BMS-986310 / BMS, Ono Pharma - LARVOL DELTA

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

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

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

A Study to Investigate the Efficacy and Safety of ONO-4578 in Combination With Nivolumab and Chemotherapy in Chemotherapy-naïve Participants With HER2-negative Unresectable Advanced or Recurrent Gastric Cancer (Including Esophagogastric Junction Cancer) (clinicaltrials.gov) - P2 | N=210 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2027 ➔ Jul 2027

Combination therapy • Enrollment closed • Metastases • Trial completion date • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study to Investigate the Efficacy and Safety of ONO-4578 in Combination With Nivolumab and Chemotherapy in Chemotherapy-naïve Participants With HER2-negative Unresectable Advanced or Recurrent Gastric Cancer (Including Esophagogastric Junction Cancer) (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: Ono Pharmaceutical Co. Ltd

Combination therapy • Metastases • New P2 trial • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Safety and efficacy of ONO-4578 plus nivolumab in metastatic colorectal cancer. (ASCO-GI 2024) - "4578+NIV showed an acceptable safety profile in patients with mCRC, and no new safety signals were detected. 4578+NIV also showed antitumor activity in patients with mCRC. Favorable efficacy was observed in the PD-L1 CPS-positive subpopulation."

Clinical • IO biomarker • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • MSI • PD-L1

Safety, efficacy, and biomarkers for ONO-4578 plus nivolumab in unresectable advanced or recurrent gastric or gastroesophageal cancer (ESMO 2023) - P1 | "Baseline urine PGEM, the potential surrogate marker of tumor PGE2, was higher in pts with PR or SD than in pts with PD, suggesting the contribution of 4578 to the antitumor activity. Conclusions 4578 + NIV demonstrated a manageable safety profile and antitumor activity in pts with G/GEJ cancer."

Biomarker • Clinical • Metastases • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • UGT1A1

[VIRTUAL] Inhibition of PGE2/EP4 pathway by ONO-4578/BMS-986310, a novel EP4 antagonist, promotes T cell activation and myeloid cell differentiation to dendritic cells (AACR-II 2020) - P1, P1/2 | "Finally, a combination of ONO-4578/BMS-986310 and anti-PD-1 antibody results in enhanced anti-tumor effects in GL261 and MC38 tumor-bearing mice compared with anti-PD-1 monotherapy.Our data demonstrate that ONO-4578/BMS-986310 promotes anti-tumor immunity and may be useful in the treatment of cancer patients. ONO-4578/BMS-986310 is being evaluated as monotherapy and in combination with nivolumab in an ongoing Ph1/1b clinical trials in patients with advanced solid tumors (NCT03155061, NCT03661632)."

Brain Cancer • Oncology • Solid Tumor

First-in-human study of ONO-4578, an antagonist of prostaglandin E receptor 4, alone and with nivolumab in solid tumors. (PubMed, Cancer Sci) - P1 | "Considering safety, efficacy, and pharmacokinetics/pharmacodynamics results, ONO-4578 40 mg daily with nivolumab 240 mg biweekly was selected as the recommended dose for future clinical trials. (Registration: JapicCTI-173496 and NCT03155061)."

Journal • P1 data • Dermatology • Lung Cancer • Neuroendocrine Tumor • Oncology • Peptic Ulcer • Small Cell Lung Cancer • Solid Tumor • PTGER4

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; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Monotherapy • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

[VIRTUAL] First in human study of ONO-4578, a PGE2-receptor EP4 antagonist, in monotherapy and combination with PD-1 checkpoint inhibitor nivolumab in patients with advanced or metastatic solid tumours (ESMO 2020) - "Funding: ONO PHARMACEUTICAL CO., LTD. Bristol-Myers Squibb."

Checkpoint inhibition • Clinical • Monotherapy • P1 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • TNFA

Study of ONO-4578 With and Without ONO-4538 in Subjects Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=183; Recruiting; Sponsor: Ono Pharmaceutical Co. Ltd; N=138 ➔ 183; Trial completion date: Mar 2023 ➔ Sep 2025; Trial primary completion date: Mar 2023 ➔ Sep 2025

Clinical • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

An Investigational Immunotherapy Study of BMS-986310 Administered Alone and in Combination With Nivolumab in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=27; Completed; Sponsor: Bristol-Myers Squibb; Recruiting ➔ Completed; N=308 ➔ 27; Trial completion date: Sep 2023 ➔ Dec 2020

Clinical • Combination therapy • Enrollment change • Trial completion • Trial completion date • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI • TNFA