A Phase Ib/II, Dose Escalation and Dose Expansion Study of Valemetostat Tosylate (DS-3201b) with Atezolizumab and Bevacizumab in Advanced Hepatocellular Carcinoma (HCC)

This is a phase Ib/II, dose escalation and dose expansion study of valemetostat (DS-3201) with atezolizumab and bevacizumab in patients advanced Hepatocellular carcinoma (HCC) who did not receive prior systemic therapy for advanced HCC.

Start Date31 Dec 2024

Sponsor / Collaborator

The University of Alabama at Birmingham

NCT05879484 / Not yet recruitingPhase 1/2IIT

A Phase Ib/II Multicenter Study of Front Line Pembrolizumab and Valemetostat in PD-L1 Positive, HPV-Negative Recurrent/Metastatic Squamous Cell Carcinoma (SCC) of the Head and Neck: The PANTHERAS

Background:
Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. These cancers have different causes, with smoking/tobacco exposure and human papilloma virus infection being the most common. . When HNSCC occurs in people who are not infected with HPV, the cancers are more likely to return after treatment; when this happens, overall survival is only about 10 months, thus better treatments are needed.
Objective:
To test a combination treatment using 2 drugs (valemetostat and pembrolizumab) in people with HNSCC. Phase 1b of the study will determine a recommended dose of the 2 drugs and evaluate how safe the combination is.; this will include patients with HPV-positive and HPV-negative HNSCC, as well as squamous cell NSCLC that have progressed on anti-PD-1/anti-PD-L1 therapies.Phase II will determine how effective the combination is and will focus on patients with HPV-negative HNSCC.
Eligibility:
People aged 18 years and older with HPV-negative HNSCC, sinonasal carcinoma of the head and neck, or squamous non-small cell lung cancer (NSCLC).
Design:
Participants will be screened. They will have a physical exam. They will have blood and urine tests and tests of their heart function. They will have imaging scans. They may have a biopsy: A small sample of tissue will be removed from the tumor.
Treatment will be given in 21-day cycles.
Pembrolizumab is administered through a tube attached to a needle inserted into a vein in the arm. Participants will receive pembrolizumab on the first day of each cycle.
Valemetostat is a tablet taken by mouth. Participants will take the tablet once a day at home. They will record the date and time of each dose in a diary. They will also write down any adverse effects they experience.
Participants may remain in the study up to 2 years.

Start Date09 Dec 2024

Sponsor / Collaborator

National Cancer Institute

NCT06644768 / RecruitingPhase 1/2

A Multicenter, Randomized, Open-Label, Phase 1b/2 Trial Of Valemetostat Tosylate Plus Pembrolizumab Vs Pembrolizumab Alone in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Whose Tumors Express PD-L1 With Tumor Proportion Score ≥50% Without Actionable Genomic Alterations

This study will compare Valemetostat Tosylate Plus Pembrolizumab vs Pembrolizumab Alone in First-line NSCLC Without Actionable Genomic Alterations

Start Date30 Oct 2024

Sponsor / Collaborator

Daiichi Sankyo Co., Ltd.

[+1]

100 Clinical Results associated with Valemetostat Tosilate

100 Translational Medicine associated with Valemetostat Tosilate

100 Patents (Medical) associated with Valemetostat Tosilate

Literatures (Medical) associated with Valemetostat Tosilate

01 Dec 2024·LANCET ONCOLOGY

Valemetostat monotherapy in patients with relapsed or refractory non-Hodgkin lymphoma: a first-in-human, multicentre, open-label, single-arm, phase 1 study

Article

Author: Feldman, Tatyana ; Brammer, Jonathan E ; Foss, Francine ; Ishitsuka, Kenji ; Narita, Tomoko ; Morishima, Satoko ; Tsukasaki, Kunihiro ; Kusumoto, Shigeru ; Yuda, Junichiro ; Yamauchi, Nobuhiko ; Zain, Jasmine ; Wang, Jie ; Hizukuri, Yoshiyuki ; Allen, Pamela ; Kakurai, Yasuyuki ; Nosaka, Kisato ; Izutsu, Koji ; Imaizumi, Yoshitaka ; Utsunomiya, Atae ; Porcu, Pierluigi ; Biserna, Noha ; Horwitz, Steven M ; Ruan, Jia ; Tobinai, Kensei ; Yamauchi, Hideyuki ; Tachibana, Masaya ; Jacobsen, Eric ; Inoue, Ai ; Maruyama, Dai ; Kawamata, Toyotaka

BACKGROUND:

Few treatment options exist for patients with non-Hodgkin lymphoma, and outcomes remain poor for relapsed or refractory disease. We evaluated the safety and preliminary clinical activity of valemetostat, a novel inhibitor of EZH2 and EZH1, in patients with relapsed or refractory non-Hodgkin lymphomas.

METHODS:

This first-in-human, multicentre, open-label, single-arm, phase 1, dose-escalation and dose-expansion trial was done in 19 hospitals across Japan and the USA. Patients were included if they were aged 18 years or older in the USA or 20 years or older in Japan with a primary diagnosis of relapsed or refractory non-Hodgkin lymphoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. In the dose-escalation part, patients received oral valemetostat at doses of 150 mg per day, 200 mg per day, 250 mg per day, and 300 mg per day continuously in 28-day cycles until progressive disease or unacceptable toxicities. All patients received 200 mg per day in the dose-expansion part. The primary endpoints were safety, pharmacokinetics, and the recommended phase 2 dose; the secondary endpoints were the maximum tolerated dose and the antitumour activity of valemetostat. Responses were assessed in patients who received at least one dose, with measurable lesions at baseline according to the International Working Group 2007 revised criteria for malignant lymphoma (peripheral T-cell lymphoma and B-cell non-Hodgkin lymphoma) and the modified 2009 criteria for adult T-cell leukaemia/lymphoma. The trial is registered with ClinicalTrials.gov, NCT02732275, and is currently active, but not recruiting.

FINDINGS:

Between April 7, 2016, and June 10, 2021, 90 patients (53 [59%] males and 37 [41%] females; 49 [54%] Asian, 33 [37%] White, and eight [9%] Black) were enrolled and treated with valemetostat and included in the safety analysis set. 57 (63%) patients had peripheral T-cell lymphoma, 14 (16%) had adult T-cell leukaemia/lymphoma, and 19 (21%) had B-cell non-Hodgkin lymphoma. Seven (8%) patients received valemetostat 150 mg per day, 74 (82%) received 200 mg per day, seven received 250 mg per day, and two received 300 mg per day. Median follow-up was 7·4 months (IQR 3·4-17·6). All patients had at least one treatment-emergent adverse event; the most common treatment-emergent adverse events of any grade were decreased platelet count (52 [58%] of 90 patients), dysgeusia (45 [50%]), and anaemia (38 [42%]). The most common grade 3-4 adverse events were decreased neutrophil count (21 [23%]), decreased platelet count (18 [20%]), and decreased lymphocyte count (17 [19%]). The most common serious adverse event of any grade was Pneumocystis jirovecii pneumonia (four [4%]). No treatment-related deaths occurred. The overall response rate was 54·5% (48 of 88; 95% CI 43·6-65·2) for patients in the efficacy analysis set. The maximum tolerated dose was not reached; the recommended phase 2 dose of 200 mg per day was determined. Valemetostat exposure was variable between patients and was overlapped over the dose range of 150-250 mg per day.

INTERPRETATION:

The safety profile of valemetostat monotherapy was acceptable in these patients with relapsed or refractory non-Hodgkin lymphoma. Favourable clinical activity was observed. These findings support a new indication for valemetostat in this setting.

FUNDING:

Daiichi Sankyo.

01 Dec 2024·LANCET ONCOLOGY

Valemetostat for patients with relapsed or refractory peripheral T-cell lymphoma (VALENTINE-PTCL01): a multicentre, open-label, single-arm, phase 2 study

Article

Author: Cwynarski, Kate ; Moriyama, Takaya ; Feldman, Tatyana ; Yoon, Dok Hyun ; Gritti, Giuseppe ; Ishitsuka, Kenji ; Jacobsen, Eric ; Zinzani, Pier Luigi ; Kusumoto, Shigeru ; Mehta-Shah, Neha ; Jin, Jin ; Ennishi, Daisuke ; Wu, Sutan ; Kim, Jin Seok ; Domenech, Eva Domingo ; Córdoba, Raul ; Zain, Jasmine ; Chen, Yang ; Wang, Jie ; Horwitz, Steven M ; Guillermin, Yann ; Nakajima, Keiko ; Bachy, Emmanuel ; Barta, Stefan K ; Izutsu, Koji ; Prica, Anca ; Poel, Marjolein van der ; Inoue, Ai

BACKGROUND:

Peripheral T-cell lymphomas are aggressive non-Hodgkin lymphomas with few treatment options for relapsed or refractory disease. Valemetostat tosylate (valemetostat) is a potent, novel, dual inhibitor of EZH2 and EZH1. We investigated the clinical activity and safety of valemetostat in patients with relapsed or refractory peripheral T-cell lymphoma, and its safety in patients with relapsed or refractory adult T-cell leukaemia/lymphoma.

METHODS:

VALENTINE-PTCL01 was a multicentre, open-label, single-arm, phase 2 trial performed at 47 hospitals in 12 countries across Asia, Europe, North America, and Oceania. Patients with either peripheral T-cell lymphoma or adult T-cell leukaemia/lymphoma, aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2 received oral valemetostat at 200 mg per day in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint for patients with peripheral T-cell lymphoma was the CT-based objective response rate by blinded independent central review (BICR) using 2014 Lugano response criteria. Patients who received valemetostat and had a confirmed eligible peripheral T-cell lymphoma subtype on central review were included in the efficacy analysis. The primary endpoint for patients with adult T-cell leukaemia/lymphoma was the safety and tolerability of valemetostat. Safety in both cohorts was assessed in all patients who received at least one dose of valemetostat. The trial is registered with ClinicalTrials.gov, NCT04703192, and EudraCT, 2020-004954-31, and is closed to enrolment.

FINDINGS:

Between June 16, 2021, and Aug 10, 2022, 133 patients with relapsed or refractory peripheral T-cell lymphoma (median age 69·0 years [IQR 58·0-74·0]; 91 [68%] were male, and 42 [32%] were female) and 22 patients with adult T-cell leukaemia/lymphoma (66·5 years [54·0-73·0]; 15 [68%] were male, and seven [32%] were female) were enrolled. The median follow-up time was 12·3 months (95% CI 11·8-13·8). 52 (44%; 95% CI 35-53) of 119 efficacy-evaluable patients with relapsed or refractory peripheral T-cell lymphoma had an objective response. The most common grade 3-4 adverse events were thrombocytopenia (31 [23%] of 133 patients in the peripheral T-cell lymphoma group and 11 [50%] of 22 patients in the adult T-cell leukaemia/lymphoma group), anaemia (25 [19%] and ten [46%]), and neutropenia (23 [17%] and four [18%]). Serious treatment-emergent adverse events were reported in 53 (40%) patients with peripheral T-cell lymphoma and 15 (68%) patients with adult T-cell leukaemia/lymphoma; nine (7%) patients and one (5%) patient had a serious treatment-emergent adverse event considered to be treatment related, respectively. No treatment-related deaths were reported.

INTERPRETATION:

These data show that treatment with valemetostat leads to durable responses in patients with relapsed or refractory peripheral T-cell lymphoma, with a manageable safety profile.

FUNDING:

Daiichi Sankyo.

14 Oct 2024·LEUKEMIA & LYMPHOMA

Adult T-cell leukemia-lymphoma with neurolymphomatosis successfully controlled by valemetostat: a case report and review of literature

Article

Author: Shimura, Arika ; Baba, Yusuke ; Tsujita, Masahiko ; Toho, Masanori ; Maekawa, Hiroki ; Sumi, Kensyo ; Yoshioka, Reo ; Hamada, Masashi ; Kurokawa, Mineo ; Kimura, Tomohiko ; Muramatsu, Kyosuke ; Toda, Tatsushi ; Masuda, Yasutaka ; Masamoto, Yosuke ; Yasunaga, Megumi ; Mitsuchi, Shuichiro

Adult T cell leukemia-lymphoma (ATL) represents a rare and aggressive hematol. malignancy provoked by human t-cell lymphotropic virus type 1 (HTLV-1).Neurolymphomatosis involves nerve roots within or beyond the boundaries of the subarachnoid space, hence intrathecal chemotherapy and radiation therapy will not address all lesions, necessitating systemic chemotherapy to manage the multiple lesions.The most effective treatment for neurolymphomatosis remains uncertain, and the choice of treatment has often been based on regimens for CNS lymphomas.Valemetostat, a novel dual inhibitor of enhancer of zeste homolog 1 (eZh1) and eZh2, has demonstrated efficacy in relapsed or refractory AtL in phase I/II clin. trials.Documented here is a case of a septuagenarian man afflicted with acute type AtL who exhibited CNS and peripheral nerve involvement subsequent to multiple chemotherapies and was effectively managed with valemetostat.The case underscores the importance of considering valemetostat as a therapeutic option for CNS infiltration and neurolymphomatosis in AtL.Further investigations are warranted to elucidate the efficacy and safety of valemetostat in AtL with CNS involvement and/ or neurolymphomatosis.

News (Medical) associated with Valemetostat Tosilate

02 Dec 2024

·www.businesswire.com

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 .

Phase 2Phase 3Clinical ResultPhase 1ASH

04 Sep 2024

·www.businesswire.com

Daiichi Sankyo Unveils New Research Across Industry-Leading ADC Portfolio in Multiple Cancers at WCLC and ESMO

BASKING RIDGE, N.J.--( BUSINESS WIRE )--Daiichi Sankyo (TSE: 4568) will present new clinical research across its antibody drug conjugate (ADC) portfolio with more than 25 abstracts across multiple types of cancer at the IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC24) and the 2024 European Society for Medical Oncology (#ESMO24). Data at WCLC and ESMO showcasing Daiichi Sankyo’s progress towards its goal of creating new standards of care for patients with cancer will include six late-breaking presentations, including two back-to-back presentations during Presidential Symposium 1 featuring datopotamab deruxtecan (Dato-DXd) data at WCLC, and the first presentation of clinical data of DS-9606, a CLDN6 directed modified pyrrolobenzodiazepine (PBD) ADC from Daiichi Sankyo’s second ADC platform, at ESMO. “ New data in lung, breast, gastric, ovarian, endometrial and other cancers from several of our DXd antibody drug conjugates demonstrates how we are making substantial progress toward creating new standards of care for patients with cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “ We look forward to presenting initial clinical data from our second antibody drug conjugate platform at ESMO, which underscores how Daiichi Sankyo is applying our expertise in this technology to craft new innovation for patients.” Progress in Lung Cancer at WCLC and ESMO Late-breaking data at WCLC to be reported during back-to-back presentations at Presidential Symposium 1 will highlight the first interim results from the NeoCOAST-2 phase 2 platform trial evaluating novel perioperative treatment combinations including one arm studying datopotamab deruxtecan with durvalumab and chemotherapy as neoadjuvant treatment followed by adjuvant treatment with durvalumab in patients with resectable early-stage (IIA to IIIB) non-small cell lung cancer (NSCLC). The second Presidential Symposium 1 presentation will feature results from the application of quantitative continuous scoring (QCS), AstraZeneca’s proprietary computational pathology platform, to measure TROP2 in tissue samples collected in the TROPION-Lung01 phase 3 trial that evaluated datopotamab deruxtecan versus docetaxel in patients with locally advanced or metastatic NSCLC treated with at least one prior line of therapy. Overall survival results from TROPION-Lung01 also will be presented as a late-breaking oral presentation. Other data at WCLC include two oral presentations featuring the interim results from the dose optimization part of the IDeate-Lung01 phase 2 trial of ifinatamab deruxtecan (I-DXd) in patients with pretreated extensive-stage small cell lung cancer and results from the ENHERTU ® (trastuzumab deruxtecan) monotherapy arm of the DESTINY-Lung03 phase 1b trial in patients with previously treated HER2 overexpressing unresectable, locally advanced or metastatic NSCLC. A trial-in-progress poster from the NSCLC cohort of a phase 1b trial evaluating the combination of datopotamab deruxtecan and valemetostat, a dual inhibitor of EZH1 and EZH2, in previously treated locally advanced, unresectable or metastatic nonsquamous NSCLC with or without actionable genomic alterations also will be highlighted. At ESMO, additional data in lung cancer being reported include poster presentations featuring a post-hoc analysis of patients with nonsquamous NSCLC by baseline brain metastases status in the TROPION-Lung01 phase 3 trial of datopotamab deruxtecan and intracranial responses seen in the IDeate-Lung01 phase 2 trial of ifinatamab deruxtecan, as well as a trial-in-progress poster featuring the design of the IDeate-Lung03 phase 1b/2 trial of ifinatamab deruxtecan in combination with atezolizumab with or without carboplatin as first-line induction or maintenance therapy in patients with extensive-stage small cell lung cancer. Continued Innovation in Breast Cancer at ESMO Late-breaking presentations in breast cancer at ESMO will include a proffered paper session featuring the primary results of the DESTINY-Breast12 phase 3b/4 trial evaluating ENHERTU in patients with HER2 positive advanced or metastatic breast cancer with or without brain metastases, and two mini oral sessions highlighting patient reported outcomes and determination of the HER2 low and HER2 ultralow status of tumors from the DESTINY-Breast06 phase 3 trial in patients with HR positive, HER2 low and HER2 ultralow metastatic breast cancer. Two proffered paper sessions will highlight results from the ICARUS-BREAST01 phase 2 study of patritumab deruxtecan (HER3-DXd) in patients with HR positive, HER2 negative advanced breast cancer with disease progression following two or more treatments and the investigator-initiated ERICA phase 2 trial evaluating olanzapine-based triplet antiemetic therapy for prevention of nausea and vomiting in combination with ENHERTU in patients with metastatic breast cancer. A mini oral session will feature a supplementary biomarker analysis from the DAISY phase 2 trial evaluating ENHERTU in three cohorts of patients with HER2 expressing metastatic breast cancer and a poster presentation will report on an exploratory biomarker analysis of ENHERTU in patients with HR positive, HER2 low metastatic breast cancer from the DESTINY-Breast04 phase 3 trial. A poster reporting on exposure-adjusted incidence rates of adverse events from the TROPION-Breast01 phase 3 trial of datopotamab deruxtecan versus chemotherapy in patients with previously treated HR positive, HER2 negative metastatic breast cancer also will be featured. Data from Daiichi Sankyo’s Second ADC Platform and DXd ADC Data in Multiple Additional Cancers at ESMO At ESMO, a proffered paper session will highlight preliminary results from a phase 1 trial of DS-9606, a CLDN6 directed modified PBD ADC from Daiichi Sankyo’s second ADC platform, in patients with solid tumors known to express CLDN6. Results from the DESTINY-Gastric03 phase 1b/2 trial evaluating ENHERTU monotherapy or ENHERTU combinations with chemotherapy and/or immunotherapy in patients with HER2 expressing advanced/metastatic gastric or gastroesophageal junction carcinoma also will be presented at a proffered paper session. A mini oral session will feature results from the TROPION-PanTumor03 phase 2 trial of datopotamab deruxtecan in patients with previously treated recurrent endometrial or ovarian cancer. Trial-in-progress poster presentations will highlight the HERTHENA-PanTumor01 phase 2 trial evaluating patritumab deruxtecan in patients with a broad range of solid tumors including bladder, cervical, endometrial, esophageal, gastric, head and neck, melanoma, ovarian, pancreatic and prostate and a phase 1 trial of DS-1471, a CD147 monoclonal antibody, in patients with locally advanced or metastatic solid cancers. Investor Conference Call Following ESMO Daiichi Sankyo will hold a virtual conference call for investors on Tuesday, September 17, 2024 from 8:00 to 9:30 am EDT / 9:00 to 10:30 pm JST. Executives from Daiichi Sankyo will provide an overview of the WCLC and ESMO research data and address questions. WCLC and ESMO Data Highlights Highlights of data from Daiichi Sankyo’s ADC portfolio at WCLC 2024 include: Presentation Title Author Abstract Presentation (PDT) NSCLC NeoCOAST-2: efficacy and safety of neoadjuvant durvalumab (D) + novel anticancer agents + CT and adjuvant D ± novel agents in resectable NSCLC T. Cascone PL02.07 Presidential Symposium 1 Sunday, September 8 8:30 - 10:00 am Normalized membrane ratio of TROP2 by quantitative continuous scoring is predictive of clinical outcomes in TROPION-Lung01 M.C. Garassino PL02.11 Presidential Symposium 1 Sunday, September 8 8:30 - 10:00 am Datopotamab deruxtecan vs docetaxel in patients with non-small cell lung cancer: final overall survival from TROPION-Lung01 J. Sands OA08.03 Oral Presentation Monday, September 9 10:45 - 12:00 pm Trastuzumab deruxtecan monotherapy in pretreated HER2 overexpressing nonsquamous non-small cell lung cancer: DESTINY-Lung03 part 1 D. Planchard OA16.05 Oral Presentation Tuesday, September 10 1:30 - 2:45 pm Valemetostat and datopotamab deruxtecan in previously treated, advanced, unresectable, or metastatic non-squamous NSCLC A. Spira P2.10A.04 Poster Session Sunday, September 8 6:15 - 7:45 pm SCLC Ifinatamab deruxtecan (I-DXd) in extensive-stage small cell lung cancer (ES-SCLC): interim analysis of IDeate-Lung01 C. Rudin OA04.03 Oral Presentation Sunday, September 8 2:00 - 3:15 pm Exposure-response analyses to support phase 3 dose selection for I-DXd (ifinatamab deruxtecan) in extensive stage SCLC patients N. Midde P1.13A.12 Poster Session Sunday, September 8 12:00 - 2:00 pm Highlights of data from Daiichi Sankyo’s ADC portfolio at ESMO 2024 include: Presentation Title Author Abstract Presentation (CEST) NSCLC Datopotamab deruxtecan (Dato-DXd) vs docetaxel in patients with advanced nonsquamous non-small cell lung cancer with brain metastases: results from TROPION-Lung01 E. Pons-Tostivint 1312P Poster Session Saturday, September 14 SCLC Intracranial response in patients with baseline brain metastases and extensive-stage small cell lung cancer treated with ifinatamab deruxtecan (I-DXd) in the IDeate-Lung01 study M. Johnson 1787P Poster Session Saturday, September 14 IDeate-Lung03: a phase 1b/2 study of ifinatamab deruxtecan (I-DXd) plus atezolizumab with or without carboplatin as first line induction or maintenance in patients with extensive stage small cell lung cancer C. Rudin 1812TiP Poster Session Saturday, September 14 BREAST Trastuzumab deruxtecan (T-DXd) in patients with HER2+ advanced/metastatic breast cancer with or without brain metastases: primary results from DESTINY-Breast12 N. Lin LBA18 Proffered Paper Session Friday, September 13 4:00 - 5:30 pm HER2 low and HER2 ultralow status determination in tumors of patients with HR+ mBC in DESTINY-Breast06 G. Viale LBA 21 Mini Oral Session Sunday, September 15 8:30 - 10:00 am Effects of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice on patient-reported outcomes in hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2) low/ultralow metastatic breast cancer: results from DESTINY-Breast06 X. Hu LBA22 Mini Oral Session Sunday, September 15 8:30 - 10:00 am Efficacy, safety and biomarker analysis of ICARUS-BREAST01: a phase 2 study of patritumab deruxtecan (HER3-DXd) in patients with HR+/HER2- advanced breast cancer B. Pistilli 340O Proffered Paper Session Friday, September 13 4:00 - 5:30 pm A multicenter, randomized, double-blind, placebo-controlled study of olanzapine-based triplet antiemetic therapy for prevention of delayed and persistent nausea and vomiting induced by trastuzumab deruxtecan in patients with metastatic breast cancer: ERICA study H. Sakai 1816O Proffered Paper Session Saturday, September 14 2:45 - 4:25 pm Unraveling the mechanisms of action and resistance to trastuzumab deruxtecan (T-DXd): supplementary biomarker analyses from DAISY trial F. Mosele 343MO Mini Oral Session Sunday, September 15 8:30 - 10:00 am Exploratory biomarker analysis of trastuzumab deruxtecan versus treatment of physician’s choice in HER2-low, hormone receptor-positive metastatic breast cancer in DESTINY-Breast04 N. Ueno 432P Poster Session Monday, September 16 Exposure-adjusted incidence rates of adverse events from the TROPION-Breast01 study of datopotamab deruxtecan (Dato-DXd) vs investigator’s choice of chemotherapy in patients with pretreated, inoperable/ metastatic HR+/HER2- breast cancer H. Rugo 431P Poster Session Monday, September 16 Treatment patterns and outcomes in HER2 low, HR+ metastatic breast cancer patients previously treated with endocrine therapy in the United States S. Modi 399P Poster Session Monday, September 16 OTHER SOLID TUMORS Preliminary results from a phase 1, first-in-human study of DS-9606a, a Claudin 6 (CLDN6) directed antibody drug conjugate, in patients with tumor types known to express CLDN6 M. Patel 610O Proffered Paper Session Sunday, September 15 2:45 - 4:15 pm Trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients with advanced/metastatic HER2 positive esophageal, gastric or gastroesophageal junction adenocarcinoma: DESTINY-Gastric03 Y. Janjigian 1401O Proffered Paper Session Saturday, September 14 8:30 - 10:00 am Datopotamab deruxtecan (Dato-DXd) monotherapy in patients with endometrial or ovarian cancer: results from the phase 2 TROPION-PanTumor03 study A. Oaknin 714MO Mini Oral Session Sunday, September 15 2:45 - 4:15 pm HERTHENA-PanTumor01: A global phase 2 trial of HER3-DXd in metastatic solid tumors T. Powles 690TiP Poster Session Saturday, September 14 A phase 1, first-in-human study of DS-1471 in patients with advanced/metastatic solid tumors S. Koganemaru 682TiP Poster Session Saturday, September 14 Claudin-6 expression in primary and recurrent epithelial ovarian cancer: a potential therapeutic target for high-grade serous ovarian cancer D. Shintani 771P Poster Session Saturday, September 14 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. 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 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 .

ADCClinical ResultPhase 1Phase 2Phase 3

25 Jun 2024

·pipelinereview.com

EZHARMIA® Approved in Japan as First Dual EZH1 and EZH2 Inhibitor Therapy for Patients with Peripheral T-Cell Lymphoma

TOKYO, Japan I June 24, 2024 I Daiichi Sankyo’s (TSE: 4568) EZHARMIA® (valemetostat tosilate) has been approved in Japan for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). EZHARMIA is now the first dual inhibitor of EZH1 and EZH2 to be approved for PTCL after receiving SAKIGAKE designation for this indication. PTCL is a group of rare and often aggressive blood cancers, which represent about 10 to 15% of all non-Hodgkin lymphomas (NHL).1 PTCL is more common in Asia, including in Japan, compared to other parts of the world.2 A majority of patients with PTCL experience disease progression following initial treatment with a multi-drug chemotherapy-based regimen and median overall survival following relapse is approximately 5.8 months.1 The approval of EZHARMIA by the Japan Ministry of Health, Labour and Welfare (MHLW) is based on results of the VALENTINE-PTCL01 phase 2 trial, which were presented at the 2023 American Society of Hematology (ASH) Annual Meeting. In VALENTINE-PTCL01, an objective response rate (ORR) of 43.7% (n=52, 95% CI: 34.6-53.1) was observed for EZHARMIA in 119 efficacy evaluable patients with relapsed or refractory PTCL as assessed by CT-based blinded independent central review (BICR). Seventeen complete responses (CRs) and 35 partial responses (PRs) were observed. Responses were seen across a variety of PTCL subtypes including angioimmunoblastic T-cell lymphoma (AITL), PTCL not otherwise specified (PTCL-NOS) and other PTCL subtypes. “This second indication for EZHARMIA in Japan is an important advance for the treatment of relapsed or refractory peripheral T-cell lymphoma, as new and effective treatment options are needed to improve patient outcomes,” said Toshinori Agatsuma, PhD, Executive Officer, Head of R&D Division in Japan, Daiichi Sankyo. “EZHARMIA exemplifies the innovative research being conducted by Daiichi Sankyo aimed at creating new medicines with potential to change the standard of care for patients with cancer.” The safety profile of EZHARMIA in VALENTINE-PTCL01 was consistent with previous clinical trials. Treatment-related adverse events occurred in 106 of 133 patients (79.7%) with the most common including platelet count decrease (44.4%), anemia (27.1%), dysgeusia (24.8%) and neutrophil count decrease (21.1%). About VALENTINE-PTCL01 Trial VALENTINE-PTCL01 is a global, open-label, single-arm, two-cohort phase 2 study evaluating the efficacy and safety of EZHARMIA in patients with relapsed or refractory PTCL and adult T-cell leukemia/lymphoma (ATLL) who received at least one systemic therapy and were ineligible for hematopoietic stem cell transplant at the time of screening. One cohort enrolled patients with PTCL and a second cohort enrolled patients with ATLL. The primary endpoint of VALENTINE-PTCL01 is ORR assessed by CT-based BICR. Secondary endpoints include duration of response, CR, PR, duration of CR and progression-free survival – all assessed by both BICR and investigator assessment – as well as ORR assessed by investigator, overall survival, safety and pharmacokinetics. Exploratory endpoints include PET-CT-based BICR and biomarker mutational status. Responses were evaluated based on Lugano 2014 response criteria. VALENTINE-PTCL01 enrolled 133 patients at multiple sites in Asia, Europe, North America and Oceania. For more information about this study, visit ClinicalTrials.gov. About Peripheral T-Cell Lymphoma PTCL is a group of rare and often aggressive blood cancers, which represent 10 to 15% of all NHLs.1 Approximately 553,000 new cases of NHL were diagnosed worldwide in 2022.3 There are at least 29 recognized subtypes of PTCL, which occur with significant geographic variation.4 PTCL is more common in Asia, including in Japan, compared to other parts of the world.2 Prognosis of PTCL is generally poor, with a five-year overall survival rate of 32% in AITL and PTCL-NOS, and 7% or lower in certain subtypes.5 A majority of patients with PTCL experience disease progression following initial treatment with a multi-drug chemotherapy-based regimen and median overall survival following relapse is approximately 5.8 months.1 Development of more effective medicines for PTCL continues to be an unmet clinical need, particularly in the relapsed or refractory setting.1 About EZH1 and EZH2 The EZH1 (enhancer of zeste homolog 1) and EZH2 (enhancer of zeste homolog 2) enzymes help regulate the expression of genes involved in maintaining healthy hematopoietic stem cells (immature blood cells).6 Both enzymes are recurrently mutated or overexpressed in hematologic malignancies, including T-cell lymphomas, and research shows they contribute to the silencing of tumor suppressor genes and drive oncogenic growth. 7,8 About EZHARMIA EZHARMIA (valemetostat tosilate) is first-in-class dual inhibitor of EZH1 and EZH2 that was discovered by Daiichi Sankyo. EZHARMIA is approved in Japan for the treatment of patients with relapsed or refractory PTCL and for the treatment of patients with relapsed or refractory ATLL. It is an investigational medicine in all countries outside of Japan. About EZHARMIA Clinical Development Program A global clinical development program is underway for EZHARMIA in hematologic and solid cancers. In addition to VALENTINE-PTCL01, EZHARMIA is being evaluated in the VALYM phase 2 trial in patients with relapsed or refractory B-cell lymphomas, which is being conducted under a strategic research collaboration with the LYSA-LYSARC-CALYM group in Europe, and a phase 1b study in combination with DXd antibody drug conjugates ENHERTU® (trastuzumab deruxtecan) and datopotamab deruxtecan (Dato-DXd) in patients with solid cancers. 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 Bellei et al. haematologica. Vol. 103 No. 7 (2018): July 2018 2 Vose JM et al. J Clin Oncol. 2008;26:4124-4130 3 Global Cancer Observatory. Cancer Fact Sheet. February 2024 4 Liang X et al. Medicine 2021; 2021 Apr 2;100(13): e25194. 5 Vose JM et al. J Clin Oncol. 2008;26:4124-4130 6 Honma D et al. Cancer Sci. 2017 Oct; 108(10): 2069–2078 7 Nakagawa M and Kitabayashi I. Cancer Sci. 2018;109:2342–2348 8 Yamagishi et al. Cell Reports. 2019; 29, 2321–2337

Phase 2Clinical ResultDrug ApprovalASHPhase 1

100 Deals associated with Valemetostat Tosilate

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KEGG	Wiki	ATC	Drug Bank
D11551 D16662	-	-	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Adult T-Cell Leukemia-Lymphoma	JP	Daiichi Sankyo Co., Ltd.	26 Sep 2022
Peripheral T-Cell Lymphoma	JP	Daiichi Sankyo Co., Ltd.	26 Sep 2022

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
metastatic non-small cell lung cancer	Phase 2	US	Daiichi Sankyo Co., Ltd.	30 Oct 2024
metastatic non-small cell lung cancer	Phase 2	CN	Daiichi Sankyo Co., Ltd.	30 Oct 2024
metastatic non-small cell lung cancer	Phase 2	JP	Daiichi Sankyo Co., Ltd.	30 Oct 2024
metastatic non-small cell lung cancer	Phase 2	AR	Daiichi Sankyo Co., Ltd.	30 Oct 2024
metastatic non-small cell lung cancer	Phase 2	BR	Daiichi Sankyo Co., Ltd.	30 Oct 2024
metastatic non-small cell lung cancer	Phase 2	KR	Daiichi Sankyo Co., Ltd.	30 Oct 2024
Follicular Lymphoma	Phase 2	US	Daiichi Sankyo Co., Ltd.	19 May 2023
B-Cell Lymphoma	Phase 2	EU	Daiichi Sankyo Co., Ltd.	30 Jan 2022
B-cell lymphoma refractory	Phase 2	BE	Daiichi Sankyo Co., Ltd.	11 Jun 2021
B-cell lymphoma refractory	Phase 2	FR	Daiichi Sankyo Co., Ltd.	11 Jun 2021

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04703192 (VALENTINE-PTCL01, Pubmed \| Lancet Oncol)	Phase 2	Peripheral T-Cell Lymphoma	-	Valemetostat tosylate (valemetostat) 200 mg per day	cmgacvlgdv(zivrwvowzp) = dudaevelfr wkcnryhvuv (vmicsbzehu, 35 - 53)	Positive	01 Dec 2024
NCT02732275 (DS3201-A-J101, SOHO2024)	Phase 1	Non-Hodgkin Lymphoma EZH2 mutation	90	Valemetostat tosylate 150-300 mg/day	ddigbdxdbt(gkgdxqqnvp) = All experienced ≥1 treatment-emergent adverse event (TEAE); 78 (87%) had ≥1 treatment-related adverse event adjdeqsfbf (xumiaynljw ) View more	Positive	04 Sep 2024
NCT02732275 (DS3201-A-J101, SOHO2024)	Phase 1	Non-Hodgkin Lymphoma EZH2 mutation	90	Valemetostat tosylate 200 mg/day		Positive	04 Sep 2024
NCT04703192 (VALENTINE-PTCL01, SOHO2024)	Phase 2	Peripheral T-Cell Lymphoma	133	Valemetostat 200 mg	oyikxyzcvj(rtzkaomskk) = Thrombocytopenia was the most common any grade/Grade ≥3 TEAE (49.6%/23.3%) eflfcsmift (wdbrzjheed ) View more	Positive	04 Sep 2024
NCT04703192 (VALENTINE-PTCL01, CTgov)	Phase 2	Adult T-Cell Leukemia-Lymphoma \| Peripheral T-Cell Lymphoma \| Adult T-cell lymphoma/leukaemia refractory	155	Valemetostat Tosylate	wmvyvsmbwh(akpagsrqdy) = jilfyenemf ssszaldzlh (ddcpfucodo, ohxirdhgoh - zcnmlvhavf) View more	-	22 Jul 2024
NCT04703192 (VALENTINE-PTCL01, EHA2024) Manual	Phase 2	Peripheral T-Cell Lymphoma	119	Valemetostat tosylate 200 mg/day (pts with 1 prior LOT)	jtjnnwciih(gorunbrrki) = bpapejwsbp zehvpmwqol (pzlokwggmv, 35.5 - 69.6)	Positive	14 May 2024
NCT04703192 (VALENTINE-PTCL01, EHA2024) Manual	Phase 2	Peripheral T-Cell Lymphoma	119	Valemetostat tosylate 200 mg/day (pts with 2 prior LOT)	jtjnnwciih(gorunbrrki) = lwpmdacwpu zehvpmwqol (pzlokwggmv, 28.3 - 65.7)	Positive	14 May 2024
NCT02732275 (DS3201-A-J101, EHA2024) Manual	Phase 1	Non-Hodgkin Lymphoma EZH2 mutation	90	valemetostat tosylate 150-300 mg/d	bqxatstjux(gokoxerqgd) = jwvfbmvuly huwdmzdikh (bftefflwci ) View more	Positive	14 May 2024
NCT02732275 (DS3201-A-J101, EHA2024) Manual	Phase 1	Non-Hodgkin Lymphoma EZH2 mutation	90	valemetostat (ATLL)	(ttsblzgrex) = vwytikoghl yuwmbvfbkr (alkdvmjavh, 1.4 - 38.7) View more	Positive	14 May 2024
NCT03110354 (CTgov)	Phase 1	Acute Myeloid Leukemia \| Acute Lymphoblastic Leukemia	28	DS-3201b (DS-3201b 150 mg)	surdfamcoi(ieqpeqfigh) = ptsccnfrxx chpitpslwr (mkmushhgvg, jrppzgngyo - msqpdtgmrg) View more	-	30 Jan 2024
NCT03110354 (CTgov)	Phase 1	Acute Myeloid Leukemia \| Acute Lymphoblastic Leukemia	28	DS-3201b (DS-3201b 250 mg)	surdfamcoi(ieqpeqfigh) = lmkorxhbvl chpitpslwr (mkmushhgvg, ggvlfjktnm - qayicplzde) View more	-	30 Jan 2024
VALENTINE-PTCL01 (ASH2023)	Phase 2	Peripheral T-Cell Lymphoma	133	Valemetostat 200 mg/day	vmnoxsbhxr(lvuhyzqsny) = rwvjobuohe vtfhetfesl (pgaqyacpwn, 34.6 - 53.1) View more	-	09 Dec 2023
ASH2023	Phase 1	Peripheral T-Cell Lymphoma	71	Valemetostat	bdzwyhtseq(eflgcxcmop) = qcjlgapffd khihloitvz (xrbjmecmmi ) View more	-	09 Dec 2023
ASH2023	Phase 1	B-cell lymphoma refractory	19	Valemetostat	lsjdzzzuyj(lnntcsskfm) = The most common TEAEs (any grade) were decreased platelet count (64%), dysgeusia (50%), anemia (43%), decreased neutrophil count (34%), and alopecia (33%) cowjnzxbjo (tnfnkgawqb ) View more	-	09 Dec 2023

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Understand key drug designations in just a few clicks with Synapse.

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Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis