Astellas to Present New Clinical Data Across Its Gastrointestinal Cancers Portfolio at 2026 ASCO GI Cancers Symposium

- Data reflect new insights and precision oncology advancements in portfolio and pipeline -

- Cohort results from Phase 2 ILUSTRO study evaluating a zolbetuximab triplet combination regimen in first-line advanced gastric and gastroesophageal junction (GEJ) cancer featured in late-breaking oral presentation -

TOKYO, Dec. 10, 2025 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") today announced it will present data on potential treatments for pancreatic and gastric/gastroesophageal junction (G/GEJ) cancer at the 2026 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium taking place January 8-10, 2026 in San Francisco, California. Highlights include a late-breaking oral presentation of cohort results from the Phase 2 ILUSTRO study of first-line zolbetuximab in combination with chemotherapy and immunotherapy in claudin 18.2-positive, HER2-negative, locally advanced or metastatic G/GEJ cancer, as well as new Phase 1 data from ASP3082 (setidegrasib), an investigational KRAS G12D targeted protein degrader, in pancreatic cancer.

Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Head of Oncology Development, Astellas
"At Astellas, we are harnessing next-generation treatment modalities and a precision biomarker-driven approach to deliver treatments that make a meaningful difference for patients with gastrointestinal cancers. We're excited to share data at ASCO GI from our growing portfolio of assets in GI cancers – which showcase our commitment to better understanding how to treat these diseases – including emerging data from zolbetuximab as well as progress on ASP3082 (setidegrasib), our investigational KRAS G12D targeted protein degrader. Together with the passionate GI cancer community of patients, physicians, and advocates, we are working to transform outcomes for patients and pave the future of cancer care."

Astellas Presentations at ASCO GI 2026

About Astellas
Astellas is a global life sciences company committed to turning innovative science into VALUE for patients. We provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women's health. Through our research and development programs, we are pioneering new healthcare solutions for diseases with high unmet medical need. Learn more at www.astellas.com.

About VYLOY™ (zolbetuximab)
VYLOY (zolbetuximab) is a first-in-class monoclonal antibody (mAb) specifically designed to target tumor cells that express claudin 18.2 (CLDN18.2), a transmembrane protein. By binding to CLDN18.2, VYLOY (zolbetuximab) induces cancer cell death and inhibits tumor growth by activating two distinct immune system pathways - antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), as demonstrated in preclinical studies.

VYLOY (zolbetuximab) was the first CLDN18.2-targeted therapy to receive regulatory approval anywhere in the world and is currently the only approved treatment, in combination with chemotherapy, for CLDN18.2-positive (HER2-negative) gastric or gastroesophageal junction (GEJ) cancer in several countries, including China, the European Union, Japan, and the United States.

In both the SPOTLIGHT and GLOW Phase 3 clinical trials, which assessed the efficacy and safety of zolbetuximab plus chemotherapy in patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma, approximately 38% of patients screened had tumors that were CLDN18.2 positive, defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18.2 immunohistochemical staining. This represents a substantial patient group that could benefit from targeted first-line therapy.^1,2

Astellas collaborated with Roche on the Ventana™ CLDN18 (43-14a) RXDX assay, which, where approved, can be used by pathologists or laboratories to identify patients eligible for targeted treatment with VYLOY (zolbetuximab).

Astellas is exploring zolbetuximab in combination with pembrolizumab and chemotherapy as a first-line treatment for patients with CLDN18.2-positive, HER2-negative, PD-L1-positive locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma in the investigational Phase III LUCERNA study. For more information, visit clinicaltrials.gov with identifier NCT06901531.

About ASP3082 (setidegrasib)
ASP3082 is a selective protein degrader discovered fully in-house that targets mutated KRAS G12D, which is found in approximately 40% of pancreatic ductal adenocarcinomas.3 A potential first-in-class therapy, ASP3082 is currently being evaluated in a Phase 1 clinical trial for patients with metastatic or locally advanced unresectable solid tumors with KRAS G12D mutations. In addition, Astellas is advancing ASP4396 which also targets mutated KRAS G12D and is in Phase 1 study. For more information, visit clinicaltrials.gov with identifier NCT05382559 (ASP3082) or NCT06364696 (ASP4396).

The safety and efficacy of the agents under investigation have not been established for the uses being considered. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated.

U.S. VYLOY (zolbetuximab-clzb) Indication and Important Safety Information 

INDICATION
VYLOY, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.

Warnings and Precautions

Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated.

Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment. All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity.

ADVERSE REACTIONS
Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia.

Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, decreased phosphate, decreased potassium, and decreased magnesium.

SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6
Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension.

GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX
Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain.

SPECIFIC POPULATIONS
Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose.

Full U.S. Prescribing Information 

Cautionary Notes
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.

References
¹ Shitara K, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023;401(10389):1655-1668.
² Shah MA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29(8):2133-2141.
³ Lee, JK et al. Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors. NPJ Precis Oncol. 2022;9;6(1):91.

SOURCE Astellas Pharma Inc.