas At ASH, several sub-analyses of the QuANTUM-First phase 3 trial of VANFLYTA ® (quizartinib) in patients with newly diagnosed FLT3 -ITD positive acute myeloid leukemia (AML) will be presented. An oral presentation will highlight data on the frequency of co-mutations in trial patients and their impact on remission rate, overall survival and relapse-free survival. Three poster presentations will report new data, including the impact of continuation therapy on the efficacy of VANFLYTA, focusing on measurable residual disease status; a concordance between utilizing a FLT3 -ITD mutation detection clinical trial assay and a next-generation sequencing measurable residual disease assay; and a matching adjusted indirect comparison analysis of VANFLYTA compared to midostaurin in patients with newly diagnosed FLT3 -ITD AML. Additionally, several poster presentations will report on the QUIWI phase 2 trial that evaluated VANFLYTA in combination with standard chemotherapy in patients with newly diagnosed FLT3 -ITD negative AML, including the final results of QUIWI and sub-analyses of the trial by mutational status, including FLT3 -TKD and NPM1, and ELN risk categorization. The QUIWI phase 2 trial formed the basis of the QuANTUM-Wild phase 3 trial that is further evaluating the addition of VANFLYTA to standard chemotherapy in this patient population. The design of the QuANTUM-Wild phase 3 trial will be highlighted as a trial-in-progress poster. Other data at ASH includes two poster presentations reporting the primary results of the VALYM phase 2 trial of valemetostat in patients with relapsed or refractory large B-cell lymphoma and an exploratory analysis of circulating tumor DNA, a novel biomarker, to potentially predict clinical response to valemetostat from the VALENTINE-PTCL01 phase 2 trial in patients with relapsed or refractory peripheral T-cell lymphoma, which was recently published in The Lancet Oncology . Science & Technology Day Daiichi Sankyo will hold “Science & Technology Day,” formerly called R&D Day, for investors on Monday, December 16, 2024 from 5:30 to 7:30 pm EST / Tuesday, December 17 from 7:30 to 9:30 am JST. Executives from Daiichi Sankyo will provide an overview of the ESMO Asia, SABCS and ASH research data and provide updates on R&D strategy. ESMO Asia, SABCS and ASH Data Highlights Highlights of data from Daiichi Sankyo’s DXd ADC portfolio at ESMO Asia 2024 include: Presentation Title Author Abstract Presentation (SGT) Datopotamab Deruxtecan (Dato-DXd) Lung Cancer Efficacy and safety of datopotamab deruxtecan (Dato-DXd) in patients with previously treated EGFR-mutated advanced non-small cell lung cancer: a pooled analysis of TROPION-Lung01 and TROPION-Lung05 M. Ahn LBA7 Proffered Paper Session Friday, December 6 10:15 - 11:45 am Breast Cancer Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with pre-treated inoperable/metastatic hormone receptor positive, HER2 negative breast cancer: results from TROPION-Breast01 China cohort S. Wang 38MO Mini Oral Session Saturday, December 7 2:30 - 3:40 pm ENHERTU (trastuzumab deruxtecan; T-DXd) Gastric Cancer Trastuzumab deruxtecan (T-DXd) in Chinese patients with previously treated HER2 positive advanced gastric or gastroesophageal junction adenocarcinoma: DESTINY-Gastric06 final analysis Z. Peng 129MO Mini Oral Session Saturday, December 7 9:00 - 10:40 am A phase 1b/2 open-label study evaluating trastuzumab deruxtecan (T-DXd) in combination with rilvegostomig and chemotherapy in patients with HER2 positive and HER2 low gastric or gastroesophageal junction adenocarcinoma: DESTINY-Gastric03 part 4 Y. Janjigian 264TiP Poster Session December 7, 2024 5:50 - 6:45 pm PanTumor Randomized, open-label, multicenter, phase 3 study of trastuzumab deruxtecan (T-DXd) with rilvegostomig vs standard of care in first-line HER2 expressing, locally advanced or metastatic biliary tract cancer: DESTINY-BTC01 M. Ikeda 261TiP Poster Session December 7, 2024 5:50 – 6:45 pm An open-label, multicenter, phase 2 study of trastuzumab deruxtecan (T-DXd) in patients with HER2 expressing solid tumors: DESTINY-PanTumor02 part 2 J. Lee 400TiP Poster Session December 7, 2024 5:50 – 6:45 pm Highlights of data from Daiichi Sankyo’s DXd ADC portfolio at SABCS 2024 include: Presentation Title Author Abstract Presentation (CST) ENHERTU (trastuzumab deruxtecan; T-DXd) HER2 Low & HER2 Ultralow Breast Cancer Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy by pace of disease progression on prior endocrine-based therapy: an additional analysis from DESTINY-Breast06 A Bardia LB1-04 Oral Session Tuesday, December 10 6:00 – 7:00 pm Trastuzumab deruxtecan in combination with capecitabine or capivasertib in patients with HER2 low metastatic breast cancer: a phase 1b, multicenter, open-label study (DESTINY-Breast08) K. Jhaveri P3-09-17 Poster Session Thursday, December 12 12:30 - 2:00 pm A real-world study of the effectiveness and safety of trastuzumab deruxtecan in HER2 low metastatic breast cancer among racial and ethnic minorities and older populations in the United States M. Henderson P2-12-20 Poster Session Wednesday, December 11 5:30 - 7:00 pm Agreement between the DESTINY-Breast04/06 VENTANA 4B5 HER2 IHC clinical trial assay and other comparator assays for HER2 low breast cancer: overall results of a large-scale, multicenter global ring study G. Viale P1-03-28 Poster Session Wednesday, December 11 12:30 - 2:00 pm Trastuzumab deruxtecan in HER2 low metastatic breast cancer patients with newly diagnosed or progressing brain metastases: the TUXEDO-4 phase II trial M. Marhold P3-08-21 Poster Session Thursday, December 12 12:30 - 2:00 pm Re-evaluation of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 0 or 1+ in metastatic breast cancer samples to characterize the proportion of HER2 ultralow (IHC 0 with membrane staining) S. Krishnamurthy P3-09-20 Poster Session Thursday, December 12 12:30 – 2:00 pm Valemetostat and trastuzumab deruxtecan in patients with HER2 low, previously treated, unresectable or metastatic breast cancer S. Tolaney P3-08-24 Poster Session Thursday, December 12 12:30 - 2:00 pm Phase 1b study of EZH1/2 inhibitor valemetostat in combination with trastuzumab deruxtecan in subjects with HER2 low/ultra-low/null metastatic breast cancer T. Iwase P3-12-28 Poster Session Thursday, December 12 12:30 - 02:00 pm HER2 Positive Breast Cancer Exploratory biomarker analysis of trastuzumab deruxtecan vs trastuzumab emtansine efficacy in human epidermal growth factor receptor 2-positive metastatic breast cancer in DESTINY-Breast03 W. Jacot PS8-03 Spotlight Poster Session Thursday, December 12 7:00 - 8:30 am Effects of trastuzumab deruxtecan (T-DXd) on health-related quality of life and neurological function in patients with HER2+ advanced/metastatic breast cancer with or without brain metastases: DESTINY-Breast12 results N. Harbeck PS14-10 Spotlight Poster Session Friday, December 13 7:00 – 8:30 am Real-world analysis of interstitial lung disease in patients with HER2-positive unresectable or recurrent breast cancer treated with trastuzumab deruxtecan: all-patient post-marketing surveillance study in Japan J. Tsurutani P1-02-10 Poster Session Wednesday, December 11 12:30 – 2:00 pm HER2 Expressing Breast Cancer Trastuzumab deruxtecan with pembrolizumab in previously treated HER2 expressing advanced or metastatic breast cancer: interim analyses of the breast cohorts from the open-label, multicenter, phase 1b study DS8201-A-U106 H. Rugo P5-07-29 Poster Session Friday, December 13 12:30 - 2:00 pm Patritumab Deruxtecan (HER3-DXd) HR Positive, HER2 Negative Breast Cancer Primary results of SOLTI VALENTINE: neoadjuvant randomized phase II trial of HER3-DXd alone or in combination with letrozole for high-risk hormone receptor positive/HER2-negative early breast cancer M. Oliveira LBA1-06 Oral Presentation Tuesday, December 10 6:00 - 7:00 pm ICARUS-BREAST02: safety, tolerability, and anti-tumor activity of patritumab deruxtecan (HER3-DXd) monotherapy and combinations in patients with inoperable advanced breast cancer following progression on trastuzumab deruxtecan (T-DXd) B. Pistilli P2-08-27 Poster Presentation Wednesday, December 11 5:30 - 7:00 pm Highlights of data from Daiichi Sankyo’s hematology portfolio at ASH 2024 include: Presentation Title Author Abstract Presentation (PST) VANFLYTA (quizartinib) FTL3 -ITD Positive AML Correlation of baseline gene mutations with quizartinib efficacy in patients with FLT3 -ITD positive newly diagnosed acute myeloid leukemia in the phase 3 QuANTUM-First trial M. Levis 848 Oral Presentation Monday, December 9 3:00 - 3:15 pm QuANTUM-First: effects of quizartinib on RFS, OS, CIR, and MRD in newly diagnosed patients with FMS-like tyrosine kinase 3-internal tandem duplication positive ( FLT3 -ITD+) acute myeloid leukemia who received continuation therapy M. Levis 2890 Poster Presentation Sunday, December 8 6:00 - 8:00 pm QuANTUM-First: deep-dive analysis of FMS-like tyrosine kinase 3-internal tandem duplication ( FLT3 -ITD) detection methods utilized for enrollment and longitudinal MRD detection in newly diagnosed patients with FLT3 -ITD+ acute myeloid leukemia J. Rohrbach 4278 Poster Session Monday, December 9 6:00 - 8:00 pm Anchored matching adjusted indirect treatment comparison of quizartinib vs midostaurin in newly diagnosed patients with FLT3 -ITD positive acute myeloid leukemia S. Unni 1509 Poster Session Saturday, December 7 5:30 - 7:30 pm FLT3 -ITD Negative AML Trial in progress: the phase 3, randomized, double-blind, placebo-controlled QuANTUM-Wild study of quizartinib in combination with chemotherapy and as single-agent maintenance in newly diagnosed FLT3 -ITD negative acute myeloid leukemia P. Montesinos 1504.3 Poster Session Saturday, December 7 5:30 – 7:30 pm Final results of QUIWI: a double blinded, randomized PETHEMA trial comparing standard chemotherapy plus quizartinib versus placebo in adult patients with newly diagnosed FLT3 -ITD negative AML P. Montesinos 1512 Poster Session Saturday, December 7 5:30 - 7:30 pm Enhanced validation of the FLT3 -like gene expression signature as a predictive biomarker for quizartinib response in FLT3 -ITD negative acute myeloid leukemia: expanded cohort and extended follow-up from the PETHEMA QUIWI trial A. Mosquera Orgueira 1552 Poster Session Saturday, December 7 5:30 - 7:30 pm Correlation of ELN-risk and gene mutations with quizartinib efficacy in patients with FLT3 -ITD negative newly diagnosed acute myeloid leukemia in the phase 2 QUIWI PETHEMA trial R. Rodriguez- Viega 2895 Poster Session Sunday, December 8 6:00 - 8:00 pm Valemetostat (EZHARMIA in Japan only) B-Cell & T-Cell Lymphomas Valemetostat monotherapy in patients with relapsed or refractory large B-cell lymphoma: primary results of the phase 2 VALYM study from the LYSA E. Bachy 4479 Poster Session Monday, December 9 6:00 - 8:00 pm Prediction of clinical response by phased variants in circulating tumor DNA (ctDNA) in the VALENTINE-PTCL01 trial of patients with relapsed or refractory peripheral T-cell lymphoma N. Mehta-Shah 4342 Poster Session Monday, December 9 6:00 - 8:00 pm About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical needs. For more information, please visit www.daiichisankyo.com .

临床2期临床3期临床结果临床1期ASH会议

100 项与奎扎替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	奎扎替尼	L01XE52	DB12874

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
急性髓性白血病	英国	Daiichi Sankyo UK Ltd.	2024-03-12
伴有 FLT3/ITD 突变的急性髓系白血病	日本	Daiichi Sankyo Co., Ltd.	2019-06-18

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肿瘤	申请上市	加拿大	第一三共制药（上海）有限公司	2024-08-01
FLT3阳性急性髓性白血病	临床3期	美国	Daiichi Sankyo, Inc.	2014-05-01
FLT3阳性急性髓性白血病	临床3期	澳大利亚	Daiichi Sankyo, Inc.	2014-05-01
FLT3阳性急性髓性白血病	临床3期	比利时	Daiichi Sankyo, Inc.	2014-05-01
FLT3阳性急性髓性白血病	临床3期	加拿大	Daiichi Sankyo, Inc.	2014-05-01
FLT3阳性急性髓性白血病	临床3期	克罗地亚	Daiichi Sankyo, Inc.	2014-05-01
FLT3阳性急性髓性白血病	临床3期	捷克	Daiichi Sankyo, Inc.	2014-05-01
FLT3阳性急性髓性白血病	临床3期	法国	Daiichi Sankyo, Inc.	2014-05-01
FLT3阳性急性髓性白血病	临床3期	德国	Daiichi Sankyo, Inc.	2014-05-01
FLT3阳性急性髓性白血病	临床3期	中国香港	Daiichi Sankyo, Inc.	2014-05-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02668653 (QuANTUM-First, ASH2024)	临床3期	FLT3阳性急性髓性白血病 FLT3-ITD-positive \| NPM1 \| CEBPA ... 更多	518	Quizartinib	淵製衊衊鹽獵製網淵廠(淵積餘鏇襯構鬱餘觸築) = 窪廠憲蓋獵簾選廠鏇鬱鹽網衊繭蓋餘憲壓遞製 (網鹹壓衊醖構獵餘夢築 ) 更多	积极	2024-12-09
				Placebo	淵製衊衊鹽獵製網淵廠(淵積餘鏇襯構鬱餘觸築) = 顧積淵膚醖鏇醖憲遞壓鹽網衊繭蓋餘憲壓遞製 (網鹹壓衊醖構獵餘夢築 ) 更多
ASH2024	N/A	伴有 FLT3/ITD 突变的急性髓系白血病	-	Quizartinib	膚獵積蓋憲觸廠繭壓艱(鹹築壓願構糧獵願襯鑰) = In the R/R cohort, grade ≥3 non-hematologic toxicities regardless of attribution, in >10% of pts, included pneumonia (73%), neutropenic fever (53%), sepsis (18%), other infections involving the skin (18%)bacteremia (15%), and gastrointestinal tract (13%), with 8% experiencing grade 3 QTcF prolongations. Grade ≥3 non-hematologic toxicities was less common in the frontline cohort, with pneumonia (40%), neutropenic fever (50%), sepsis (10%), bacteremia (20%), and no grade 3 QTcF prolongations observed. 獵願餘襯簾繭構壓齋鬱 (窪鏇襯衊糧廠餘窪鹽鹽 )	-	2024-12-09
				Venetoclax
ASH2024	N/A	FLT3阳性急性髓性白血病	-	Quizartinib	範夢鹽餘齋憲憲壓淵觸(鏇衊觸艱鬱艱網醖膚構) = 選窪襯繭鑰範蓋襯鏇顧鹽製繭淵願蓋觸襯窪艱 (鏇簾積蓋憲醖鑰獵艱範 ) 更多	-	2024-12-08
				Placebo	範夢鹽餘齋憲憲壓淵觸(鏇衊觸艱鬱艱網醖膚構) = 艱膚選壓憲鑰鬱鏇夢鹽鹽製繭淵願蓋觸襯窪艱 (鏇簾積蓋憲醖鑰獵艱範 ) 更多
NCT04493138 (Pubmed) 人工标引	临床1期	骨髓增生性疾病 \| 骨髓增生异常综合征 CBL Mutation \| FLT3 Mutation	12	Azacitidine + Quizartinib 30mg	憲製簾憲廠憲繭鑰衊淵(憲鏇鬱鬱壓繭糧鏇鹽醖) = thrombocytopenia (n=5, 42 %), anemia (n=4, 33 %), lung infection (n=2, 17 %), skin infection (n=2, 17 %), hyponatremia (n=2, 17 %) and sepsis (n=2, 17 %). 積鏇網鑰選衊繭蓋膚淵 (夢膚膚願糧構顧窪夢鏇 ) 更多	积极	2024-07-01
NCT02668653 (QuANTUM-First, EHA2024) 人工标引	临床3期	伴有 FLT3/ITD 突变的急性髓系白血病一线 FLT3-ITD positive	208	Quizartinib (Q)	構構簾膚鬱製夢鹹蓋網(蓋鑰艱構鹹醖窪繭網衊) = 積齋襯鹹製壓獵鏇蓋憲襯積繭憲艱構繭窪網憲 (餘製願構顧鬱鹽範製簾 ) 更多	积极	2024-05-14
				Placebo (P)	構構簾膚鬱製夢鹹蓋網(蓋鑰艱構鹹醖窪繭網衊) = 廠鬱選壓製襯簾衊鹹遞襯積繭憲艱構繭窪網憲 (餘製願構顧鬱鹽範製簾 ) 更多
NCT02668653 (QuANTUM-First, EHA2024) 人工标引	临床3期	伴有 FLT3/ITD 突变的急性髓系白血病一线 \| 诱导 \| 巩固 FLT3-ITD+	533	Quizartinib (Q)	醖範築鬱鏇夢製襯鹹鏇(製鹽鑰獵夢觸獵糧齋艱) = Infections were the most common serious TEAEs (TESAEs), in all phases 遞糧鹹醖積簾衊願鑰衊 (鹹窪鹽夢構壓衊獵窪壓 ) 更多	积极	2024-05-14
				Placebo (P)
NCT02668653 (QuANTUM-First, EHA2024) 人工标引	临床3期	伴有 FLT3/ITD 突变的急性髓系白血病一线 \| 诱导 FLT3-ITD+	539	Quizartinib (Q)	觸遞遞鹽壓艱鹹願觸鹽(簾網遞膚鑰製鹹鬱衊遞) = 鹽範壓遞鑰膚網構觸襯積夢積積觸鏇鑰壓襯窪 (夢餘憲製廠蓋窪壓獵獵 ) 更多	积极	2024-05-14
				Placebo (P)	觸遞遞鹽壓艱鹹願觸鹽(簾網遞膚鑰製鹹鬱衊遞) = 艱壓艱齋繭壓壓選鑰艱積夢積積觸鏇鑰壓襯窪 (夢餘憲製廠蓋窪壓獵獵 ) 更多
NCT01892371 (CTgov)	临床1/2期	复发性急性髓细胞白血病 \| 慢性粒单核细胞白血病 \| 难治性骨髓增生异常综合征 ... 更多	73	Quizartinib+Azacitidine (Phase 1 Arm I (Quizartinib, Azacitidine))	顧夢糧蓋艱遞簾鏇繭艱(網憲壓顧築鏇繭遞齋製) = 膚襯淵鏇製鹹願獵繭構齋顧繭餘構壓廠製衊膚 (範構淵壓範鬱鬱襯鏇蓋, 鑰鹹積醖襯製觸顧衊獵 ~ 構鬱鬱醖觸壓獵鑰餘廠) 更多	-	2024-02-28
				Quizartinib+Cytarabine (Phase 1 Arm II (Quizartinib, Cytarabine))	顧夢糧蓋艱遞簾鏇繭艱(網憲壓顧築鏇繭遞齋製) = 憲齋範顧選獵鏇範築襯齋顧繭餘構壓廠製衊膚 (範構淵壓範鬱鬱襯鏇蓋, 憲鹽齋襯憲網窪遞憲積 ~ 遞構衊淵網壓膚襯觸窪) 更多
CHIP-AML22 (ASH2023)	N/A	急性髓性白血病 \| 伴有 FLT3/ITD 突变的急性髓系白血病	905	Quizartinib + chemotherapy	鑰壓鑰憲膚憲鏇鏇獵觸(構獵觸壓醖繭範醖淵鏇) = 膚範願積簾鑰餘廠壓壓選鏇壓選鹹構繭鬱醖襯 (觸遞繭夢遞遞膚鹹觸醖 ) 更多	-	2023-12-09
ASH2023	临床1/2期	伴有 FLT3/ITD 突变的急性髓系白血病	50	Quizartinib	壓鬱壓鹽餘鬱鑰選網壓(簾製遞簾壓糧憲鬱觸廠) = 艱齋齋壓餘構糧簾構獵觸築選遞築淵製築遞製 (壓選餘齋顧鏇糧積醖衊 ) 更多	-	2023-12-09
				Venetoclax	蓋壓顧積願範繭選顧醖(窪獵網遞鏇艱蓋鑰壓壓) = 鹹簾積廠築憲膚膚獵觸構艱鬱窪繭繭艱鏇選窪 (製壓選鑰構廠鬱壓艱窪 )