BMS-986310 / BMS, Ono Pharmaceutical, Deciphera Pharmaceuticals - LARVOL DELTA

A phase 2 study to evaluate 2 doses of ONO-4578 + nivolumab + mFOLFOX6 + bevacizumab vs SoC for first-line non–MSI-H/dMMR, PD-L1+ advanced CRC (ESMO 2026) - No abstract available

Clinical • dMMR • Metastases • MSI-H • P2 data • Oncology • MSI • PD-L1

The Role of Immunotherapy in the Treatment of Metastatic Gastric Cancer (IASGO 2026) - "HERIZON-GEA-01 showed thatzanidatamab plus chemotherapy improved progression-free survival versus trastuzumab pluschemotherapy, while adding tislelizumab also produced an encouraging overall-survival benefit...Nivolumab plus ipilimumab failed to improve survival in CheckMate 649, andATTRACTION-6 increased response rate without improving overall survival and caused greater toxicity.However, in MSI-H/dMMR advanced G/GEJC, the phase II NO LIMIT trial showed robust and durableactivity with first-line nivolumab plus low-dose ipilimumab, supporting biomarker-defined dualcheckpoint blockade...The EP4 antagonist ONO-4578 plus nivolumab and chemotherapy showed encouragingphase II activity. ASP2138, a CLDN18.2/CD3 bispecific T-cell engager, is being evaluated withpembrolizumab and chemotherapy, while zolbetuximab plus nivolumab and chemotherapy showedpromising activity in ILUSTRO and is being tested in phase III LUCERNA. Future progress will depend on biomarker-driven combinations..."

IO biomarker • Metastases • Gastric Cancer • Oncology • Solid Tumor • CLDN18 • HER-2 • MSI • PD-L1 • TIGIT

Study of ONO-4578 With and Without ONO-4538 in Subjects Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=183 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co., Ltd. | Trial completion date: Mar 2027 ➔ Mar 2028 | Trial primary completion date: Mar 2027 ➔ Mar 2028

Monotherapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastric Cancer • Oncology • Solid Tumor

EP4 Antagonist ONO-4578 Plus Nivolumab and Chemotherapy in HER2-Negative Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer. (PubMed, J Clin Oncol) - "This study demonstrated promising efficacy and acceptable safety of an ONO-4578 regimen as first-line treatment for HER2-negative unresectable advanced or recurrent G/GEJC. These findings warrant confirmation in a phase 3 trial."

Journal • Gastric Cancer • Hematological Disorders • Oncology • Solid Tumor • HER-2 • PD-L1

A Trial of ONO-4578 Versus Placebo in Combination With Nivolumab and Chemotherapy in Participants With Gastric Cancer, Esophagogastric Junction Cancer, or Esophageal Adenocarcinoma (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: Ono Pharmaceutical Co., Ltd.

New P3 trial • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Oncology • Solid Tumor • PD-L1

ONO-4578 combined with nivolumab (NIVO) and chemotherapy (chemo) as first-line (1L) treatment for patients with HER2-negative unresectable advanced or recurrent (adv/rec) gastric/gastroesophageal junction cancer (G/GEJ): A randomized, double-blind, phase 2 trial (ONO-4578-08). (ASCO 2026) - P2 | "Patients in each group received ONO-4578 40 mg or placebo once daily, and all received NIVO 360 mg every 3 weeks and chemo (SOX [S-1 + oxaliplatin]/CAPOX [capecitabine + oxaliplatin])... ONO-4578 combined with NIVO and chemo significantly improved PFS compared with placebo combined with NIVO and chemo in treatment-naive patients with HER2-negative unresectable adv/rec G/GEJ cancer with no new safety concerns."

Clinical • IO biomarker • Metastases • P2 data • Oncology • Solid Tumor • HER-2 • PD-L1

Ono Pharma Announces Oral Presentation of New Data from the Phase 2 Clinical Study of ONO-4578 (EP4 antagonist) in Certain Gastric Cancers at the ASCO 2026 Annual Meeting (Businesswire) - "The ONO-4578 group demonstrated a statistically significant improvement of PFS compared to the placebo with a median PFS of 9.0 months in the ONO-4578 group and 6.9 months in the placebo group (HR, 0.67; 90% CI, 0.48–0.92; P = 0.040). The ONO-4578 group also showed improvements in overall survival (OS) and objective response rate (ORR). Median OS was not reached in the ONO-4578 combination group and 12.7 months in the placebo combination group (HR, 0.60; 95% CI, 0.37–0.96). ORR was 62.0% and 48.7%, respectively (odds ratio, 1.72; 95% CI, 0.98–3.00). Clinical benefit was more pronounced in patients with PD-L1 CPS ≥1...Ono and its affiliate company, Deciphera, plan to initiate a pivotal phase 3 clinical study."

New P3 trial • P2 data • Gastric Cancer • Gastroesophageal Cancer

ONO-4578-06:Phase I Study of ONO-4578 and Letrozole Plus CDK4 /6 Inhibitors in Breast Cancer (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Ono Pharmaceutical Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Ono Pharma Announces Upcoming Presentations at the ASCO 2026 Annual Meeting (Businesswire)

P2 data • P3 data • Gastric Cancer • Gastroesophageal Cancer

ONO-4578-10: A study to evaluate the safety and efficacy of two dose levels of ONO-4578 with Opdivo, in combination with mFOLFOX6 and bevacizumab versus standard of care in participants with non MSI-H/dMMR, PD-L1 positive advanced colorectal cancer. (clinicaltrialsregister.eu) - P1/2 | N=76 | Recruiting | Sponsor: Ono Pharmaceutical Co. Ltd.

dMMR • MSI-H • New P1/2 trial • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • BRAF • PD-L1

A Study to Evaluate the Safety and Efficacy of Two Dose Levels of ONO-4578 With Opdivo®, in Combination With mFOLFOX6 and Bevacizumab Versus Standard of Care in Participants With Non-MSI-H/dMMR, PD-L1 Positive Advanced Colorectal Cancer (clinicaltrials.gov) - P2 | N=144 | Recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2025 ➔ Nov 2025

dMMR • Enrollment open • MSI-H • Trial initiation date • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor

Ono Announces ONO-4578 (EP4 antagonist) in Combination with Opdivo and Chemotherapy Met the Primary Endpoint in a Phase 2 Clinical Trial in Patients with Certain Gastric Cancer (Ono Pharmaceuticals Press Release) - "In the trial, ONO-4578 in combination with Opdivo and chemotherapy demonstrated a statistically significant prolongation of progression-free survival (PFS) compared with placebo in combination with Opdivo and chemotherapy. In addition, no new safety concerns were identified in the trial. Ono will publish the results at an upcoming academic meeting."

P2 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

ONO-4578 Plus Nivolumab in Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer. (PubMed, Cancer Sci) - P1 | "In conclusion, ONO-4578 plus nivolumab showed a manageable safety profile and antitumor activity in G/GEJ cancer. Trial Registration: Japan Registry of Clinical Trials number: jRCT2080223441; ClinicalTrials.gov identifier: NCT03155061."

IO biomarker • Journal • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

ONO-4578-06:Phase I Study of ONO-4578 and Letrozole Plus CDK4 /6 Inhibitors in Breast Cancer (clinicaltrials.gov) - P1 | N=46 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | Trial completion date: Jul 2025 ➔ Apr 2026 | Trial primary completion date: Jul 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Study of ONO-4578 With and Without ONO-4538 in Subjects Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=183 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | Trial completion date: Jan 2026 ➔ Mar 2027 | Trial primary completion date: Jan 2026 ➔ Mar 2027

Monotherapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastric Cancer • Solid Tumor

Neoadjuvant ONO-4578, an EP4 antagonist, in combination with nivolumab after chemoradiation therapy in locally advanced resectable rectal cancer. (ASCO 2025) - P | " Pts with LARC who received preoperative CRT (50.4 Gy with capecitabine 1,650 mg/m2) were eligible. Neoadjuvant 4578 plus NIV after CRT showed a manageable safety profile and promising pCR rates and MPR rates in pts with LARC."

Clinical • Combination therapy • Metastases • Colorectal Cancer • Endocrine Disorders • Gastroenterology • Gastrointestinal Disorder • Hepatology • Hypertension • Liver Failure • Oncology • Rectal Cancer • Solid Tumor

A Study to Evaluate the Safety and Efficacy of Two Dose Levels of ONO-4578 With Opdivo®, in Combination With mFOLFOX6 and Bevacizumab Versus Standard of Care in Participants With Non-MSI-H/dMMR, PD-L1 Positive Advanced Colorectal Cancer (clinicaltrials.gov) - P2 | N=144 | Not yet recruiting | Sponsor: Ono Pharmaceutical Co. Ltd

New P2 trial • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor

Ono Pharma Announces an Oral Presentation on Phase 2 Data for Tirabrutinib and a Poster Session on ONO-4578 (EP4 Antagonist) at the American Society of Clinical Oncology (ASCO) Annual Meeting (Businesswire) - "Positive data from the Phase 2 PROSPECT Study of tirabrutinib in U.S. patients with relapsed or refractory primary central nervous system lymphoma (PCNSL) will be presented in a rapid oral session. Data on the neoadjuvant ONO-4578 (EP4 antagonist) in combination with nivolumab for rectal cancer will be presented in a poster session."

Clinical data • Diagnostic • CNS Lymphoma • Oncology • Rectal Cancer

ONO-4578-04: An Open-label, Uncontrolled Study of ONO-4578 and ONO-4538 in Combination With Standard-of-care Modified FOLFIRINOX (mFFX) or Gemcitabine Plus Nab-paclitaxel (GnP) Therapy as First-line Treatment in Patients With Metastatic Pancreatic Cancer (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Ono Pharmaceutical Co. Ltd | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

ONO-4578-04: An Open-label, Uncontrolled Study of ONO-4578 and ONO-4538 in Combination With Standard-of-care Modified FOLFIRINOX (mFFX) or Gemcitabine Plus Nab-paclitaxel (GnP) Therapy as First-line Treatment in Patients With Metastatic Pancreatic Cancer (clinicaltrials.gov) - P1 | N=46 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | Trial completion date: Nov 2024 ➔ Mar 2025

Combination therapy • Metastases • Trial completion date • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Safety, efficacy, and biomarkers of ONO-4578, an EP4 antagonist, in combination with nivolumab and chemotherapy in treatment-naive and proficient mismatch repair (pMMR)/microsatellite stable (MSS) metastatic colorectal cancer (mCRC) (ESMO-GI 2024) - "This ONO-4578-02, open-label, phase 1 study assessed the safety, preliminary efficacy, and biomarkers of 4578 in combination with NIV and chemotherapy (Chemo) in treatment-naive pMMR/MSS mCRC. Patients received 4578 (40 mg) daily and NIV (360 mg) every 3 weeks in addition to chemo (capecitabine, oxaliplatin, bevacizumab). The combination of 4578 with NIV and Chemo demonstrated a manageable safety profile in patients with pMMR/MSS mCRC, along with promising antitumor activities, particularly in those with a CPS of ≥1."

Biomarker • Clinical • Combination therapy • IO biomarker • Metastases • Mismatch repair • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • PD-L1

ONO-4578-06:Phase I Study of ONO-4578 and Letrozole Plus CDK4 /6 Inhibitors in Breast Cancer (clinicaltrials.gov) - P1 | N=46 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co. Ltd

Metastases • New P1 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Study of ONO-4578 With and Without ONO-4538 in Subjects Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=183 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | Trial completion date: Sep 2025 ➔ Jan 2026 | Trial primary completion date: Sep 2025 ➔ Jan 2026

Metastases • Monotherapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

An Open-label, Uncontrolled Study of ONO-4578 and ONO-4538 in Combination With Standard-of-care Docetaxel and Ramucirumab as Second-line Therapy in Patients With Advanced or Recurrent Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=42 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co. Ltd

Combination therapy • Metastases • New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Study of ONO-4578 and XELOX/FOLFOX Plus Bevacizumab in Colorectal Cancer (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co. Ltd

Combination therapy • Metastases • New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor