Phase 1 Study of Trastuzumab Deruxtecan (DS-8201a) in Combination With Azenosertib (ZN-c3) in HER2-Expressing/Amplified Cyclin E-Amplified Gastric/Gastroesophageal Junction Cancer and Other Solid Tumors With HER2 Expression

This phase I trial tests the safety, side effects, and best dose of azenosertib in combination with trastuzumab deruxtecan in treating patients with HER2-positive and cyclin E amplified gastric or gastroesophageal junction cancer and other HER2-positive solid tumors that have spread to nearby tissue or lymph nodes (locally advanced), that have spread from where it first started (primary site) to other places in the body (metastatic), or that cannot be removed by surgery (unresectable). Azenosertib is in a class of medications called kinase inhibitors. It inhibits a protein called Wee1. Inhibition of the Wee1 protein can make tumor cells more vulnerable to chemotherapy drugs, leading to tumor cell death. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Giving azenosertib in combination with trastuzumab deruxtecan may be safe, tolerable, and/or more effective in treating patients with locally advanced, metastatic, or unresectable HER2-positive gastric, gastroesophageal junction, or other solid tumors, compared to just trastuzumab deruxtecan alone.

Start Date07 Jul 2025

Sponsor / Collaborator

National Cancer Institute

NCT06603974 / Not yet recruitingNot ApplicableIIT

An Exploratory Study of Benmelstobart in Combination with Antiangiogenesis Drugs and Neoadjuvant Chemotherapy for Locally Progressive Gastric Cancer / Gastroesophageal Junction Carcinoma

The goal of this clinical trial is to evaluate the major pathological response (MPR) rate of locally advanced gastric cancer / gastroesophageal junction cancer treated with bemosumab combined with antiangiogenic drugs and neoadjuvant chemotherapy.
Researchers will use drug Benmelstobart in combination with antiangiogenesis drugs and newadjuvant chemotherapy to see if the drug works to treat locally advanced gastric cancer / gastroesophageal junction cancer.
Participants will:injection drug Benmelstobart，On the first day of each cycle, 3 weeks (21 days) were a treatment cycle.

Start Date16 Oct 2024

Sponsor / Collaborator

Xijing Hospital

NCT06396143 / RecruitingNot ApplicableIIT

Research on Intelligent Screening and Decision-making for Neoadjuvant Therapy in Locally Advanced Gastric Cancer Based on Multi-omics Integration

In this study, investigators utilize a radiopathomics integrated Artificial Intelligence (AI) supportive system to predict tumor response to neoadjuvant chemoradiotherapy (nCRT) before its administration for patients with locally advanced gastric cancer (LAGC). By the system, the postoperative tumor regression grade (TRG) of the participants will be identified based on the radiopathomics features extracted from the pre-nCRT Enhanced CT and biopsy images. The ability to predict TRG will be validated in this multicenter, prospective clinical study.

Start Date01 Jul 2024

Sponsor / Collaborator

Zhejiang University

100 Clinical Results associated with Locally Advanced Gastric Carcinoma

100 Translational Medicine associated with Locally Advanced Gastric Carcinoma

0 Patents (Medical) associated with Locally Advanced Gastric Carcinoma

557

Literatures (Medical) associated with Locally Advanced Gastric Carcinoma

01 Nov 2024·Biotechnology and Genetic Engineering Reviews

Preliminary report on the short-term efficacy and safety of SAPO-S1 therapy for locally advanced gastric cancer with a deep learning perspective

Article

Author: Han, Guoda ; Zhang, Lei ; Liu, Xu ; Zhang, Xiaoling ; Wei, Xiaonan ; Lin, Yecheng ; Xie, Yanchao

The neoadjuvant therapeutic effects of various chemotherapeutic drugs on gastric cancer have reached the corresponding plateau. Whether the combination of sindilizumab and albumin-bound paclitaxel+oxaliplatin+S-1 chemotherapy (SAPO-S1 therapy) regimen can bring better efficacy and observe the incidence of adverse reactions in the neoadjuvant treatment of Gastric Cancer (GC) may be the direction of our research. This study aimed to evaluate the efficacy of S1 chemotherapy regimen combined with multiple chemotherapy drugs sindilizumab (PD-1 inhibitor), albumin-bound paclitaxel and oxaliplatin) for neoadjuvant therapy in locally advanced Gastric Cancer (LA-GC). The patients were given 4 cycles of sindilizumab combined with albumin paclitaxel+oxaliplatin+S-1 chemotherapy (SAPO-S1) before surgery. The R0 resection rate, surgical complications, pathologic complete response, complete pathologic response (pCR) the main pathological response rates (residual tumor cells≤10%, major pathological response) were observed. MPR and postoperative pathological tumor regression grade (TRG), using the response evaluation criteria in solid tumors (RECIST1.1) to evaluate the efficacy of new adjuvant therapy and record the short-term adverse events (adverse event, AE) of patients after medication to evaluate safety. The overall response rate (ORR) was achieved to 53.3% and disease control rate (DCR) was achieved in 28 patients (93.3%), and the descending phase was achieved in 17 patients (56.7%). The tumor resolution grades of TRG 0, TRG 1, TRG 2 and TRG 3 were 16.7%, 13.3%, 43.3% and 16.7%, respectively. The pCR rate was 16.7%, the MPR rate was 30.0%, and the R0 resection rate was 90.0%. In addition, SAPO-S1 therapy has fewer side effects. Overall, SAPO-S1 therapy has a good therapeutic effect and safety in LA-GC.

01 Oct 2024·Surgery Today

Prognostic significance of a pathological response in metastatic lymph nodes of patients with gastric cancer who underwent neoadjuvant chemotherapy followed by surgery

Article

Author: Huo, Junjie ; Chen, Fengju ; Xian, Jia

PURPOSETo grade the pathological response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC) and investigate its prognostic significance.METHODSThis retrospective study included 196 patients who underwent NAC, followed by radical gastrectomy for LAGC between January 2010 and October 2019. Pathological responses were evaluated based on the proportion of residual tumor cells within the tumor area in the primary tumor (PT) and LNs and included the following categories: 1a (0%), 1b (< 10%), 2 (10-50%), and 3 (> 50%).RESULTSAmong 166 patients with clinically node-positive disease, 38/27/39/62 were classified as having LN regression grade (LRG) 1a/1b/2/3, respectively. Compared to LN non-responders (LRG 2 or 3), LN responders (LRG 1a or 1b) had significantly higher 5-year overall survival (72.5% vs. 19.0%, P < 0.001) and recurrence-free survival rates (67.8% vs. 22.2%, P < 0.001), irrespective of PT response. Furthermore, a multivariate analysis revealed that the LN response was an independent risk factor for the overall survival (hazard ratio [HR] 0.417, 95% confidence interval [CI] 0.181-0.962, P = 0.040) and recurrence-free survival (HR 0.490, 95% CI 0.242-0.991, P = 0.047), but not the PT response (P > 0.05).CONCLUSIONSThe pathological LN response may be a reliable prognostic prediction tool in patients with LAGC who received NAC.

01 Oct 2024·Digestive and Liver Disease

Role of pathological tumor regression grade of lymph node metastasis following neoadjuvant chemotherapy in locally advanced gastric cancer

Article

Author: Zhu, Yanmei ; Zhang, Ning ; Gao, Xiaozhuo ; Zhao, Zehua ; Zhang, Yong ; Gao, Bo ; Zhang, Tao

AIMSTo confirm whether the pathological response of lymph node metastasis (LNM) to neoadjuvant chemotherapy (NCT) can predict the prognosis of patients with gastric cancer (GC).METHODSA total of 979 patients with locally advanced GC were included. χ² test was used to analyze the relationship between LNM TRG and clinicopathological factors. Cox proportional hazards model was used to analyze the relationship between LNM TRG, clinicopathological factors, and overall survival (OS).RESULTSA total of 21,162 lymph nodes were evaluated, with 237 patients (35.4%) in the response group and 433 patients (64.6%) in the non-response group. The non-responsive group was strongly associated with higher ypT, ypN, ypTNM, primary tumor (PT) TRG (all p < 0.001), positive cancer nodules (p = 0.001), and more distant LNM location (p < 0.001). Patients with the same PT TRG but different LNM TRG had different prognosis. There was no difference in OS between the responding and non-responding groups of LNM at location 2, 3, and M. YpN, tumor location, and LNM location were independent prognostic factors.CONCLUSIONSThe combination of LNM TRG and PT TRG could better predict patient prognosis. Lymph node dissection should be routinely performed after NCT to provide the reference of radical resection.

News (Medical) associated with Locally Advanced Gastric Carcinoma

01 Dec 2023

·www.biospace.com

Daiichi Sankyo Demonstrates Breadth and Depth of Oncology Portfolio Across Multiple Cancers with New Data at ESMO Asia, SABCS and ASH

Annual R&D Day to provide overview of data and updated strategy across Daiichi Sankyo R&D pipeline BASKING RIDGE, N.J.--(BUSINESS WIRE)-- Daiichi Sankyo (TSE: 4568) will present new clinical research across its oncology portfolio in multiple types of solid and blood cancers at the 2023 ESMO Asia Congress (#ESMOAsia23), San Antonio Breast Cancer Symposium (#SABCS23) and American Society of Hematology (#ASH23) Annual Meeting prior to its annual R&D Day. Presentation highlights include the first presentation of results from three trials from Daiichi Sankyo’s DXd ADC and hematology portfolio, which include the DESTINY-Gastric06 phase 2 trial of ENHERTU® (trastuzumab deruxtecan) in Chinese patients with previously treated HER2 positive locally advanced/metastatic gastric cancer or gastroesophageal junction adenocarcinoma at ESMO Asia, the DESTINY-Breast08 phase 1b trial of ENHERTU in combination with anastrozole or fulvestrant in patients with HER2 low metastatic breast cancer at SABCS and the VALENTINE-PTCL01 phase 2 trial of valemetostat in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) at ASH. “Our goal is to push the boundaries of science to change the way cancer is treated,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “These data reinforce the breadth and depth of our oncology pipeline and the important progress we are making in developing innovative medicines and exploring combination strategies for patients across a wide range of cancers, including breast, lung, gastric, acute myeloid leukemia and peripheral T-cell lymphoma.” Subgroup analyses of the TROPION-Lung05 phase 2 trial of datopotamab deruxtecan (Dato-DXd) in Asian patients with non-small cell lung cancer (NSCLC) with actionable genomic alterations and the DESTINY-Lung02 phase 2 trial of ENHERTU in Asian patients with HER2 mutant NSCLC will be presented at ESMO Asia. Additional subgroup analyses of the QuANTUM-First phase 3 trial in patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia (AML), which formed the basis of recent approvals of VANFLYTA® (quizartinib) in the EU, Japan and U.S. will be presented at ASH. Daiichi Sankyo will hold its annual R&D Day for investors, analysts and media on Monday, December 11 at 5:30 - 7:00 pm EST/Tuesday, December 12 at 7:30 - 9:00 am JST. Company executives will provide highlights of Daiichi Sankyo’s research data presented at SABCS and ASH, as well as updates on the company’s R&D strategy. ESMO Asia Data Encore presentations of the TROPION-Lung01 phase 3 trial and TROPION-Lung05 phase 2 trial of datopotamab deruxtecan (Dato-DXd) as well as the DESTINY-PanTumor02 phase 2 trial of ENHERTU will be presented at ESMO Asia from December 1 - 3 in Singapore, along with other data, including: Presentation Title Presenter Abstract Presentation ENHERTU (trastuzumab deruxtecan; T-DXd) Lung Trastuzumab deruxtecan (T-DXd) in Asian patients with human epidermal growth factor receptor 2 (HER2; ERBB2) mutant (HER2m) metastatic non–small cell lung cancer: subgroup analysis of DESTINY-Lung02 Y. Goto 510MO Mini-Oral Session December 2, 2023 9:00 – 10:30 am SGT Pan Tumor Trastuzumab deruxtecan (T-DXd) for pretreated patients with HER2 expressing solid tumors: primary analysis from the DESTINY-PanTumor02 study D. Oh 74MO Mini-Oral Session December 1, 2023 10:45 am – 12 :15 pm SGT Gastric Trastuzumab deruxtecan (T-DXd) in Chinese patients with previously treated HER2 positive locally advanced/ metastatic gastric cancer or gastroesophageal junction adenocarcinoma: primary efficacy and safety from the phase 2 single-arm DESTINY-Gastric06 trial L. Shen 172P Poster Presentation December 2, 2023 Datopotamab deruxtecan (Dato-DXd) Lung Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic non-small cell lung cancer: results of the randomized phase 3 study TROPION-Lung01 M. Ahn 509MO Mini-Oral Session December 2, 2023 9:00 – 10:30 SGT TROPION-Lung05: datopotamab deruxtecan (Dato-DXd) in previously treated non-small cell lung cancer with actionable genomic alterations S. Kitazono 518MO Mini-Oral Session Sunday, December 3 9:00 – 10:30 am SGT TROPION-Lung05: datopotamab deruxtecan (Dato-DXd) in Asian patients with previously treated non-small cell lung cancer with actionable genomic alterations Y. Goto 552P Poster Presentation December 2, 2023 SABCS Data Highlights of Daiichi Sankyo data across several subtypes of breast cancer to be presented at SABCS from December 5 - 9 in San Antonio, Texas, include: Presentation Title Author Abstract Presentation ENHERTU (trastuzumab deruxtecan; T-DXd) HER2 Low Breast Trastuzumab deruxtecan (T-DXd) in combination with anastrozole or fulvestrant in patients with HER2 low HR+ advanced/metastatic breast cancer: a phase 1b, open-label, multicenter, dose-expansion study (DESTINY-Breast08) K. Jhaveri RF02-03 Rapid-Fire Mini-Oral December 7, 2023 12:00 – 12:45 pm CST An open-label, interventional multicenter study of trastuzumab deruxtecan monotherapy in patients with unresectable and/or metastatic HER2 low or HER2 immunohistochemistry 0 breast cancer: DESTINY-Breast15 S. Modi PO2-19-06 Poster Presentation December 6, 2023 5:00 – 7:00 pm CST HER2 Positive Breast European real-world experience of patients with HER2+ advanced/metastatic breast cancer accessing trastuzumab deruxtecan through a named patient program: first interim analysis of EUROPA T-DXd M. De Laurentiis PO3-16-12 Poster Presentation December 7, 2023 12:00 – 2:00 pm CST Real-world experience with trastuzumab deruxtecan in patients with breast cancer: 6 month interim analysis of an all patient post marketing surveillance in Japan J. Tsurutani PO3-17-07 Poster Presentation December 7, 2023 12:00 – 2:00 pm CST Population pharmacokinetics of trastuzumab deruxtecan (T-DXd) in HER2 positive breast cancer subjects: analyses across 12 Phase 1-3 studies C. Li PO3-04-01 Poster Presentation December 7, 2023 12:00 – 2:00 pm CST Exposure-efficacy and exposure-safety analysis of trastuzumab deruxtecan in patients with advanced metastatic HER2+ breast cancer: analyses from phase 3 studies DESTINY-Breast02 and DESTINY-Breast03 C. Li PO3-04-02 Poster Presentation December 7, 2023 12:00 – 2:00 pm CST Datopotamab deruxtecan (Dato-DXd) HR Positive Breast Randomized phase 3 study of datopotamab deruxtecan vs chemotherapy for patients with previously treated inoperable or metastatic hormone receptor positive, HER2 negative breast cancer: results from TROPION-Breast01 A. Bardia GS02-01 Oral Presentation December 7, 2023 8:15 - 8:30 am CST TNBC Durvalumab + datopotamab deruxtecan in patients with PD-L1 positive advanced/metastatic triple negative breast cancer: arm 8 of the phase 1b/2, open label, platform BEGONIA study P. Schmid PO1-19-10 Poster Presentation December 6, 2023 12:00 - 2:00 pm CST ASH Data Highlights of Daiichi Sankyo data from its hematology portfolio to be presented at ASH from December 9 - 12 in San Diego, California, include: Presentation Title Presenter Abstract Presentation Valemetostat (EZHARMIA in Japan only) T-cell Lymphoma Efficacy and safety of valemetostat monotherapy in patients with relapsed or refractory peripheral T-cell lymphomas: primary results of the phase 2 VALENTINE-PTCL01 study S. Horwitz 302 Oral Presentation December 9, 2023 4:15 pm PST Valemetostat for relapsed or refractory peripheral T- cell lymphomas: primary results from a phase 1 trial E. Jacobsen 303 Oral Presentation December 9, 2023 4:30 pm PST B-cell Lymphoma Valemetostat for relapsed or refractory B-cell lymphomas: primary results from a phase 1 trial K. Izutsu 1731 Poster Presentation December 9, 2023 5:30 - 7:30 pm PST VANFLYTA (quizartinib) FLT3-ITD AML QuANTUM-First: FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)-specific measurable residual disease (MRD) clearance assessed through induction and consolidation is associated with improved overall survival in newly diagnosed FLT3-ITD+ AML patients A. Perl 832 Oral Presentation December 11, 2023 3:30 pm PST QuANTUM-First: safety by treatment phase and by age in newly diagnosed patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) positive acute myeloid leukemia (AML) H. Erba 972 Oral Presentation December 11, 2023 5:45 pm PST Patient-reported outcomes in acute myeloid leukemia patients with FLT3-ITD mutation receiving quizartinib vs. standard chemotherapy: results from the QuANTUM-First trial E. Oliva 918 Oral Presentation December 11, 2023 4:00 pm PST QuANTUM-First: clinical bridging study for FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) companion diagnostic development J. Rohrbach 4260 Poster Presentation December 11, 2023 6:00 - 8:00 pm PST Kinetics of complete remission (CR) and CR duration and its impact on overall survival (OS) and event-free survival (EFS) in QuANTUM-First P. Montesinos 4254 Poster Presentation December 11, 2023 6:00 - 8:00 pm PST About the DXd ADC Portfolio of Daiichi Sankyo The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, 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. U.S.A. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. Designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, 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. Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 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 need. For more information, please visit .

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