A Study of ONO-7475 in Patients With Acute Leukemias

NCT03176277 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: ONO-7475-01
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 16

Brief Summary

\[Updated\]: To assess the safety and tolerability of ONO-7475 monotherapy in patients with relapsed or refractory acute myeloid leukemia or relapsed or refractory myelodysplastic syndromes and to assess: i) safety and tolerability and ii) preliminary efficacy of the combination of ONO-7475 and venetoclax in patients with relapsed or refractory acute myeloid leukemia.

Conditions

Acute Leukemia; Myelodysplastic Syndromes

Keywords

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; MER; MERTK; TYRO3; AXL; AML; Relapsed/ Refractory AML; TAM; MDS; Myelodysplastic Syndrome; Relapsed/ Refractory MDS

Outcome Measures

Primary Outcomes (7)

• Incidence of Adverse Events (Part A)

  Incidence of most common (frequency of \>20%) treatment-emergent adverse events (TEAEs) of CTCAE grade 3 or higher by preferred terms coded with MedDRA version 23.1. CTCAE = Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  From start of study drug up to 30 days after permanent discontinuation of study drug or initiation of new anti-cancer therapy, whichever occurs first (maximum of 32 months).

• Incidence of Serious Adverse Events (Part A)

  Incidence (frequency ≥ 2 participants) of serious treatment-emergent adverse events (all CTCAE grades) by preferred terms coded with MedDRA version 23.1. CTCAE = Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  From start of study drug up to 30 days after permanent discontinuation of study drug or initiation of new anti-cancer therapy, whichever occurs first (maximum of 32 months).

• Clinically Significant Changes in Ophthalmology Examination Parameters (Part A)

  Incidence (all participants) of ophthalmological treatment-emergent adverse events (all CTCAE grades) by preferred terms coded with MedDRA Version 23.1. CTCAE = Common Terminology Criteria for Adverse Event version 4.03.

  From start of study drug up to 30 days after permanent discontinuation of study drug or initiation of new anti-cancer therapy, whichever occurs first (maximum of 32 months).

• Clinically Significant Changes in 12-Lead Electrocardiogram Parameters (Part A)

  Participants with clinically significant changes in 12-lead Electrocardiogram (ECG) parameters.

  From start of study drug up to 30 days after permanent discontinuation of study drug or initiation of new anti-cancer therapy, whichever occurs first (maximum of 32 months).

• Incidence of Adverse Events (Part D)

  Incidence of most common (frequency \> 20%) treatment-emergent adverse events (TEAEs) of CTCAE grade 3 or higher by preferred term coded with MedDRA version 23.1. CTCAE = Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  From start of study drug up to 30 days after permanent discontinuation of study drug or initiation of new anti-cancer therapy, whichever occurs first (maximum of 21 months).

• Incidence of Serious Adverse Events (Part D)

  Incidence (frequency ≥ 2 participants) of serious treatment-emergent adverse events (all CTCAE grades) by preferred terms coded with MedDRA version 23.1. CTCAE = Common Terminology Criteria for Adverse Events (CTXAE) Version 4.03.

  From start of study drug up to 30 days after permanent discontinuation of study drug or initiation of new anti-cancer therapy, whichever occurs first (maximum of 21 months).

• Complete Response (CR) / Complete Response With Partial Hematologic Recovery (CRh) Rate (Part D)

  Summary of complete response (CR) and complete response with partial hematologic recovery (CRh) rate.

  From baseline up to maximum of 21 months

Secondary Outcomes (23)

• Determination of Maximum Tolerated Dose (MTD) by Assessing Dose Limiting Toxicities (DLT) (Part A)

  28 days

• Pharmacokinetics (Cmax and Ctrough) of ONO-7475 (Part A)

  Day 1 and Day 28

• Pharmacokinetics (Tmax) of ONO-7475 (Part A)

  Day 1 and Day 28

• Pharmacokinetics (AUC) of ONO-7475 (Part A)

  Day 1 and Day 28

• Pharmacokinetics (T1/2) of ONO-7475 (Part A)

  Day 1 and Day 28

Study Arms (4)

ONO-7475 3mg once daily

EXPERIMENTAL

Part A Initial dose level

Drug: ONO-7475 3mg once daily

ONO-7475 6mg once daily

EXPERIMENTAL

Part A 2nd dose level

Drug: ONO-7475 6mg once daily

ONO-7475 10mg once daily

EXPERIMENTAL

Part A 3rd dose level

Drug: ONO-7475 10mg once daily

ONO-7475 6mg + Venetoclax (70-400mg)

EXPERIMENTAL

Part D ONO-7475 + Venetoclax combination

Drug: ONO-7475 6mg + Venetoclax (70-400mg)

Interventions

ONO-7475 3mg once daily DRUG

Part A initial dose level

Also known as: Part A initial dose level

ONO-7475 3mg once daily

ONO-7475 6mg once daily DRUG

Part A 2nd dose level

Also known as: Part A 2nd dose level

ONO-7475 6mg once daily

ONO-7475 10mg once daily DRUG

Part A 3rd dose level

Also known as: Part A 3rd dose level

ONO-7475 10mg once daily

ONO-7475 6mg + Venetoclax (70-400mg) DRUG

Part D ONO-7475 + Venetoclax Combination

Also known as: ONO-7475 + Venetoclax Combination

ONO-7475 6mg + Venetoclax (70-400mg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥18 years at time of screening.
• Written informed consent by the patient (or their legal representative) prior to admission to this study. In addition, any locally required authorization (Health Insurance Portability and Accountability Act in the US), must be obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
• Adequate renal and hepatic function defined as:
• Total bilirubin within 1.5 x upper limit of normal (ULN), except those with Gilberts syndrome for whom this must be ≤3 x ULN
• AST and ALT ≤2.5 x ULN
• Calculated creatinine clearance ≥45 mL/min
• Serum albumin ≥2.5 g/dL For any patient with laboratory values outside the ranges outlined above that are considered due to the patient's underlying disease (AML or MDS), the patient may be enrolled into the study following consultation between the Investigator and the Sponsor's Medical Officer, if the patient is likely to benefit from receiving ONO-7475 (based on the Investigator's assessment).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 as assessed during the screening period and then again anytime during the 2-day period immediately preceding the start of dosing in Parts A and D.
• Life expectancy of at least 3 months
• Sexually active female patients of childbearing potential and sexually active male patients must agree to use an effective method of birth control (e.g., barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices) during the entire duration of the study and for 4 months after final administration of study drug. Note that sterility in female patients must be confirmed in the patients' medical records and be defined as any of the following: surgical hysterectomy with bilateral oophorectomy, bilateral tubular ligation, natural menopause with last menses \>1 year ago, radiation-induced oophorectomy with last menses \>1 year ago, chemotherapy-induced menopause with last menses \>1 year ago.
• Diagnosis of AML or MDS according to WHO criteria 2016 (Part A only).
• Either criterion is met (Part A only):
• Patients with R/R AML with at least 5% blasts by BM biopsy or aspirate, or at least 1% blasts in peripheral blood, not likely to benefit from standard salvage chemotherapy
• Patients with R/R MDS who are either not eligible for (or unlikely to benefit from) other forms of therapy, including HSCT, according to the treating Physician/Investigator .
• All patients must have received at least one previous line of therapy (Part A only).

You may not qualify if:

• Patients with active central nervous system leukemia.
• QT interval corrected according to Fredericia's formula (QTcF) prolongation defined as a QTcF interval \>470 msec or other significant ECG abnormalities including second degree (type II) or third degree atrioventricular block or bradycardia (ventricular rate \<50 beats/min).
• Clinically significant liver disease, including active viral or other hepatitis, current alcohol abuse, or severe cirrhosis.
• Human immunodeficiency virus (HIV), active hepatitis B (HBV) or C (HCV) infection.
• Retinal disease (e.g., retinitis pigmentosa including Mertk mutations), retinal hemorrhage or any disorder which may inhibit follow up for retinal toxicity.
• Serious intercurrent medical or psychiatric illness that will prevent participation or compliance with study procedures, including serious active infection (including COVID-19).
• Acute promyelocytic leukemia (the French-American-British M3 classification).
• Patients not recovered to Grade 1 or stabilized from the effects (excluding alopecia) of any prior therapy for their malignancies.
• Concurrent treatment with other investigational drugs.
• Daily requirement of ≥10 mg/day of prednisone or equivalent dose of other corticosteroids.
• Prior HSCT within 12 weeks of the first dose of study treatment or ongoing immunosuppressive therapy for graft-versus-host disease.
• Participation in another clinical trial with any investigational drug within 14 days or with any licensed drug within five half-lives, prior to the first ONO-7475 dosing (for Part A) or prior to the first venetoclax dosing (for Part D).
• Prior AML or MDS therapy (non-experimental) within 14 days or 5 half-lives, whichever is longer, prior to the first dose of ONO-7475 (for Part A) or prior to the first venetoclax dosing (for Part D) (except those permitted in Section 7.1) and no residual toxicity from the prior therapy hindering of the ONO-7475 dosing (for Part A) or ONO-7475 plus venetoclax dosing (for Part D).
• Prior radiotherapy within 21 days of screening, with the exception of localized palliative radiotherapy.
• Patients undergoing current treatments for other cancers.

Sponsors & Collaborators

• Ono Pharmaceutical Co. Ltd: lead

Study Sites (16)

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California

Los Angeles, California, 90095, United States

Location

Yale University School of Medicine - Yale Cancer Center

North Haven, Connecticut, 06510, United States

Location

University of Florida (UF) - Shands Cancer Center

Gainesville, Florida, 32610, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

The Winship Cancer Institute Emory University

Atlanta, Georgia, 30322, United States

Location

Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

The Ohio State University (OSU)

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina - Hollins Cancer Center

Charleston, South Carolina, 29425, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah - Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Kasner MT, Courtenay-Luck N, DiNardo C, Post SM, Baratam P, Magrath GN, Nakamura T, Fujii A, Prados S, Honda N, Mcbride M, Edwards-Holmes P, Stuart R. Anexelekto (Axl)/Mer Inhibitor Tamnorzatinib in Patients with Relapsed/Refractory Acute Myeloid Leukaemia: Results from a Phase I (Monotherapy) and Phase II (Combination with Venetoclax) Clinical Study. Acta Haematol. 2025 Dec 12:1-11. doi: 10.1159/000549340. Online ahead of print.

  PMID: 41385448 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Medical Information Center
• Organization: Ono Pharmaceutical Co., Ltd.

trials.uk-eu@ono-pharma.com

Please see email

Study Officials

• Project Leader

  Ono Pharmaceutical Co. Ltd

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: ONO-7475 open-label, dose escalation in R/R AML or R/R MDS Part D: ONO-7475 plus venetoclax open-label, dose escalation in R/R AML

Study Record Dates

• First Submitted: May 19, 2017
• First Posted: June 5, 2017
• Study Start: June 26, 2017
• Primary Completion: December 1, 2022
• Study Completion: January 20, 2023
• Last Updated: July 15, 2024
• Results First Posted: May 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)