ASP2138 / Xencor, Astellas - LARVOL DELTA

ASP2138 monotherapy or in combination with pembrolizumab and mFOLFOX6 or with ramucirumab and paclitaxel in claudin 18 isoform 2 (CLDN18.2) + locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Phase I/Ib trial (ESMO 2025) - P1 | "Conclusions ASP2138 SC monotherapy and ASP2138 SC in combination with 1L pembrolizumab + mFOLFOX6 or 2L ramucirumab + paclitaxel had a manageable safety profile. Efficacy data for cohorts G and H will be included in the presentation."

Combination therapy • Metastases • Monotherapy • P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • CLDN18 • HER-2

Astellas Doses First Patient in Phase 3 Study of ASP2138 in CLDN18.2-postive and HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (PRNewswire) - "...The ASP2138 Phase 3 study supports the Company's execution of its Corporate Strategic Plan, including its ambition to initiate five or more Phase 3 or pivotal studies by fiscal year 2027....The co-primary endpoints are overall survival and progression-free survival. The study plans to enroll 570 participants across multiple countries."

New P3 trial • Trial status • Gastric Adenocarcinoma • Gastroesophageal Junction Adenocarcinoma

ASP2138: Primary analysis data from P3 trial (NCT07673887) for 1L gastric/GEJ cancer in FY2029 (Astellas) - Q1 FY2026 Results

P3 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology

A Study of ASP2138 Together With Chemotherapy and Pembrolizumab in Adults With Gastric Cancer (clinicaltrials.gov) - P3 | N=570 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • HER-2 • MSI • PD-L1

A Study of ASP2138 Together With Chemotherapy and Pembrolizumab in Adults With Gastric Cancer (clinicaltrials.gov) - P3 | N=570 | Not yet recruiting | Sponsor: Astellas Pharma Global Development, Inc.

New P3 trial • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • HER-2 • MSI • PD-L1

Pipeline Transformation & Clinical Milestones (Investing.com) - "setidegrasib: The company initiated a Phase 3 study in first-line pancreatic ductal adenocarcinoma in April 2026, with primary analysis anticipated in FY2029. ASP2138: The company plans to initiate a Phase 3 study in the first half of FY2026."

New P3 trial • P3 data • Pancreatic Ductal Adenocarcinoma

VTS208: A first-in-class CD3/CLDN18.2/CDH17 Tri-specific T cell engager (TCE) for the treatment of gastrointestinal (GI) cancer (AACR 2026) - "Zolbetuximab (Astellas' anti-CLDN18.2 mAb, approved) has validated CLDN18.2 as a promising tumor-associated antigen (TAA) for gastrointestinal (GI) cancer therapy. CLDN18.2-targeting T cell engagers (TCEs), including IBI389 (phase I) and ASP2138 (phase I), demonstrate anti-tumor activity in patients with low CLDN18.2 expression, indicating that the TCE modality is effective even with minimal TAA expression...Current development includes CMC process optimization and dose-range-finding (DRF) toxicity studies. With mini-pool fermentation titers of 4-6 g/L supporting targeted drug substance concentrations for subcutaneous administration, the IND application is scheduled for filing in H2 2026.In summary, VTS208's unique trispecific design and differentiated features demonstrate promising efficacy and safety, positioning it as a compelling first-in-class TCE candidate for clinical development."

Trispecific • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CDH17 • CLDN18

2138-CL-0101: A Study of ASP2138 Given by Itself or Given With Other Cancer Treatments in Adults With Stomach Cancer, Gastroesophageal Junction Cancer, or Pancreatic Cancer (clinicaltrials.gov) - P1 | N=398 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Trial completion date: May 2027 ➔ May 2028 | Trial primary completion date: Nov 2026 ➔ May 2028

IO biomarker • Monotherapy • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CA 19-9 • HER-2 • PD-L1

ASP2138: “ASP2138 in combination with standard of care drives striking anti-tumor activity in gastric/GEJ adenocarcinoma irrespective of Claudin 18.2 expression”; Gastric/GEJ adenocarcinoma (44th Annual J.P. Morgan Healthcare Conference, Astellas)

P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology

ASP2138: “ASP2138 in combination with standard of care drives striking anti-tumor activity in gastric/GEJ adenocarcinoma irrespective of Claudin 18.2 expression”; Gastric/GEJ adenocarcinoma (44th Annual J.P. Morgan Healthcare Conference, Astellas)

P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology

A Study of ASP2138 Given Before Surgery, Then Chemotherapy After Surgery, in People With Pancreatic Ductal Cancer (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Initiation date: Jul 2025 ➔ Oct 2025

Monotherapy • Trial initiation date • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

ASP2138 monotherapy in patients (pts) with claudin 18 isoform 2 (CLDN18.2)+, advanced solid tumors: Phase I/Ib trial (ESMO 2025) - P1 | "Conclusions This ongoing study suggests that ASP2138 IV monotherapy has a manageable safety profile and promising antitumor activity in pts with CLDN18.2+ LA unresectable or mG/GEJ adenocarcinoma. Efficacy data for pts with mPDAC will be reported at a later date."

Clinical • Metastases • Monotherapy • P1 data • Gastroesophageal Junction Adenocarcinoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • CLDN18 • GZMB • PD-L1

Astellas To Present Pioneering Advances Across Its Portfolio and Pipeline at ESMO 2025 (Astellas Press Release) - "In prostate cancer, we are sharing final best-in-class overall survival data for XTANDI (enzalutamide) in high-risk, biochemically recurrent non-metastatic hormone sensitive disease, plus encouraging data for our next-generation bispecific T cell engager ASP2138 in solid tumors, demonstrating continued leadership in CLDN18.2-targeted precision medicine."

Clinical data • Castration-Resistant Prostate Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Hormone Sensitive Prostate Cancer • Solid Tumor

A Study of ASP2138 Given Before Surgery, Then Chemotherapy After Surgery, in People With Pancreatic Ductal Cancer (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

A Study of ASP2138 Given Before Surgery, Then Chemotherapy After Surgery, in People With Pancreatic Ductal Cancer (clinicaltrials.gov) - P1 | N=25 | Not yet recruiting | Sponsor: Astellas Pharma Global Development, Inc.

Monotherapy • New P1 trial • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

A Study of ASP2138 Given by Itself or Given With Other Cancer Treatments in Adults With Stomach Cancer, Gastroesophageal Junction Cancer, or Pancreatic Cancer (clinicaltrials.gov) - P1 | N=305 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Trial completion date: Dec 2026 ➔ Apr 2027 | Trial primary completion date: Jun 2026 ➔ Oct 2026

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Study of ASP2138 Given by Itself or Given With Other Cancer Treatments in Adults With Stomach Cancer, Gastroesophageal Junction Cancer, or Pancreatic Cancer (clinicaltrials.gov) - P1 | N=305 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Trial completion date: Jun 2026 ➔ Dec 2026

Combination therapy • Metastases • Monotherapy • Trial completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Clinical trials of CD3/CLDN18.2 dual antibodies launched in China; latest data on IBI389 for the treatment of pancreatic cancer and gastric cancer released [Google translation] (new.qq.com) - "On May 30, according to the CDE clinical trial registration and information disclosure platform, Astellas' CD3/CLDN18.2 dual antibody ASP2138 launched a Phase I/Ib study in China, aiming to evaluate the efficacy and safety in patients with metastatic or locally advanced unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma or metastatic pancreatic adenocarcinoma expressing CLDN 18.2 (registration number: CTR20241945)....However the study was registered and launched on ClinicalTrials.gov in May 2022 (registration number: NCT05365581), with a plan to enroll 275 people worldwide, and the first subject was enrolled in June 2022. This time, the domestic part was launched."

Trial status • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of ASP2138 in Adults With Stomach Cancer, Gastroesophageal Junction Cancer, Pancreatic Cancer (clinicaltrials.gov) - P1 | N=275 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

ASP2138, a novel 2+1 format, claudin 18.2 x CD3 bispecific antibody, demonstrates selectivity and activity in preclinical cancer models (AACR 2023) - P1 | "ASP2138 exhibited an antitumor effect on human CLDN18.2-expressing gastric cancer in a human PBMC-engrafted NOG mouse model in vivo. In summary, ASP2138 is expected to show a clinical effect through cytotoxicity against CLDN18.2-expressing tumor cells by T-cell activation that results from selective binding to CLDN18.2 and CD3."

IO biomarker • Preclinical • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CLDN18 • IFNG

A Study of ASP2138 in Adults With Stomach Cancer or Pancreatic Cancer (clinicaltrials.gov) - P1 | N=240 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CA 19-9 • CLDN18 • PD-L1

A Study of ASP2138 in Adults With Stomach Cancer or Pancreatic Cancer (clinicaltrials.gov) - P1 | N=240 | Not yet recruiting | Sponsor: Astellas Pharma Global Development, Inc.

IO biomarker • New P1 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CA 19-9 • CLDN18 • PD-L1