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ONO-7914-01:A Phase I, open-label, uncontrolled, dose escalation study to evaluate the tolerability and safety of ONO-7914 alone and in combination with ONO-4538 in patients with advanced or metastatic solid tumors

ONO-7914-01:Phase I study of ONO-7914 alone and in combination with ONO-4538 in patients with solid tumors

25

Patients with advanced or metastatic solid tumors. Of 25 participants in the Safety Analysis Set, 11 participants (44.0%) were male and 14 participants (56.0%) were female. The median age was 64.0 years (range: 42 to 73), and 12 participants (48.0%) were 65 years and older. All participants were Asian. ECOG Performance Status at baseline was 0 in 16 participants (64.0%) and 1 in 9 participants (36.0%).

A total of 25 participants were enrolled: 3 participants in Cohort 1, 3 participants in Cohort 2, 3 participants in Cohort 3, 4 participants in Cohort 4, 4 participants in Cohort 5, 3 participants in Cohort 6, and 5 participants in Cohort 7. Although Part A (ONO-7914 monotherapy phase) was performed, Part B (combination therapy phase with ONO-7914 and ONO-4538) was not conducted and the study was discontinued early. All participants were withdrawn from the study intervention period: 24 participants (96.0%) discontinued due to progressive disease and 1 participant (4.0%) due to withdrawal by the participant. A total of 14 participants (56.0%) were withdrawn from the follow-up period due to death. Of 25 participants, all participants were included in the Safety Analysis Set and PK Analysis Set.

Adverse events were reported in 18 of 25 participants (72.0%). By cohort, adverse events were reported in 3 participants (100.0%) in Cohort 1, 2 participants (66.7%) in Cohort 2, 3 participants (100.0%) in Cohort 3, 4 participants (100.0%) in Cohort 4, 3 participants (75.0%) in Cohort 5, 2 participants (66.7%) in Cohort 6, and 1 participant (20.0%) in Cohort 7. Study intervention-related adverse events were reported in 7 participants (28.0%). The adverse events by SOC were, in descending order of incidence, General disorders and administration site conditions (6 participants, 24.0%), Gastrointestinal disorders (5 participants, 20.0%), Musculoskeletal and connective tissue disorders (4 participants, 16.0%), Infections and infestations, Investigations, and Skin and subcutaneous tissue disorders (3 participants each, 12.0%). The most common adverse events by PT (reported in 2 or more participants) were pyrexia (6 participants, 24.0%), constipation (3 participants, 12.0%), anaemia, insomnia, and rash maculo-papular (2 participants each, 8.0%). Grade 3 adverse event was reported in 1 participant (4.0%), which was lymphocyte count decreased reported in Cohort 6 and its causal relationship to the study intervention was ruled out. Except for this event, all adverse events were Grade 1 (10 participants, 40.0%) or Grade 2 (7 participants, 28.0%). A total of 14 participants (56.0%) died and primary disease was the only primary cause of death. There were no serious adverse events including adverse events leading to death. There were no adverse events leading to withdrawal of study intervention. Adverse events leading to interruption of study intervention were reported in 1 participant (4.0%), who experienced skin infection (Grade 2) and pneumothorax (Grade 1) and their causal relationships to the study intervention were ruled out. There were no adverse events leading to reduction of study intervention.

1. Primary Outcome The DLT evaluation period was defined as Day 1 to Day 28 of Cycle 1. For 20 participants of the DLT evaluable set, ONO-7914 was administered during the DLT evaluation period according to the preset dose of each cohort. No DLTs were identified during the DLT evaluation period. 2. Secondary Outcome Plasma concentrations of ONO-7914 (prodrug of ONO-SG-154-01) and ONO-SG-154-01 were measured from pre-dose to 24h after the end of dosing on Day 1 and Day 22 of Cycle 1. Plasma concentrations of ONO-7914 and ONO-SG-154-01 rapidly decreased following administration of ONO-7914 and became below the limit of quantification in all cohorts at 24h after the end of dosing. Plasma concentrations of ONO-7914 and ONO-SG-154-01 on Day 22 indicated a similar pattern to those on Day 1. Pharmacokinetic parameters (Cmax and AUC) of ONO-SG-154-01 were generally consistent between Day 1 and Day 22, and dose linearity was generally demonstrated within the dose range of ONO-7914 evaluated up to Cohort 7.

This study was the First-in-Human trial of ONO-7914 for patients with advanced or metastatic solid tumors. No DLTs were identified up to 28 days after the first treatment (DLT evaluation period) in any cohort, and the tolerability of ONO-7914 was confirmed. No association between ONO-7914 dose and the grade or incidence of adverse events and/or clinical laboratory abnormalities was determined, and no safety concerns were identified. ONO-7914 demonstrated a favorable safety profile up to Cohort 7.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031210530

Hirashima Yoshinori

Ono Pharmaceutical Co.,LTD

1-8-2 Kyutaromachi, Chuo-ku Osaka-shi, Osaka-fu Japan

clinical_trial@ono.co.jp

JP Clinical Trial Support Desk

Ono Pharmaceutical Co.,LTD

1-8-2 Kyutaromachi, Chuo-ku Osaka-shi, Osaka-fu Japan

+81-120-278-120

clinical_trial@ono.co.jp

Complete

Jan. 31, 2022

Interventional

non-randomized controlled trial

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1.Patients with advanced or metastatic solid tumor
2.Patients with ECOG performance status of 0 or 1
3.Patients with a life expectancy of at least 3 months

1.Patients with severe complication
2.Patients judged to be incapable of providing consent for reasons such as concurrent dementia

Both

advanced or metastatic solid tumors

ONO-7914 is administered as a single agent or combination with ONO-4538.

Safety and tolerability

Pharmacokinetics for ONO-7914 and ONO-4538

+81-3-3520-0111

Jan. 04, 2022

none