Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

One course will last 28 days. Oral administration at a dose of 80 mg/day, 120mg/day or 160 mg/day for 21 consecutive days, with a 1-week washout period.

Regorafenib

One course will last 28 days. Given once every 2 weeks at a dose of 3.0 mg/kg.

Kohei Shitara, Dr

the efficacy and safety ofhe use of regorafenib in combination with nivolumab

The present trial consists of a dose-escalation cohort to verify the tolerability of nivolumab and regorafenib when used in combination for patients with solid tumors, and to examine the clinical recommended dose(RD). The trial also consists of an expansion cohort to examine the safety and efficacy when the clinical RD is administered for several advanced solid tumors.

In the dose-escalation cohort, three patients with solid tumors will be administered 3.0 mg/kg of nivolumab once every 2 weeks and regorafenib daily for 21days, with a 1-week washout period at dose of 80 mg (level 1), 120 mg (level 2), or 160 mg (level 3). As a general rule, one cycle will last 28 days (day 1-29); however, in the event of treatment prolongation, the cycle period will be extended. The Dose Limiting Toxicity(DLT) evaluation period will be 28 days. Furthermore, for each level, three additional subjects will be added depending on the state of DLT.

In the expansion cohort, the target subject sample will consist of approximately 30 patients who will be administered 3.0 mg/kg of nivolumab once every 2 weeks, and the clinical RD of regorafenib will be determined in the dose-escalation cohort.

Regorafenib and Nivolumab Simultaneous Combination Therapy

Regorafenib and Nivolumab Simultaneous Combination Therapy for Advanced and Metastatic Solid Tumors: Phase I Clinical Trial

Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1, and immune-related (ir) RECIST

Ono Pharmaceutical Co. Ltd

Bayer Yakuhin, Ltd.

Kohei Shitara

Assistant Chief of Gastrointestinal Oncology Division

Antibodies

Immunoglobulins

Immunoconjugates

Immunologic Factors

Participants enrolled in the dose escalation part or dose expansion part

Dose Escalation：Subjects will receive an intravenous infusion of FZ-AD004 in a dose escalation until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.

Dose Expansion：Subject will receive a single dose of FZ-AD004 at 1-2 dose level on Day1 of each cycles.

FZ-AD004

Xuejing Cheng

Shun Lu

This study is one single group of participants with advanced solid tumors. It is the first time the drug has been used in humans. There will be two parts including Dose Escalation and Dose Expansion to evaluate the safety, tolerability, pharmacokinetics, and clinical activity of FZ-AD004.

This is a first-in-human (FIH), Phase 1, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of FZ-AD004 in patients with advanced/metastatic solid tumors. FZ-AD004 is administered via intravenous infusion using an accelerated titration method followed by a conventional 3 + 3 study design to identify the maximum tolerated dose (MTD) and dose-limiting toxicities（DLT）during cycle 1. In addition, the maximum-tolerated dose and recommended Phase II dose for FZ-AD004 will be determined.

A Study of FZ-AD004 in Patients With Advanced Solid Tumors

A PhaseⅠStudy to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of FZ-AD004 in Patients With Advanced Solid Tumors

To determine the dose limiting toxicities (DLTs) of FZ-AD004.

To determine the maximum tolerated dose (MTD) and/or recommended doses for expansion (RDEs). RDEs will not exceed MTD.

To check the numbers of AEs happened during the course of trial.

To evaluate the objective response rate (ORR) \[Complete Response (CR) + Partial Response (PR)\] of FZ-AD004 when administered intravenously (IV) as monotherapy at the RDEs to patients with metastatic or locally advanced unresectable tumors.

Progression-free survival (PFS) was defined as the interval from the first dose start date to the date of disease progression defined as documented progressive disease (PD) or death from any cause, whichever occurs first.

Duration of Response was defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Overall survival was defined as the time from the date of the first dose start date to the date of death due to any cause.

To check how much time Total Antibody, Free DXd and FZ-AD004 will take to eliminate half of it's concentration from participants.

o check what will be the maximum concentration participants will obtained of Total Antibody, Free DXd and FZ-AD004 in their blood plasma.

To check the drug profile for absorption, distribution, metabolism and excretion for Total Antibody, Free DXd and FZ-AD004 in participants blood plasma

To check what time will it take to reach the maximum contraction of Total Antibody, Free DXd and FZ-AD004 in study participants

To check the" Anti Drug Antibody" develops in participants against the FZ-AD004 through blood sample

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Regorafenib and Nivolumab Simultaneous Combination Therapy	NCT03406871	Advanced and Me...	Regorafenib Nivolumab	20 Years -	National Cancer Center Hospital East
A Study of FZ-AD004 in Patients With Advanced Solid Tumors	NCT05914545	Advanced and Me...	FZ-AD004	18 Years - 75 Years	Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.

Spots Global Cancer Trial Database for advanced and metastatic solid tumor