ONO-4578-06:Phase I Study of ONO-4578 and Letrozole Plus CDK4 /6 Inhibitors in Breast Cancer

ONO-4578-06: Phase I , Open-label, Non-blind, First-line Endocrine Therapy With ONO-4578 and Standard Treatment Letrozole and CDK4/6 Inhibitors (Palbociclib or Abemaciclib) in Patients With Metastatic or Recurrent Postmenopausal Hormone Receptor-positive HER2-negative Breast Cancer

This is a multicenter, open-label, non-controlled, phase I study to investigate the tolerability and safety of ONO-4578 used in combination with standard-of-care letrozole and a CDK4/6 inhibitor (palbociclib or Abemaciclib) as first-line endocrine therapy in postmenopausal patients with metastatic or recurrent hormone receptor-positive, HER2-negative breast cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Breast Cancer; Recurrent Breast Cancer; HER2-negative Breast Cancer; Hormone Receptor-positive Breast Cancer
• Intervention / Treatment: Drug: ONO-4578; Drug: letrozole; Drug: Palbociclib; Drug: abemaciclib

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan
      • Aichi Cancer Center Hospital
    • Nagoya-shi, Aichi, Japan
      • Nagoya University Hospital
  • Chiba
    • Chiba-shi, Chiba, Japan
      • Chiba Cancer Center
    • Kashiwa-shi, Chiba, Japan
      • National Cancer Center Hospital East
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan
      • St. Marianna University Hospital
    • Yokohama-shi, Kanagawa, Japan
      • Kanagawa Cancer Center
  • Kyoto
    • Kyoto-shi, Kyoto, Japan
      • University Hospital Kyoto Prefectural University of Medicine
  • Miyagi
    • Sendai-shi, Miyagi, Japan
      • Tohoku University Hospital
  • Osaka
    • Osaka-shi, Osaka, Japan
      • Osaka International Cancer Institute
  • Saitama
    • Ina, Saitama, Japan
      • Saitama Cancer Center
  • Tokyo
    • Chuo-ku, Tokyo, Japan
      • National Cancer Center Hospital
    • Koto-ku, Tokyo, Japan
      • The Cancer Institute Hospital of JFCR
    • Shinjuku-ku, Tokyo, Japan
      • Tokyo Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with postmenopausal metastatic or recurrent breast cancer
2. Patients with ECOG Performance Status 0 to 1
3. ER-positive, PgR-positive and HER2-negative patients

Exclusion Criteria:

1. Patients are unable to swallow oral medications
2. Patients with severe complication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ONO-4578 + letrozole + palbociclib	Drug: ONO-4578; Specified dose on specified days; Drug: letrozole; Specified dose on specified days; Drug: Palbociclib; Specified dose on specified days
Experimental: ONO-4578 + letrozole + abemaciclib	Drug: ONO-4578; Specified dose on specified days; Drug: letrozole; Specified dose on specified days; Drug: abemaciclib; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events	Through study completion, an average of 4 year
Serious adverse events	Through study completion, an average of 4 year
Dose-limiting toxicity (Tolerability Confirmation part only)	28 days
Laboratory abnormality profile of Drugs as measured by incidence and severity of clinical laboratory abnormalities	Through study completion, an average of 4 year
Body temperature	Through study completion, an average of 4 year
Pulse rate	Through study completion, an average of 4 year
Systolic/diastolic blood pressure	Through study completion, an average of 4 year
Saturation of Percutaneous Oxygen (SpO2)	Through study completion, an average of 4 year
Weight	Through study completion, an average of 4 year
Eastern Cooperative Oncology Group Performance Status	Through study completion, an average of 4 year
Chest X-ray	Through study completion, an average of 4 year
CT scan	Through study completion, an average of 4 year
12-lead electrocardiography (Heart rate)	Through study completion, an average of 4 year
12-lead electrocardiography (PR interval)	Through study completion, an average of 4 year
12-lead electrocardiography (RR interval)	Through study completion, an average of 4 year
12-lead electrocardiography (QRS width)	Through study completion, an average of 4 year
12-lead electrocardiography (QT interval)	Through study completion, an average of 4 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall response rate (ORR)	Through study completion, an average of 4 year
Disease control rate (DCR)	Through study completion, an average of 4 year
Clinical benefit rate (CBR)	Through study completion, an average of 4 year
Overall survival (OS)	Through study completion, an average of 4 year
Progression-free survival (PFS)	Through study completion, an average of 4 year
Duration of response (DOR)	Through study completion, an average of 4 year
Time to response (TTR)	Through study completion, an average of 4 year
Best overall response (BOR)	Through study completion, an average of 4 year
Percent change in the sum of diameters of target lesions	Through study completion, an average of 4 year
Maximum percent change in the sum of diameters of target lesions	Through study completion, an average of 4 year
Changes in tumor markers	Through study completion, an average of 4 year
Plasma ONO-4578 concentration	Through study completion, an average of 4 year

Collaborators and Investigators

• Sponsor: Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Project Leader, Ono Pharmaceutical Co. Ltd

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2021
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: July 31, 2024
• First Submitted That Met QC Criteria: August 21, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Actual): July 2, 2025
• Last Update Submitted That Met QC Criteria: June 27, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Breast Cancer; Metastatic; Recurrent; HER2-negative; Hormone Receptor-positive
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Skin Diseases; Breast Diseases; Recurrence; Breast Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Protein Kinase Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Aromatase Inhibitors; Letrozole; Palbociclib
• Other Study ID Numbers: ONO-4578-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No