A Study of ONO-7475 in Patients With Acute Leukemias | NCT03176277

Label	Type	Description	Intervention Names
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)

Name	Type	Description	Arm Group Labels	Other Names
ONO-7475 3mg once daily	Drug	Part A initial dose level	ONO-7475 3mg once daily

Measure	Description	Time Frame
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)

Measure	Description	Time Frame
Determination of Maximum Tolerated Dose (MTD) by Assessing Dose Limiting Toxicities (DLT) (Part A)	Dose Limiting Toxicities (DLT) Criteria: 1) ONO-7475-related ≥Grade 4 hematologic toxicity, 2) any pre-existing condition that worsens by more than 1 grade or to Grade 4, not caused by AML, 3) any ≥Grade 3 non-hematologic toxicity not caused by AML (exception: alopecia, nausea, vomiting, fatigue, headache, chills, electrolyte disturbances), 4) ≥Grade 2 blurred vision (confirmed by loss of 15 letters or more on Early Treatment Diabetic Retinopathy chart and by ophthalmological and retinal assessments) not caused by AML, 5) ≥Grade 2 clinically significant changes in night blindness not caused by AML, 6) ≥Grade 3 differentiation syndrome, 7) death not caused by AML, and 8) any other event determined by the Safety Review Committee for dosing stop. Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was applied for toxicity grading.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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:
1. Total bilirubin within 1.5 x upper limit of normal (ULN), except those with Gilberts syndrome for whom this must be ≤3 x ULN
2. AST and ALT ≤2.5 x ULN
3. Calculated creatinine clearance ≥45 mL/min
4. 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):
1. 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
2. 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).
Diagnosis of AML according to WHO criteria (2016) (Part D only).
Patients with R/R AML who have no standard-of-care options known to provide clinical benefit in patients with R/R AML (Part D only)
1. Refractory AML: Patients who have not achieved complete remission after two cycles of induction chemotherapy (i.e., anthracycline containing regimen), four cycles of hypomethylating agents, or two cycles of other AML therapy
2. Relapsed AML: Patients who have ≥5% BM blasts in BM, or reappearance of blasts in the peripheral blood not attributable to another cause (e.g., recovery of normal cells following chemotherapy-induced aplasia) or (re)appearance of extramedullary disease after CR of prior AML therapy.
Patients must have measured BM aspirate blast counts at Screening. Where the aspirate is hypo cellular or inaspirable a biopsy would be considered.
Patients who were refractory to or relapsed after their 1st line treatment for AML must have received 2 or less additional lines of intensive / aggressive chemotherapy, which also includes a venetoclax-based regimen, as per the latest National Comprehensive Cancer Network (NCCN) Guidelines.

Exclusion Criteria:

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.
Pregnant or lactating women.
Proliferative disease (white blood cell [WBC] counts >30 x 10e9/L) confirmed prior to the first dose of ONO-7475 (for Part A) or WBC >25 x 10e9/L in Part D.
Active malignancy, other than AML (Parts A and D) or MDS (Part A), requiring systemic therapy except for those patients who have been diagnosed with either prostate or breast cancer and who have received a stable dose of hormone therapy for a minimum of 6 months prior to entering this study.
Known hypersensitivity to venetoclax (Part D only).
Calculated creatinine clearance <45 mL/min

Name	Affiliation	Role
Project Leader	Ono Pharmaceutical Co., Ltd.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Southern California		Los Angeles	California	90033	United States
University of California

PubMed Identifier	Type	Citation	Retractions
41385448	Derived	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.

ID	Title	Description
FG000	ONO-7475 3mg	Part A initial dose level
FG001	ONO-7475 6mg	Part A 2nd dose level

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Feb 9, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Safety analysis set, in participants who received at least 1 dose of ONO-7475.

Posted

Count of Participants

Participants

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).

ID	Title	Description
OG000	ONO-7475 3mg	Part A initial dose level
OG001	ONO-7475 6mg	Part A 2nd dose level
OG002	ONO-7475 10 mg	Part A 3rd dose level
OG003	Total	Part A total

Units	Counts
Participants	OG00010 OG0013 OG0027 OG003

Title

Denominators

Categories

Anaemia

Title	Measurements
	OG0004 OG0011 OG0022 OG003

Primary

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.

Safety analysis set, in participants who received at least 1 dose of ONO-7475.

Posted

Count of Participants

Participants

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).

ID	Title	Description
OG000	ONO-7475 3mg	Part A initial dose level
OG001	ONO-7475 6mg	Part A 2nd dose level
OG002	ONO-7475 10mg	Part A 3rd dose level
OG003	Total	Part A total

Primary

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.

Safety analysis set, in participants who received at least 1 dose of ONO-7475.

Posted

Count of Participants

Participants

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).

ID	Title	Description
OG000	ONO-7475 3mg	Part A initial dose level
OG001	ONO-7475 6mg	Part A 2nd dose level
OG002	ONO-7475 10mg	Part A 3rd dose level
OG003	Total	Part A total

Primary

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

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

Safety analysis set, in participants who received at least 1 dose of ONO-7475.

Posted

Count of Participants

Participants

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).

ID	Title	Description
OG000	ONO-7475 3mg	Part A initial dose level
OG001	ONO-7475 6mg	Part A 2nd dose level
OG002	ONO-7475 10mg	Part A 3rd dose level
OG003	Total	Part A total

Units	Counts

Primary

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.

Safety analysis set, in participants who received at least 1 dose of ONO-7475 and/or venetoclax.

Posted

Count of Participants

Participants

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).

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D ONO-7475 + venetoclax group

Units	Counts
Participants	OG000

Primary

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.

Safety analysis set, in participants who received at least 1 dose of ONO-7475 and/or venetoclax.

Posted

Count of Participants

Participants

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).

ID	Title	Description
OG000	ONO-7475 6 mg + Venetoclax	Part D ONO-7475 6 mg + Venetoclax

Units	Counts
Participants	OG000

Primary

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.

Full analysis set

Posted

Count of Participants

Participants

From baseline up to maximum of 21 months

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D ONO-7475 + venetoclax

Units	Counts
Participants	OG00022

Secondary

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

Dose Limiting Toxicities (DLT) Criteria: 1) ONO-7475-related ≥Grade 4 hematologic toxicity, 2) any pre-existing condition that worsens by more than 1 grade or to Grade 4, not caused by AML, 3) any ≥Grade 3 non-hematologic toxicity not caused by AML (exception: alopecia, nausea, vomiting, fatigue, headache, chills, electrolyte disturbances), 4) ≥Grade 2 blurred vision (confirmed by loss of 15 letters or more on Early Treatment Diabetic Retinopathy chart and by ophthalmological and retinal assessments) not caused by AML, 5) ≥Grade 2 clinically significant changes in night blindness not caused by AML, 6) ≥Grade 3 differentiation syndrome, 7) death not caused by AML, and 8) any other event determined by the Safety Review Committee for dosing stop.

Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was applied for toxicity grading.

Analysis set included participants evaluable for DLT, defined as participants received ONO-7475 with a minimum dose intensity of 75% within DLT evaluation period [from first dose to Day 28] and had completed Day 28 assessments.

Posted

Count of Participants

Participants

28 days

ID	Title	Description
OG000	ONO-7475 3mg	Part A Initial dose level
OG001	ONO-7475 6mg	Part A 2nd dose level

Secondary

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

Part A Pharmacokinetics Cmax of ONO-7475 assessed on day 1 and day 28, and Ctrough of ONO-7475 assessed on day 28 (pre-dose).

Pharmacokinetic (PK) analysis set, in participants who received at least 1 dose of ONO-7475 and with evaluable PK parameter resulted were summarised.

Posted

Mean

Standard Deviation

ng/mL

Day 1 and Day 28

ID	Title	Description
OG000	ONO-7475 3mg	Part A initial dose level
OG001	ONO-7475 6mg	Part A 2nd dose level
OG002	ONO-7475 10mg	Part A 3rd dose level

Units	Counts
Participants	OG000

Secondary

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

Part A Pharmacokinetics Tmax of ONO-7475 assessed on day 1 and day 28.

Pharmacokinetic (PK) analysis set, in participants who received at least 1 dose of ONO-7475 and with evaluable PK parameter resulted were summarised. Insufficient evaluable data available for day 28 Tmax values in 3 mg dose group.

Posted

Mean

Standard Deviation

Hour (h)

Day 1 and Day 28

ID	Title	Description
OG000	ONO-7475 3mg	Part A initial dose level
OG001	ONO-7475 6mg	Part A 2nd dose level
OG002	ONO-7475 10mg	Part A 3rd dose level

Units	Counts
Participants	OG000

Secondary

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

Part A Pharmacokinetics (AUC0-10h) of ONO-7475 assessed on day 1 and day 28, (AUC0-24h) of ONO-7475 assessed on day 1.

Pharmacokinetic (PK) analysis set, in participants who received at least 1 dose of ONO-7475 and with evaluable PK parameter resulted were summarised.

Posted

Mean

Standard Deviation

ng*h/mL

Day 1 and Day 28

ID	Title	Description
OG000	ONO-7475 3mg	Part A initial dose level
OG001	ONO-7475 6mg	Part A 2nd dose level
OG002	ONO-7475 10mg	Part A 3rd dose level

Units	Counts
Participants	OG000

Secondary

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

Part A Pharmacokinetics T1/2 of ONO-7475 assessed on day 1 and day 28. T1/2 was not calculable due to insufficient evaluable data.

Pharmacokinetic (PK) analysis set, in participants who received at least 1 dose of ONO-7475 and with evaluable PK parameter resulted were summarised. T1/2 was not calculable due to insufficient evaluable data.

Posted

Day 1 and Day 28

ID	Title	Description
OG000	ONO-7475 3 mg	Part A initial dose level
OG001	ONO-7475 6 mg	Part A 2nd dose level
OG002	ONO-7475 10mg	Part A 3rd dose level

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics of the Food Effect on ONO-7475 (Part A)

Part A Pharmacokinetics (Cmax, Tmax, AUC, T1/2, Ctrough) of the food effect on ONO-7475 assessed as ratio of Day57/Day28 and comparing pharmacokinetic parameters from dosing under fasted and non-fasted conditions assessed in 6mg and 10mg dose groups.

Pharmacokinetic analysis set, in participants who received at least 1 dose of ONO-7475 and with evaluable PK parameter results. Food effect was not evaluated in 3mg dose group. Tmax, T1/2 and Ctrough ratios were not calculable due to insufficient data.

Posted

Median

Full Range

ratio

Day 28 and Day 57

ID	Title	Description
OG000	ONO-7475 3 mg	Part A initial dose level
OG001	ONO-7475 6mg	Part A 2nd dose level
OG002	ONO-7475 10mg	Part A 3rd dose level

Units	Counts
Participants

Secondary

Pharmacodynamics (Axl and Mer Inhibition) of ONO-7475 (Part A)

Assessment of the pharmacodynamic activity by measurement of Axl and Mer inhibition using a Plasma Inhibitory Activity (PIA) assay. PIA is a flow cytometry assay measuring auto-phosphorylation in Axl-expressing Ba/F3 and Mer-expressing Ba/F3 cells, respectively the percentage of inhibition. Pre-dose samples were collected for the analysis on day 2 and day 28.

Pharmacodynamic (PD) analysis set, in participants who received at least 1 dose of ONO-7475 and with evaluable PD parameter results were summarised.

Posted

Mean

Standard Deviation

percentage

Day 2 and Day 28

ID	Title	Description
OG000	ONO-7475 3mg	Part A initial dose level
OG001	ONO-7475 6mg	Part A 2nd dose level
OG002	ONO-7475 10mg	Part A 3rd dose level

Units	Counts
Participants

Secondary

Overall Response Rate and Duration of Response in ONO-7475 Groups (Part A)

Part A analysis of best overall response. Duration of response analysis was not performed as no response of complete remission, Morphologic complete remission with incomplete blood count recovery, morphologic leukemia-free state, or partial remission was observed.

Full analysis set

Posted

Count of Participants

Participants

From baseline up to maximum of 32 months

ID	Title	Description
OG000	ONO-7475 3mg	Part A initial dose level
OG001	ONO-7475 6mg	Part A 2nd dose level
OG002	ONO-7475 10 mg	Part A 3rd dose level
OG003	Total	Part A total

Units	Counts

Secondary

Event Free Survival in ONO-7475 Groups (Part A)

Part A analysis of event free survival in ONO-7475 treatment groups

Full analysis set

Posted

Median

95% Confidence Interval

Months

From baseline up to maximum of 32 months

ID	Title	Description
OG000	ONO-7475 3mg	Part A initial dose level
OG001	ONO-7475 6mg	Part A 2nd dose level
OG002	ONO-7475 10 mg	Part A 3rd dose level
OG003	Total	Part A total

Units	Counts
Participants

Secondary

Pharmacokinetics (Cmax) of ONO-7475 in Treatment Group ONO-7475 + Venetoclax (Part D)

Part D Pharmacokinetics (Cmax) of ONO-7475 in treatment group ONO-7475 + venetoclax.

Pharmacokinetic (PK) analysis set, in participants who received at least 1 dose of ONO-7475 and with evaluable PK parameter results.

Posted

Mean

Standard Deviation

ng/mL

Day 29

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D combination treatment group of ONO-7475 6mg + venetoclax

Units	Counts
Participants	OG00015

Secondary

Pharmacokinetics (Tmax) of ONO-7475 in Treatment Group ONO-7475 + Venetoclax (Part D)

Part D Pharmacokinetics (Tmax) of ONO-7475 in treatment group ONO-7475 + venetoclax.

Pharmacokinetic (PK) analysis set, in participants who received at least 1 dose of ONO-7475 and with evaluable PK parameter results.

Posted

Mean

Standard Deviation

Hour (h)

Day 29

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D combination treatment group of ONO-7475 6mg + venetoclax

Units	Counts
Participants	OG00015

Secondary

Pharmacokinetics (AUC) of ONO-7475 in Treatment Group ONO-7475 + Venetoclax (Part D)

Part D Pharmacokinetics (AUC) of ONO-7475 in treatment group ONO-7475 + venetoclax.

Pharmacokinetic (PK) analysis set, in participants who received at least 1 dose of ONO-7475 and with evaluable PK parameter results.

Posted

Mean

Standard Deviation

ng*h/mL

Day 29

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D combination treatment group of ONO-7475 6mg + venetoclax

Units	Counts
Participants	OG00015

Secondary

Pharmacokinetics (T1/2) of ONO-7475 in Treatment Group ONO-7475 + Venetoclax (Part D)

Part D Pharmacokinetics (T1/2) of ONO-7475 in treatment group ONO-7475 + venetoclax.

Pharmacokinetic (PK) analysis set, in participants who received at least 1 dose of ONO-7475 and with evaluable PK parameter results. T1/2 of ONO-7475 was not calculable due to insufficient evaluable data.

Posted

Day 29

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D combination treatment group of ONO-7475 6mg + venetoclax

Units	Counts
Participants	OG0000

Secondary

Pharmacokinetics (Cmax) of Venetoclax in Treatment Group ONO-7475 + Venetoclax (Part D)

Part D Pharmacokinetics (Cmax) of Venetoclax in treatment group ONO-7475 + Venetoclax.

Pharmacokinetic (PK) analysis set, in participants who received at least 1 dose of venetoclax and with evaluable PK parameter results.

Posted

Mean

Standard Deviation

ng/mL

Day 1 and Day 29

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D combination treatment group of ONO-7475 6mg + venetoclax

Units	Counts
Participants	OG00017

Secondary

Pharmacokinetics (Tmax) of Venetoclax in Treatment Group ONO-7475 + Venetoclax (Part D)

Part D Pharmacokinetics (Tmax) of Venetoclax in treatment group ONO-7475 + venetoclax.

Pharmacokinetic (PK) analysis set, in participants who received at least 1 dose of ONO-7475 and with evaluable PK parameter results.

Posted

Mean

Standard Deviation

Hour (h)

Day 1 and Day 29

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D combination treatment group of ONO-7475 6mg + venetoclax

Units	Counts
Participants	OG00022

Secondary

Pharmacokinetics (AUC) of Venetoclax in Treatment Group ONO-7475 + Venetoclax

Part D Pharmacokinetics (AUC) of Venetoclax in treatment group ONO-7475 + venetoclax.

Pharmacokinetic (PK) analysis set, in participants who received at least 1 dose of venetoclax and with evaluable PK parameter results.

Posted

Mean

Standard Deviation

ng*h/mL

Day 1 and Day 29

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D combination treatment group of ONO-7475 6mg + venetoclax

Units	Counts
Participants	OG00022

Secondary

Pharmacokinetics (T1/2) of Venetoclax in Treatment Group ONO-7475 + Venetoclax (Part D)

Part D Pharmacokinetics (T1/2) of Venetoclax in treatment group ONO-7475 + venetoclax.

Pharmacokinetic (PK) analysis set, in participants who received at least 1 dose of Venetoclax and with evaluable PK parameter results.

Posted

Mean

Standard Deviation

Hour (h)

Day 29

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D combination treatment group of ONO-7475 6mg + venetoclax

Units	Counts
Participants	OG0001

Secondary

Incidence of Adverse Events in ONO-7475 + Venetoclax Group (Part D)

Part D Incidence (frequency > 20%) and severity (CTCAE grades) of treatment-emergent adverse events in ONO-7475 + Venetoclax Group, in preferred terms coded MedDRA version 23.1.

CTCAE = common terminology criteria for adverse events (CTCAE) version 4.03.

Safety analysis set, in participants who received at least 1 dose of ONO-7475 and/or venetoclax.

Posted

Count of Participants

Participants

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).

ID	Title	Description
OG000	ONO-7475 6 mg + Venetoclax (All Grade)	Part D treatment group of ONO-7475 6 mg + Venetoclax
OG001	ONO-7475 6 mg + Venetoclax (Grade >/=3)	Part D treatment group of ONO-7475 6 mg + Venetoclax

Units	Counts
Participants	OG000

Secondary

Incidence of Serious Adverse Events in ONO-7475 + Venetoclax Group (Part D)

Part D Incidence (frequency ≥ 2 participants) and severity (CTCAE grades) of serious treatment-emergent adverse events in ONO-7475 + Venetoclax Group (Part D), preferred term coded with MedDRA version 23.1.

CTCAE = Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Safety analysis set, in participants who received at least 1 dose of ONO-7475 and/or venetoclax

Posted

Count of Participants

Participants

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).

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax (All Grades)	Part D ONO-7475 6mg + Venetoclax
OG001	ONO-7475 6mg + Venetoclax (≥ Grade 3)	Part D ONO-7475 6mg + venetoclax

Units	Counts
Participants	OG000

Secondary

Overall Response Rate in ONO-7475 + Venetoclax Group (Part D)

Part D Summary of best overall response in ONO-7475 + Venetoclax group.

Full analysis set

Posted

Count of Participants

Participants

From baseline up to maximum of 21 months

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax (Part D)	Part D ONO-7475 6mg + venetoclax group

Units	Counts
Participants	OG00022

Secondary

Duration of Response in ONO-7475 + Venetoclax Group (Part D)

Part D Duration of response in ONO-7475 6mg + Venetoclax group.

Full analysis set. Participants with best response assessed as complete remission, complete remission with partial hematologic recovery, complete remission with incomplete hematologic recovery, morphologic leukemia free state and partial remission were included in analysis.

Posted

Mean

Standard Deviation

Months

From baseline up to maximum of 21 months

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D ONO-7475 6mg + Venetoclax

Units	Counts
Participants	OG000

Secondary

Event-Free Survival and Overall Survival in ONO-7475 + Venetoclax Group (Part D)

Part D analysis of event free survival and overall survival in ONO-7475 6mg + Venetoclax group

Full analysis set

Posted

Median

95% Confidence Interval

Months

From baseline up to maximum of 21 months

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D ONO-7475 + venetoclax group

Units	Counts
Participants	OG00022

Secondary

Transfusion Independence Rate (Part D)

Part D analysis of transfusion Independence rate. Rate of maintenance of transfusion independence = percentage of patients who were transfusion independent post-baseline based upon the patients who were transfusion independent at baseline.

Calculated using the Clopper-Pearson method.

Full analysis set and in participants who were transfusion independent at baseline.

Posted

Number

95% Confidence Interval

percentage of participants

From baseline up to maximum of 21 months

ID	Title	Description
OG000	ONO-7475 6mg + Venetoclax	Part D ONO-7475 + venetoclax group

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0003 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG0030 affected22 at risk
Sepsis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0003 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Klebsiella bacteraemia	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Klebsiella sepsis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Arthritis infective	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Bacteraemia	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Cellulitis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Influenza	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Pneumonia respiratory syncytial viral	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Respiratory syncytial virus bronchitis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Stenotrophomonas sepsis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Streptococcal bacteraemia	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
COVID-19	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Enterocolitis infectious	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Herpes simplex oesophagitis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Pneumonia bacterial	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0011 affected3 at risk EG0024 affected7 at risk EG003
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Neutropenic colitis	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Allergic transfusion reaction	Injury, poisoning and procedural complications	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Syncope	Nervous system disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Multiple organ dysfunction syndrome	General disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Ischaemic hepatitis	Hepatobiliary disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
White blood cell count decreased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Differentiation syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0003 affected10 at risk EG0012 affected3 at risk EG0024 affected7 at risk EG0035 affected22 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0004 affected10 at risk EG0010 affected3 at risk EG0022 affected7 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0003 affected10 at risk EG0012 affected3 at risk EG0020 affected7 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0003 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0003 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Fluid overload	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Hypernatraemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Hypovolaemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Lactic acidosis	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Malnutrition	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Tumour lysis syndrome	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0005 affected10 at risk EG0012 affected3 at risk EG0022 affected7 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0005 affected10 at risk EG0012 affected3 at risk EG0022 affected7 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0003 affected10 at risk EG0012 affected3 at risk EG0022 affected7 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0003 affected10 at risk EG0012 affected3 at risk EG0021 affected7 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Gingival hypertrophy	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Oral mucosa haematoma	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Poor dental condition	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Post-tussive vomiting	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Umbilical hernia	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Fatigue	General disorders	MedDRA version 23.1.	Systematic Assessment	EG0003 affected10 at risk EG0012 affected3 at risk EG0022 affected7 at risk EG003
Oedema peripheral	General disorders	MedDRA version 23.1.	Systematic Assessment	EG0004 affected10 at risk EG0012 affected3 at risk EG0021 affected7 at risk EG003
Pyrexia	General disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0010 affected3 at risk EG0022 affected7 at risk EG003
Asthenia	General disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0021 affected7 at risk EG003
Chills	General disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0021 affected7 at risk EG003
Generalised oedema	General disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Mucosal inflammation	General disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Infusion site pain	General disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Malaise	General disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Pain	General disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0004 affected10 at risk EG0011 affected3 at risk EG0022 affected7 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0021 affected7 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Coagulopathy	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Splenic infarction	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Splenomegaly	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Spontaneous haematoma	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Pneumonia	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Sinusitis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Cellulitis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Enterococcal bacteraemia	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Enterococcal infection	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Enterococcal sepsis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Enterocolitis infectious	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Mastitis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Muscle abscess	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Otitis externa	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Skin infection	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Stenotrophomonas sepsis	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Systemic candida	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0022 affected7 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0012 affected3 at risk EG0020 affected7 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Headache	Nervous system disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0011 affected3 at risk EG0022 affected7 at risk EG003
Lethargy	Nervous system disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Syncope	Nervous system disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Dizziness	Nervous system disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Encephalopathy	Nervous system disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Haemorrhage intracranial	Nervous system disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Memory impairment	Nervous system disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Tremor	Nervous system disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0005 affected10 at risk EG0011 affected3 at risk EG0021 affected7 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0003 affected10 at risk EG0011 affected3 at risk EG0021 affected7 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0003 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Lung opacity	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0011 affected3 at risk EG0021 affected7 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0011 affected3 at risk EG0021 affected7 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Eye contusion	Injury, poisoning and procedural complications	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Iliotibial band syndrome	Injury, poisoning and procedural complications	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Platelet count decreased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0011 affected3 at risk EG0021 affected7 at risk EG003
International normalised ratio increased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
White blood cell count increased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Blood lactic acid increased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Neutrophil count decreased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Retinogram abnormal	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
White blood cell count decreased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Weight decreased	Investigations	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA version 23.1.	Systematic Assessment	EG0003 affected10 at risk EG0012 affected3 at risk EG0021 affected7 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Urine odour abnormal	Renal and urinary disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Cataract cortical	Eye disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Conjunctival haemorrhage	Eye disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Eyelid ptosis	Eye disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Night blindness	Eye disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Retinal aneurysm	Eye disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Retinal thickening	Eye disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Retinopathy	Eye disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Scleral haemorrhage	Eye disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Vision blurred	Eye disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Vitreous floaters	Eye disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Hypotension	Vascular disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0022 affected7 at risk EG003
Hypertension	Vascular disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Axillary vein thrombosis	Vascular disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Haematoma	Vascular disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Restrictive cardiomyopathy	Cardiac disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Macule	Skin and subcutaneous tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Seborrhoeic dermatitis	Skin and subcutaneous tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Skin mass	Skin and subcutaneous tissue disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Insomnia	Psychiatric disorders	MedDRA version 23.1.	Systematic Assessment	EG0002 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Anxiety	Psychiatric disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Depression	Psychiatric disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0021 affected7 at risk EG003
Confusional state	Psychiatric disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Cerumen impaction	Ear and labyrinth disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0011 affected3 at risk EG0020 affected7 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Leukaemic retinopathy	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Testicular pain	Reproductive system and breast disorders	MedDRA version 23.1.	Systematic Assessment	EG0001 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003
Transfusion reaction	Injury, poisoning and procedural complications	MedDRA version 23.1.	Systematic Assessment	EG0000 affected10 at risk EG0010 affected3 at risk EG0020 affected7 at risk EG003

ID	Term
D009190	Myelodysplastic Syndromes
D007938	Leukemia
D007951	Leukemia, Myeloid
D015470	Leukemia, Myeloid, Acute

ID	Term
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

ID	Title	Description
BG000	ONO-7475 3mg	Part A initial dose level
BG001	ONO-7475 6mg	Part A 2nd dose level
BG002	ONO-7475 10mg	Part A 3rd dose level
BG003	ONO-7475 6mg + Venetoclax	Part D combination of ONO-7475 + Venetoclax
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	ONO-7475 3mg (Part A)	Part A ONO-7475 initial dose level 3mg	10	10	9	10	10	10
EG001	ONO-7475 6mg (Part A)	Part ONO-7475 2nd dose level 6mg	3	3	2	3	3	3
EG002	ONO-7475 10mg (Part A)	Part A ONO-7475 3rd dose level 10mg	5	7	6	7	7	7
EG003	ONO-7475 6mg + Venetoclax (Part D)	Part D combination of ONO-7475 6mg + venetoclax	15	22	13	22	21	22