The main purpose of this research study is to find out if de-escalation of chemotherapy before surgery followed by a selective escalation of adjuvant targeted therapies are efficacious and tolerable in early-stage HER2 positive breast cancer.

Start Date11 Aug 2025

Sponsor / Collaborator

University of Rochester

NCT06348134 / Not yet recruitingPhase 2IIT

Assessing the Efficacy and Safety of Optimal Neoadjuvant to Adjuvant Anti-HER2- Based Therapy in Nigerian Women With HER2+ Breast Cancer

Doctors leading this study would like to learn about providing cancer treatment/therapies to Nigerian women with breast cancer based on their human epidermal growth factor receptor 2 (HER2) status. This study will focus on the efficacy and safety of anti-HER2 cancer treatment before and after surgery.

Start Date01 Jan 2025

Sponsor / Collaborator

The University of Chicago

NCT06439693 / Not yet recruitingPhase 2IIT

A Single-Arm, Phase II Study of Sequential Therapy With Curative Intent in de Novo HER2+ Metastatic Breast Cancer: The SAPPHO Study:

The purpose of this study is to test the safety and effectiveness of a sequence of drugs (a Taxane plus Trastuzumab plus Pertuzumab followed by Trastuzumab Deruxtecan, followed by Tucatinib plus Ado-Trastuzumab Emtansine (T-DM1), followed by Trastuzumab plus Pertuzumab plus Tucatinib) in HER2+ Breast Cancer. The study will help investigators understand whether first intensifying therapy for a specific period and then stopping treatment is safe and effective for participants.
The names of the study drugs involved in this study are:
Paclitaxel (a type of anti-microtubule agent)
Docetaxel (a type of anti-microtubule agent)
Nab-Paclitaxel (a type of anti-microtubule agent)
Trastuzumab (a type of IgG1 kappa monoclonal antibody)
Pertuzumab (a type of monoclonal antibody)
Trastuzumab Deruxtecan (a type of HER2-directed antibody drug conjugate)
Tucatinib (Tyrosine Kinase HER2 Inhibitor)
Ado-trastuzumab emtansine or T-DM1 (a type of HER2-targeted antibody-drug conjugate)

Start Date01 Nov 2024

Sponsor / Collaborator

Dana-Farber Cancer Institute, Inc.

[+1]

100 Clinical Results associated with ADO-Trastuzumab Emtansine

100 Translational Medicine associated with ADO-Trastuzumab Emtansine

100 Patents (Medical) associated with ADO-Trastuzumab Emtansine

1,323

Literatures (Medical) associated with ADO-Trastuzumab Emtansine

01 Jan 2025·BIOORGANIC & MEDICINAL CHEMISTRY

The journey of antibody-drug conjugates for revolutionizing cancer therapy: A review

Review

Author: Akhtar, Muhammad Tayyab ; ul Haq, Ikram ; Fatima, Taseer ; Akram, Fatima ; Ali, Amna Murrawat ; Shabbir, Ifrah ; Ul Haq, Ikram

Antibody-drug conjugates (ADCs) represent a powerful class of targeted cancer therapies that harness the specificity of monoclonal antibodies to deliver cytotoxic payloads directly to tumor cells, minimizing off-target effects. This review explores the advancements in ADC technologies, focusing on advancing next-generation ADCs with novel payloads, conjugation strategies, and enhanced pharmacokinetic profiles. In particular, we highlight innovative payloads, including microtubule inhibitors, spliceosome modulators, and RNA polymerase inhibitors, that offer new mechanisms of cytotoxicity beyond traditional apoptosis induction. Additionally, the introduction of sophisticated conjugation techniques, such as site-specific conjugation using engineered cysteines, enzymatic methods, and integration of non-natural amino acids, has greatly improved the homogeneity, efficacy, and safety of ADCs. Furthermore, the review delves into the mechanistic insights into ADC action, detailing the intracellular pathways that facilitate drug release and cell death, and discussing the significance of bioconjugation methods in optimizing drug-antibody ratios (DARs). The establishment of comprehensive databases like ADCdb, which catalog vital pharmacological and biological data for ADCs, is also explored as a critical resource for advancing ADC research and clinical application. Finally, the clinical landscape of ADCs is examined, with a focus on the evolution of FDA-approved ADCs, such as Gemtuzumab Ozogamicin and Trastuzumab Emtansine, as well as emerging candidates in ongoing trials. As ADCs continue to evolve, their potential to revolutionize cancer therapy remains immense, offering new hope for more effective and personalized treatment options. ADCs also offer a significant advancement in targeted cancer therapy by merging the specificity of monoclonal antibodies with cytotoxic potency of chemotherapeutic agents. Hence, this dual mechanism intensifies tumor selectivity while minimizing systemic toxicity, paving the way for more effective and safer cancer treatments.

05 Dec 2024·NEURO-ONCOLOGY

Final outcome analysis from the phase II TUXEDO-1 trial of trastuzumab-deruxtecan in HER2-positive breast cancer patients with active brain metastases

Article

Author: Roider-Schur, Sophie ; Bago-Horvath, Zsuzsanna ; Widhalm, Georg ; Berghoff, Anna Sophie ; Furtner, Julia ; Forstner, Heidrun ; Rottenmanner, Beate ; Szekeres, Thomas ; Gruenberger, Birgit ; Ilhan-Mutlu, Aysegül ; Starzer, Angelika Martina ; Berchtold, Luzia ; Marhold, Maximilian ; Bergen, Elisabeth Sophie ; Singer, Christian ; Aretin, Marie-Bernadette ; Minichsdorfer, Christoph ; Oehler, Leopold ; Fuereder, Thorsten ; Bartsch, Rupert ; Weltermann, Ansgar ; Mair, Maximilian Johannes ; Pfeiler, Georg ; Preusser, Matthias ; Dieckmann, Karin ; Haslacher, Helmuth

Abstract:

Background:

Brain metastases (BM) are a devastating complication of HER2-positive metastatic breast cancer (BC) and treatment strategies providing optimized local and systemic disease control are urgently required. The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) over trastuzumab emtansine but data regarding intracranial activity is limited. In the primary outcome analysis of TUXEDO-1, a high intracranial response rate (RR) was reported with T-DXd. Here, we report the final PFS and OS results.

Patients and Methods:

TUXEDO-1 accrued adult patients with HER2-positive BC and active BM (newly diagnosed or progressing) without indication for immediate local therapy. The primary endpoint was intracranial RR; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analyzed in the per-protocol population.

Results:

At 26.5 months median follow-up, median PFS was 21 months (95% CI: 13.3–n.r.) and median OS was not reached (95% CI: 22.2–n.r.). With longer follow-ups, no new safety signals were observed. The most common grade 3 adverse event was fatigue (20%). Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL was maintained over the treatment period.

Conclusions:

T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive BC BM in line with results from the pivotal trials. These results support the concept of antibody-drug-conjugates as systemic therapy for active BM.

04 Dec 2024·Future Oncology

Cardiac toxicity of HER-2 targeting antibody–drug conjugates: overview and clinical implications

Review

Author: Mohanna, Rami ; Kourie, Hampig-Raphael ; Noujaim, Charbel ; Farhat, Mohamad ; Rita Hachem, Maria Catherine ; Zalaquett, Ziad ; Assi, Ahmad

Antibody-drug conjugates (ADCs) have recently emerged as a promising therapeutic option that combine the specificity of monoclonal antibodies and the cytotoxic effect of chemotherapy. With numerous ADCs approved and on the market, a particular concern of ADCs that target HER-2 has been their cardiac side effects, in view of the crucial role of HER-2 in cardiac development and physiology. While rarely toxic and generally safe, numerous publications have outlined the consistent association of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) with the development of cardiac toxicity. Despite not being clinically relevant in most cases, cardiac baseline evaluation, monitoring and early detection of cardiac adverse events remain pivotal with HER-2 targeting ADCs. This review aims to summarize and better characterize the complete cardiac toxicity profile of HER-2 ADCs, with the goal of improving clinical understanding of this adverse event, leading to better recognition, monitoring and management.

120

News (Medical) associated with ADO-Trastuzumab Emtansine

18 Dec 2024

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Valink Therapeutics Appoints Biopharmaceutical Veteran Martin D. Williams as Chair of the Board of Directors and Names Scientific Advisory Board

BOSTON--( BUSINESS WIRE )--Valink Therapeutics, a biopharmaceutical company focused on discovering and developing innovative bispecific antibody-drug conjugates (bsADCs) to transform the treatment of cancer and other diseases, has appointed Martin D. Williams as Chair of its Board of Directors. The company also named its Scientific Advisory Board, which assembles experts in the discovery, development, manufacture and commercialization of ADCs and bispecific therapeutics. “ We are thrilled to welcome Martin, whose expertise in strategy, development and partnering, and track record of leading multiple U.S. biopharmaceutical companies, will be instrumental to the next stages of Valink. He brings deep experience advancing a wide range of therapeutics from early development through regulatory approval and commercialization and developing industry partnerships that move promising medicines closer to patients. Martin’s career journey, which began in the UK before his move to the U.S. over 30 years ago, mirrors Valink’s roots as a University of Oxford spinout based in the U.S., with a strong UK presence,” said Arne Scheu, DPhil, Co-founder and Chief Executive Officer of Valink. “ Furthermore, I am excited to announce our Scientific Advisory Board, which brings together a distinguished group of advisors who have been at the forefront of ADC and bispecific innovation and development.” Mr. Williams brings to Valink more than 35 years of experience in the global biopharmaceutical business, having closed more than $5 billion worth of corporate transactions, including numerous partnerships, M&A, and public and private financings. He recently served as Chief Executive Officer of Caraway Therapeutics, a venture-backed company developing therapeutics to modulate lysosomal function for neurodegenerative and rare diseases, through the company’s acquisition by Merck & Co. at the end of 2023. Previously, he was President and Chief Executive Officer of Tokai Pharmaceuticals, a clinical-stage oncology company; Chief Business Officer at Dicerna Pharmaceuticals, a leading RNAi company with programs in oncology; and Chief Business Officer and Senior Vice President for commercial and business development at Synta Pharmaceuticals, a clinical-stage public company focused on oncology and inflammation. Earlier in his career, he held various leadership positions and directed the development, commercialization and launch of several flagship brands for GSK, Hoffmann-La Roche and Lederle/Wyeth (now Pfizer), including GSK’s blockbusters Zantac® and Zofran®; Hoffmann La-Roche’s Xenical®; and Lederle/Wyeth’s global anti-infective portfolio, including Zosyn®/Tazocin®. He holds an MBA from Harvard Business School and an MS from the University of Manchester, UK. “ Valink has developed a compelling approach to realizing the unmet potential of ADCs to improve outcomes for patients with cancer and other diseases, which has been restricted by dose-limiting toxicities and the range of suitable targets. Their technology addresses a significant challenge to ADC innovation by enabling rapid and cost-effective generation and screening of bispecific ADCs, unlocking a vast range of target synergy and potentially bringing previously undruggable space within reach,” said Mr. Williams. “ I am excited to work closely with the Valink executive team and Board as the company builds on its discoveries and pursues its clinical aspirations.” Valink also announced the formation of its Scientific Advisory Board, initially consisting of: Sonia Quaratino, MD, PhD is Executive Vice President and Chief Medical Officer at Innate Pharma, a clinical-stage biotech utilizing monoclonal antibodies, multi-specific NK cell engagers and ADCs to develop immunotherapies for cancer. Her career spans over 25 years in basic research, clinical development and translational medicine across academia, biotech and global pharmaceuticals. She has held numerous leadership positions, including serving as CMO at Kymab (until its acquisition by Sanofi) and Georgiamune Inc, and was Professor of Immunology at the University of Southampton. Marc Damelin, PhD is Chief Scientific Officer at Alphina Therapeutics and an expert in oncology drug discovery and development. Previously he served as VP and Head of Biology at Mersana Therapeutics, a clinical-stage biotech developing ADCs to treat cancer. Prior to that he worked for a decade in ADC discovery and development in Pfizer's Oncology Research Unit. Robert Lutz, PhD , Chief Scientific Officer at leading ADC company Iksuda Therapeutics, is a recognized expert in ADC discovery and development. As VP of Translational R&D at ImmunoGen, he was responsible for bringing eight ADC product candidates into development and was the research lead for Kadcyla®, the first ADC to be approved for solid tumor indications. Antoine Awad , Principal Executive Officer of Synlogic, has extensive experience in CMC, bispecific drug development and partnerships. Prior to Synlogic, he held leadership positions at various biotechs, including Merrimack Pharmaceuticals, where he led CMC development, manufacturing and approval of ONIVYDE® for treatment of advanced pancreatic cancer and transitioned to Ipsen Bioscience to lead global commercial manufacturing of ONIVYDE®. Mihriban Tuna, PhD is Chief Executive Officer of Immutrin and Entrepreneur-in-Residence at Cambridge Innovation Capital, a leading UK-based venture company focused on deep tech and life sciences. She previously served as Chief Scientific Officer at Adaptate Biotherapeutics (acquired by Takeda) and SVP, Drug Discovery at F-star Therapeutics, and was an early employee at Domantis Ltd. (acquired by GSK). Alexey A. Lugovskoy, PhD is President and Chief Executive Officer of Diagonal Therapeutics, Entrepreneur-in-Residence at Atlas Ventures and Associate Editor of mAbs . He formerly served as Chief Operating Officer at Dragonfly, Chief Development Officer at Morphic, Vice President of Therapeutics at Merrimack Pharmaceuticals and Associate Director of Drug Discovery at Biogen. He joined Valink’s Board of Directors in 2023, and this additional appointment highlights a close collaboration between the Scientific Advisory Board, Board of Directors and leadership team. About Valink Therapeutics Valink Therapeutics Inc. is a biopharmaceutical company focused on the discovery and development of first-in-class bispecific antibody-drug conjugates (bsADCs) to transform the treatment of cancer and other diseases. Valink’s technology platform utilizes a modular assembly approach to rapidly generate bsADCs with therapeutic potential, testing drugs at unparalleled scale and speed to improve on the payload delivery and selectivity of conventional ADCs. The company is based in Boston, Massachusetts and has research and development operations in London, UK. For more information, visit the company’s website at www.valinktx.com or contact the company at connect@valinktx.com .

Executive ChangeADCAcquisitionDrug Approval

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

25 Nov 2024

·www.prnewswire.com

Roche receives FDA approval for first companion diagnostic to identify patients with biliary tract cancer eligible for HER2-targeted treatment with ZIIHERA

The PATHWAY HER2 (4B5) test helps to identify patients with previously-treated, unresectable or metastatic HER2-positive biliary tract cancer (BTC) who may be eligible for treatment with ZIIHERA. There are currently very few options for BTC patients as most cases are at an advanced stage at the time of diagnosis. This approval represents a new indication for Roche's existing PATHWAY HER2 (4B5) test and expands its clinical utility by broadening the scope of patients who are eligible for HER2-targeted therapies. TUCSON, Ariz., Nov. 25, 2024 /PRNewswire/ -- Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today the U.S. Food and Drug Administration (FDA) approval of a label expansion into biliary tract cancer (BTC) for the PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody* test. This test is now the first and only FDA-approved companion diagnostic to aid in the assessment of HER2-positive status to identify BTC patients who are eligible for treatment with Jazz Pharmaceuticals' ZIIHERA® (zanidatamab-hrii). Continue Reading PATHWAY HER2 (4B5) assay for biliary tract cancer HER2 is a receptor protein expressed in a variety of cancers and serves as a predictive biomarker to help determine if a patient will respond to HER2-targeted therapy.1 No approved and validated HER2 test existed to identify eligible BTC patients until the approval of this expanded label for the PATHWAY HER2 (4B5) test. "This test is a step forward in furthering access to personalised medicine," said Jill German, Head of Pathology Lab at Roche Diagnostics. "The prognosis for patients diagnosed with BTC is poor, as very few treatment options exist. Now, these patients have access to the first standardised test that could make them eligible for targeted therapy, potentially improving clinical outcomes." ZIIHERA is the first FDA-approved treatment for adults with previously-treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer. BTC accounts for 3% of all gastrointestinal cancers in the US.2,3 Prognosis is poor because of a lack of adequate early detection tools, challenging anatomical access, aggressive tumour biology, and only modest benefit from systemic treatments.4 With most cases diagnosed at an advanced stage,5 the five-year overall survival rate for all BTC cases is 19% for disease that is localised to the original tumour site, and just 3% for cancer that has spread to other areas.6 About the PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody The PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody delivers timely, clear and reliable results, enabling therapeutic decisions that can lead to better outcomes for patients. Already indicated as an aid to identify breast cancer patients eligible for HER2-targeted treatment with Herceptin®, KADCYLA®, or ENHERTU®,7 the test is used in combination with the fully automated VENTANA® BenchMark slide staining instrument. The introduction of the new indication for BTC represents a significant expansion of the test's clinical utility. The assay forms an important part of Roche's comprehensive gastrointestinal cancer solutions portfolio, which is aimed at driving diagnostic certainty for life-changing decisions in cancer care. The assay standardises all immunohistochemistry (IHC) processes from baking through staining, and reduces the possibility of human error.8 It also minimises inherent variability resulting from individual reagent dilution and other processes found in manual and semi-automated IHC methods. The Roche HER2 (4B5) clone achieves consistently high proficiency assessment scores compared to other clones9 and demonstrates high concordance with HER2 FISH,10,11 empowering laboratories to employ the most widely adopted and reliable HER2 IHC primary antibody. For more information about the portfolio, please visit the Roche Diagnostics Pathology Lab companion diagnostics page. About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world's largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For over 125 years, sustainability has been an integral part of Roche's business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit . References[1] Yoon, J., Oh, DY. Nat Rev Clin Oncol 21, 675–700 (2024) [2] Harding, J. et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZONBTC-01): a multicentre, single-arm, phase 2b study. Lancet Oncol 2023; 24: 772–82. [3] Scott, A. et al. Precision Medicine in Biliary Tract Cancer. J Clin Oncol 2022 40:2716-2734. [4] Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Biliary Tract Cancer V.2.2024. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. [5] Valle JW, Kelley RK, Nervi B, Oh D-Y, Zhu AX. Biliary tract cancer. Lancet 2021; 397: 428–44. [6] Nakanuma Y, Kakuda Y: Pathologic classification of cholangiocarcinoma: New concepts. Best Pract Res Clin Gastroenterol 29:277-293, 2015 [7] PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody, US Package Insert (D197603 Rev 1). 2024. [8] VENTANA HER2 (4B5) Rabbit Monoclonal Primary Antibody RxDx Package Insert, 2024. [9] NordiQC Assessments [10] Mayr D, et al. Comprehensive immunohistochemical analysis of Her-2/neu oncoprotein overexpression in breast cancer: HercepTest™ (Dako) for manual testing and Her-2/neuTest 4B5 (VENTANA) for VENTANA BenchMark automatic staining system with correlation to results of BenchMark automatic staining system with correlation to results of fluorescence in situ hybridization (FISH). Virchows Archiv. 2009; 454(3):241–248. [11] Brügmann A, Lelkaitis G, Nielsen S, et al. Testing HER2 in breast cancer: a comparative study on BRISH, FISH, and IHC. Appl Immunohistochem Mol Morphol. 2011;19(3):203-211. Roche Media Relations Jo Lynn Garing Phone: +1 317-363-7286 Email: [email protected] SOURCE Roche WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Drug ApprovalPhase 2

100 Deals associated with ADO-Trastuzumab Emtansine

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KEGG	Wiki	ATC	Drug Bank
-	ADO-Trastuzumab Emtansine	L01XC14	DB05773

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Breast Cancer	EU	Roche Registration GmbH	15 Nov 2013
Breast Cancer	IS	Roche Registration GmbH	15 Nov 2013
Breast Cancer	LI	Roche Registration GmbH	15 Nov 2013
Breast Cancer	NO	Roche Registration GmbH	15 Nov 2013
Metastatic breast cancer	EU	Roche Registration GmbH	15 Nov 2013
Metastatic breast cancer	IS	Roche Registration GmbH	15 Nov 2013
Metastatic breast cancer	LI	Roche Registration GmbH	15 Nov 2013
Metastatic breast cancer	NO	Roche Registration GmbH	15 Nov 2013
HER2 Positive Breast Cancer	US	Genentech, Inc.	22 Feb 2013

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Gastroesophageal junction adenocarcinoma	Phase 3	US	Hoffmann-La Roche, Inc.	03 Sep 2012
Gastroesophageal junction adenocarcinoma	Phase 3	CN	Hoffmann-La Roche, Inc.	03 Sep 2012
Gastroesophageal junction adenocarcinoma	Phase 3	JP	Hoffmann-La Roche, Inc.	03 Sep 2012
Gastroesophageal junction adenocarcinoma	Phase 3	AR	Hoffmann-La Roche, Inc.	03 Sep 2012
Gastroesophageal junction adenocarcinoma	Phase 3	BE	Hoffmann-La Roche, Inc.	03 Sep 2012
Gastroesophageal junction adenocarcinoma	Phase 3	BR	Hoffmann-La Roche, Inc.	03 Sep 2012
Gastroesophageal junction adenocarcinoma	Phase 3	CA	Hoffmann-La Roche, Inc.	03 Sep 2012
Gastroesophageal junction adenocarcinoma	Phase 3	CZ	Hoffmann-La Roche, Inc.	03 Sep 2012
Gastroesophageal junction adenocarcinoma	Phase 3	FI	Hoffmann-La Roche, Inc.	03 Sep 2012
Gastroesophageal junction adenocarcinoma	Phase 3	FR	Hoffmann-La Roche, Inc.	03 Sep 2012

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04197687 (ASCO2024) Manual	Phase 2	HER2 Positive Breast Cancer Neoadjuvant	20	H2NVAC + T-DM1	ewpftyaxdi(jvgvvfzjuh) = gbhxcthssj xngjzjmqkx (axroeavfoe ) View more	Positive	24 May 2024
ASCO2024	Not Applicable	Adjuvant	116	Biosimilar TDM1	bidsepffwu(sfbqvlcsjt) = Common adverse effects were fatigue urmycjfuox (orguacfbwb ) View more	Positive	24 May 2024
ASCO2024	Not Applicable	Metastatic human epidermal growth factor 2 positive carcinoma of breast HER2 2+	172	T-DM1	oaxhelylwo(osyyefbbth) = hexiqrjkhh bcflsebcgh (rkzosbrnax, 3.9 - 6.3) View more	Negative	24 May 2024
JPRN-UMIN000030783 (JCOG1607 HERB TEA, ASCO2024)	Phase 3	Advanced HER2-Positive Breast Carcinoma First line	148	Trastuzumab emtansine (T-DM1)	kahcgevbjb(ctinsgyfss) = djvwhkbwui plkowffife (ozssqczfqn, 0.310 - 1.808)	Negative	24 May 2024
NCT02568839 (PREDIX HER2, ESMO_BC2024)	Phase 2	HER2 Positive Breast Cancer Neoadjuvant Ki67 \| age \| CCL3 ... View more	90	Trastuzumab emtansine (T-DM1)	nstxzeioko(tgatukbucm) = grjryidjkv gddetgffcj (moauvgpnkw ) View more	Positive	14 May 2024
NCT02568839 (PREDIX HER2, ESMO_BC2024)	Phase 2		90	Placebo	nstxzeioko(tgatukbucm) = lxqohbjnkq gddetgffcj (moauvgpnkw ) View more	Positive	14 May 2024
NCT02236000 (NSABP FB-10, Pubmed) Manual	Phase 1/2	HER2 Positive Breast Cancer Second line HER2 Positive	49	T-DM1 + neratinib	qafhxscouw(sjupgukktp) = zheklhmwon thvruvcitm (qwdgfvniet ) View more	Positive	22 Apr 2024
NCT04589845 (TAPISTRY, AACR2024) Manual	Phase 2	HER2 Positive Solid Tumors HER2	35	Trastuzumab emtansine	efqzfetdao(cbrpomdacl) = ybrcjqppal heogatmclj (dfwykbezsj, 4.8 - 30.3) View more	Negative	05 Apr 2024
ESMO_ASIA2023	Not Applicable	Metastatic human epidermal growth factor 2 positive carcinoma of breast HER2-positive	30	T-DM1 biosimilar	iekxhyotgw(qejylwgnvz) = lexibzospg zagyhegroy (bxzfdlvhch, 13.46 - 17.17) View more	Positive	02 Dec 2023
ESMO2023	Not Applicable	Breast Cancer HER2 overexpression	-	Patients treated with Pertuzumab	qufhvnweyo(axhxqbotiq) = kntpdplgws ivrysmtnaa (chlcchaqlc, [60.6 - 63.1])	-	21 Oct 2023
ESMO2023	Not Applicable	Breast Cancer HER2 overexpression	-	Patients treated with T-DM1 after Pertuzumab	nyacnnuhpw(lrlmuodxia) = zibrpoakmv zhfgxmdvip (elcouzolyl, [34.6 - 39.4]) View more	-	21 Oct 2023
NCT03975647 (HER2CLIMB-02, Corporate Publications) Manual	Phase 3	HER2 Positive Breast Cancer HER2 Positive	-	TUKYSA+Kadcyla	rxbujaarvr(nxqvvbjfsd) = met its primary endpoint of progression-free survival (PFS) kgwwarjcrv (gpcfbcxmpq ) Met	Positive	16 Aug 2023

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