DS-6157 / Daiichi Sankyo - LARVOL DELTA

Novel antibody-drug conjugates based on DXd-ADC technology. (PubMed, Bioorg Chem) - "This review provides a comprehensive assessment of drugs developed with DXd-ADC technology, with a focus on mechanisms of action, pharmacokinetics studies, preclinical data, and clinical outcomes for DS-8201a, U3-1402, DS-1062a, DS-7300a, DS-6157a, and DS-6000a. By integrating existing data, we aim to provide valuable insights into the current therapeutic status and future prospects of these novel agents."

Journal • Review • Oncology

DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST) (clinicaltrials.gov) - P1 | N=34 | Terminated | Sponsor: Daiichi Sankyo | Completed ➔ Terminated; The study was terminated due to a business decision.

Metastases • Stroma • Trial termination • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • GPR20 • KIT • PDGFRA

A Phase I, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients with Advanced Gastrointestinal Stromal Tumor (Clin Cancer Res) - P1 | N=34 | NCT04276415 | Sponsor: Daiichi Sankyo, Inc. | "A total of 34 patients enrolled. DS-6157a was well tolerated, with DLTs in 4 patients (11.8%) at doses of 6.4 mg/kg, 9.6 mg/kg, and 12.8 mg/kg; the MTD was determined to be 6.4 mg/kg....Four patients (11.8%) experienced serious adverse events related to DS-6157a. Six patients died with 5 due to disease progression and 1 due to DS-6157a-related TEAE. Tumor shrinkage was observed in 7 patients (20.6%), and 1 patient (2.9%) achieved a partial response."

P1 data • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

A Phase 1, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients With Advanced Gastrointestinal Stromal Tumor. (PubMed, Clin Cancer Res) - "Targeting GPR20 with DS-6157a was tolerated in patients with advanced GIST with tumor shrinkage demonstrated in KIT/PDGFRA wild type GIST. However, the study did not proceed further due to lower efficacy outcomes than anticipated."

Journal • Metastases • P1 data • Stroma • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Hematological Disorders • Oncology • Sarcoma • GPR20 • KIT • PDGFRA

A phase 1, multicenter, open-label, first-in-human study of DS-6157a in patients (pts) with advanced gastrointestinal stromal tumor (GIST). (ASCO 2022) - P1 | "DS-6157a was generally well tolerated with early signs of moderate clinical activity. While there were no objective responses in pts with KIT-mutant GIST, tumor shrinkage was observed in all 4 pts with KIT wild-type GIST treated at different doses, including a confirmed PR at the MTD in a pt with SDH-deficient GIST with both SDH B and NF1 mutations."

Clinical • P1 data • Anemia • Constipation • Fatigue • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Hematological Disorders • Hepatology • Leukopenia • Liver Failure • Neutropenia • Oncology • Sarcoma • Thrombocytopenia • GPR20 • KIT • NF1

Daiichi Sankyo Showcases Bold Leadership in Oncology with Survival Improvements for Certain Patients with Cancer at ASCO and EHA (Businesswire) - "Daiichi Sankyo (TSE: 4568) will present new clinical research across its oncology portfolio at the 2022 American Society of Clinical Oncology Scientific Program (#ASCO22) and the European Hematology Association Congress (#EHA22). Presentations, including a Plenary Session (LBA#3) at ASCO featuring the DESTINY-Breast04 trial of ENHERTU® (trastuzumab deruxtecan) and a Presidential Symposium at EHA (S100) highlighting the QuANTUM-First trial of quizartinib, underscore the company’s leadership in developing multiple transformative medicines that significantly improve survival for certain patients with cancer. Both DESTINY-Breast04 and QuANTUM-First data will be featured in press briefings at ASCO and EHA."

Clinical data • Breast Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma

DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST) (clinicaltrials.gov) - P1 | N=35 | Completed | Sponsor: Daiichi Sankyo, Inc. | Active, not recruiting ➔ Completed

Trial completion • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • GPR20 • KIT • PDGFRA

DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST) (clinicaltrials.gov) - P1; N=34; Active, not recruiting; Sponsor: Daiichi Sankyo, Inc.; N=100 ➔ 34; Trial completion date: Oct 2024 ➔ May 2022; Trial primary completion date: May 2024 ➔ Jan 2022

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • GPR20 • KIT • PDGFRA

DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST) (clinicaltrials.gov) - P1; N=100; Active, not recruiting; Sponsor: Daiichi Sankyo, Inc.; Recruiting ➔ Active, not recruiting

Enrollment closed • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • GPR20 • KIT • PDGFRA

Identification and Therapeutic Targeting of GPR20, Selectively Expressed in Gastrointestinal Stromal Tumors, with DS-6157a, a First-In-Class Antibody-Drug Conjugate. (PubMed, Cancer Discov) - "DS-6157a exhibited GPR20 expression-dependent antitumor activity in GIST xenograft models including a GIST model resistant to imatinib, sunitinib, and regorafenib. Pre-clinical pharmacokinetics and safety profile of DS-6157a support its clinical development as a potential novel GIST therapy in patients with resistance, refractory, or intolerance to approved TKIs."

Journal • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

[VIRTUAL] Therapeutic targeting of GPR20, selectively expressed in gastrointestinal stromal tumor (GIST), with DS-6157a, an antibody-drug conjugate (ADC) (AACR-II 2020) - "In addition, DS-6157a showed antitumor activity in a GIST patient-derived xenograft model that was resistant to imatinib, sunitinib, and regorafenib. In preclinical toxicology studies using rats and cynomolgus monkeys, the pharmacokinetics and safety profile of DS-6157a were favorable at up to 200 mg/kg and 30 mg/kg, respectively. These data support the clinical development of DS-6157a as a potential novel GIST therapy with activity in patients that are resistant, refractory, or intolerant to approved TKIs."

Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor • CHEK1 • GPR20 • KIT • PDGFRA • TOP1

Daiichi Sankyo to present new preclinical and translational research from DXd ADC portfolio at AACR Virtual Annual Meeting II (Businesswire) - "Daiichi Sankyo Company, Limited…announced that it will present new preclinical and translational research including a late-breaking poster for several antibody drug conjugates (ADCs) in the company’s oncology portfolio at the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting II to be held June 22 to 24 (#AACR20)… Highlights include findings from a preclinical study of U3-1402 in EGFR mutated non-small cell lung cancer (NSCLC), which assessed pre-treatment with EGFR tyrosine kinase inhibitors (TKIs) on U3-1402 uptake and activity alone and in combination with osimertinib."

Clinical data • Preclinical • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology

Daiichi Sankyo initiates clinical trial with 5th DXd ADC, DS-6157,in collaboration with Sarah Cannon Research Institute (Daiichi Sankyo Press Release) - "Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and Sarah Cannon Research Institute (Sarah Cannon) announced today that the first patient has been dosed in a first-in-human phase 1 study evaluating DS-6157, an investigational GPR20 directed antibody drug conjugate (ADC), in patients with advanced gastrointestinal stromal tumor (GIST)...A total of approximately 100 patients are expected to be enrolled in this study at approximately 10 sites in the U.S., Japan and other countries."

Enrollment open • Trial status • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology

Daiichi Sankyo, Sarah Cannon Research Institute begin phase 1 trial of DS-6157 in patients with advanced gastrointestinal stromal tumor (Pharmabiz) - P1, N=NA; "Daiichi Sankyo Company Limited and Sarah Cannon Research Institute, announced that the first patient has been dosed in a first-in-human phase 1 study evaluating DS-6157, an investigational GPR20 directed antibody drug conjugate (ADC), in patients with advanced gastrointestinal stromal tumor (GIST) who have progressed on, or are intolerant to, standard treatment....'Through the development of the DS-6157 targeted therapy, we are taking a critical step in finding more effective therapies for GIST patients,' said Johanna Bendell, MD..."

Media quote

DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST) (clinicaltrials.gov) - P1; N=100; Not yet recruiting; Sponsor: Daiichi Sankyo, Inc.; Trial completion date: Mar 2025 ➔ Oct 2024; Trial primary completion date: Mar 2025 ➔ May 2024

Clinical • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor • PDGFRA

DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST) (clinicaltrials.gov) - P1; N=100; Recruiting; Sponsor: Daiichi Sankyo, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST) (clinicaltrials.gov) - P1; N=100; Not yet recruiting; Sponsor: Daiichi Sankyo, Inc.

Clinical • New P1 trial