DS-3939 / Daiichi Sankyo, Glycotope - LARVOL DELTA

DS-3939, a tumor-associated mucin 1 (TA-MUC1)–directed antibody–drug conjugate (ADC), in patients (pts) with advanced/metastatic (adv/met) solid tumors: Initial results from a first-in-human (FIH) study (ESMO 2025) - P1/2 | "Table: 917O n (%) Dose level Total (N=47) 1 (n=3) 2 (n=3) 3 (n=14) 4 (n=14) 5 (n=12) 6 (n=1) Ongoing treatment 0 1 (33.3) 6 (42.9) 6 (42.9) 6 (50.0) 1 (100) 20 (42.6) TEAE Any 3 (100) 3 (100) 13 (92.9) 14 (100) 12 (100) 1 (100) 46 (97.9) G3+ 0 0 5 (35.7) 6 (42.9) 7 (58.3) 1 (100) 19 (40.4) Drug-related (DR) 2 (66.7) 3 (100) 9 (64.3) 14 (100) 10 (83.3) 1 (100) 39 (83.0) DR G3+ 0 0 2 (14.3) 5 (35.7) 5 (41.7) 1 (100) 13 (27.7) Led to discontinuation 0 1 (33.3) 2 (14.3) 0 2 (16.7) 0 5 (10.6) DLT 0 0 1 (7.1) G3 anemia needing transfusion 1 (7.1) G3 abdominal pain 1 (8.3) G4 platelet count decreased 0 3 (6.4) Adjudicated DR interstitial lung disease* 0 1 (33.3) G2 2 (14.3) G1, G3 0 3 (25.0) all G2 0 6 (12.8) *2 cases at dose level 3 were adjudicated after DCO Conclusions DS-3939 showed manageable safety/tolerability and an early signal of clinical activity in pretreated pts. Part 2 is currently enrolling."

Clinical • First-in-human • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MUC1

A Study of DS-3939a in Participants With Solid Tumors (clinicaltrials.gov) - P1/2 | N=400 | Not yet recruiting | Sponsor: Daiichi Sankyo

New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MUC1

Comparative efficacy of MUC1-C (XYA02) and MUC1-N (PankoMab, DS-3939a analog) antibody-drug conjugates in preclinical NSCLC (AACR 2026) - "Our findings demonstrate that targeting the membrane-tethered MUC1-C subunit with XYA02 provides superior antitumor efficacy compared with MUC1-N-directed DS-3939a analog in preclinical NSCLC models. Enhanced efficacy appears to be driven by uniform antigen binding and potential avoidance of MUC1-N-mediated antigen sink effects. These data support prioritizing MUC1-C-selective ADCs for clinical development in NSCLC and other MUC1-driven malignancies.* https://patents.google.com/patent/US20230265208A1/en"

ADC • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MUC1

DB-1326, a novel dual-payload TA-MUC1-directed antibody-drug conjugate, shows potent antitumor efficacy in pre-clinical tumor model (AACR 2026) - "Several antibody-drug conjugates (ADCs) targeting TA-MUC1 are in development in clinical and preclinical stage, such as DS-3939a, CAT-09-833... DB-1326 is a novel dual-payload ADC with a TA-MUC1 antibody. It displayed high tumor cell selectivity and superior anti-tumor effects in preclinical studies. These findings support the potential of DB-1326 as a promising advanced therapeutic candidate for tumors."

ADC • Preclinical • Oncology • MUC1

DS3939-077: First-in-Human Study of DS-3939a in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=540 | Recruiting | Sponsor: Daiichi Sankyo | Trial primary completion date: Mar 2026 ➔ Oct 2026

First-in-human • Trial primary completion date • Oncology • Solid Tumor • MUC1

A phase 1/2, first-in-human study of DS-3939a in patients with advanced solid tumors: A new DXd ADC targeting TA-MUC1 (AACR 2024) - P1/2 | "Part 2 will also evaluate efficacy by objective tumor response rate per RECIST version 1.1 as a primary endpoint. Secondary endpoints include the disease control rate, duration of response, time to response, progression-free survival, overall survival, TA-MUC1 expression (detected by immunohistochemistry), the pharmacokinetic profile of DS-3939a, and the number of patients with anti-drug antibodies against DS-3939a."

ADC • Clinical • First-in-human • Metastases • P1/2 data • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • MUC1

DS-3939a, a novel TA-MUC1-targeting antibody-drug conjugate (ADC) with a DNA topoisomerase I inhibitor DXd, exhibits potent antitumor activity in preclinical models (AACR 2024) - P1/2 | "Based on these preclinical results, DS-3939a could provide valuable therapy with potential benefits for patients with TA-MUC1-expressing tumors. A first-in-human phase 1/2 study in patients with advanced solid tumors is currently in progress (NCT05875168)."

ADC • First-in-human • Preclinical • Bladder Cancer • Breast Cancer • Oncology • Solid Tumor • MUC1

DS3939-077: First -in-Human Study of DS-3939a in Subjects with Advanced Solid Tumors (clinicaltrialsregister.eu) - P1/2 | N=207 | Recruiting | Sponsor: Daiichi Sankyo Inc. | N=114 ➔ 207

Enrollment change • First-in-human • Oncology • Solid Tumor

…Data were presented today during a proffered paper session (917O) at the 2025 European Society for Medical Oncology (#ESMO25) (Businesswire) - "Preliminary efficacy results were reported across dose levels from 1.0 mg/kg to 10.0 mg/kg of DS-3939. One confirmed complete response was observed in a patient with ovarian cancer and 10 confirmed partial responses were seen in patients with ovarian cancer (n=5), NSCLC (n=4) and breast cancer (n=1). Thirty-nine cases of stable disease were observed in patients with NSCLC (n=11), urothelial carcinoma (n=8), pancreatic ductal adenocarcinoma (n=6), colorectal cancer (n=5), biliary tract cancer (n=4), breast cancer (n=3) and ovarian cancer (n=2) after a median follow-up of 8.8 months (range, 0.6-22.9)."

P1/2 data • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Urothelial Cancer

DS-3939: “Most common TRAEs were gastrointestinal, hematologic, and fatigue; most were Grade 1 or 2”; Solid tumors (Daiichi Sankyo) - ESMO 2025: DS-3939 demonstrated promising preliminary antitumor activity across dose levels and tumor types in previously treated patients”

P1/2 data • Oncology • Solid Tumor

Progress Continues in Multiple Cancers Across the DXd ADC Portfolio of Daiichi Sankyo (Businesswire) - "Data from...TROPION-PanTumor03, DESTINY-Gastric04, DESTINY-CRC02, DESTINY-PanTumor02 and DS-3939 – further support the strength of the DXd ADC portfolio of Daiichi Sankyo across multiple types of cancer....Updates of progress in lung cancer include a mini oral session reporting updated results from a phase 1/2 trial of gocatamig (2758MO), a DLL3 targeting T-cell engager being jointly developed by Merck, in patients with small cell lung cancer and other neuroendocrine cancers, as well as a poster presentation that will highlight the initial safety results from a phase 1b trial of valemetostat (2023P)..."

Clinical data • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Non-Squamous Non-Small Cell Cancer • Neuroendocrine Tumor • Small Cell Lung Cancer • Urothelial Cancer • HER-2

DS3939-077: First-in-Human Study of DS-3939a in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=540 | Recruiting | Sponsor: Daiichi Sankyo | Trial completion date: Jul 2027 ➔ Feb 2027

First-in-human • Trial completion date • Biliary Tract Cancer • Lung Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • MUC1

DS-3939a: A TA-MUC1-directed Antibody-Drug Conjugate with Broad Anti-Tumor Activity. (PubMed, Mol Cancer Ther) - P1/2 | "Moreover, DS-3939a elicited strong tumor regression in several xenograft models even following treatment with other cytotoxic ADCs, likely through its efficient payload delivery. Overall, these data provide evidence for the potential utility of DS-3939a for the treatment of TA-MUC1-expressing tumors and support the rationale for the ongoing phase I/II clinical study (NCT05875168)."

Journal • Bladder Cancer • Breast Cancer • Oncology • Solid Tumor • MUC1

Daiichi Sankyo’s new ADC cancer drug approved for clinical trials in China [Google translation] (vbdata.cn) - "The Class 1 new drug DS-3939a submitted by Daiichi Sankyo has been approved for clinical trials and is intended to be developed to treat solid tumors. Public information shows that DS-3939a is an antibody-drug conjugate (ADC) targeting tumor-related MUC1 and is currently in Phase 1/2 clinical research worldwide. According to the CDE official website, this is the first time that the product has been approved for clinical trials in China. The approval of this innovative ADC for clinical trials in China means that it will enter the clinical research stage in China."

New trial • Oncology • Solid Tumor

A phase 1/2, first-in-human study of DS-3939a in patients with advanced solid tumors: A new DXd ADC targeting TA-MUC1. (ASCO 2024) - P1/2 | "Part 2 will also evaluate efficacy by objective tumor response rate per RECIST version 1.1 as a primary endpoint. Secondary endpoints include the disease control rate, duration of response, time to response, progression-free survival, overall survival, TA-MUC1 expression (detected by immunohistochemistry), the pharmacokinetic profile of DS-3939a, and the number of patients with anti-drug antibodies against DS-3939a."

Clinical • Metastases • P1/2 data • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • MUC1

Daiichi Sankyo Highlights Progress in Creating New Standards of Care for Patients Across Multiple Cancers at ASCO (Businesswire) - "Trials-in-progress presentations include the IDeate-Lung02 phase 3 trial (TPS8126) evaluating ifinatamab deruxtecan (I-DXd) in patients with relapsed small cell lung cancer, the REJOICE-Ovarian01 phase 2/3 trial (TPS5625) evaluating raludotatug deruxtecan (R-DXd) in patients with platinum-resistant ovarian cancer, the HERTHENA-PanTumor01 phase 2 trial (TPS3164) evaluating patritumab deruxtecan (HER3-DXd) in patients with locally advanced or metastatic solid tumors, and the first-in-human phase 1/2 trial (TPS3165) of DS-3939 in patients with advanced solid tumors."

Trial status • Gynecologic Cancers • Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor

DS-3939 Enters Clinical Development in Patients Across Several Types of Advanced Solid Cancers (Businesswire) - "Daiichi Sankyo...announced today that the first patient has been dosed in a first-in-human phase 1/2 trial evaluating DS-3939 in patients with several types of advanced solid tumors including non-small cell lung, breast, urothelial, ovarian, biliary tract, and pancreatic cancer....The two-part, multicenter, open-label, first-in-human phase 1/2 trial will assess the safety and efficacy of DS-3939 in patients with locally advanced, metastatic or unresectable solid tumors not amenable to standard of care treatment for each tumor type....The trial will evaluate safety endpoints including dose-limiting toxicities and adverse events, and efficacy endpoints including overall response rate, disease control rate, duration of response, time to response, progression-free survival and overall survival. Pharmacokinetic and biomarker endpoints also will be assessed."

Trial status • Biliary Tract Cancer • Breast Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Urothelial Cancer

First-in-Human Study of DS-3939a in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=430 | Recruiting | Sponsor: Daiichi Sankyo, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Biliary Tract Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • MUC1

First-in-Human Study of DS-3939a in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=430 | Not yet recruiting | Sponsor: Daiichi Sankyo, Inc.

Metastases • New P1/2 trial • Biliary Tract Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • MUC1