A Study to Evaluate the Safety, Tolerability and How YH002 Enters, Moves Through and Exits the Body in Subjects With Advanced Solid Malignancies

Advanced Solid Malignancies Clinical Trial

Official title:

A First-in-Human (FIH), Multicenter, Open-Label, Phase 1 Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of YH002 in Subjects With Advanced Solid Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04353102
• Other study ID #: YH002002
• Status: Completed
• Phase: Phase 1
• Start date: April 22, 2020
• Est. completion date: November 24, 2021

Study information

• Verified date: July 2022
• Source: Eucure (Beijing) Biopharma Co., Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, dose-escalation study of the study drug YH002. The study is designed to determine the safety, tolerability and maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of YH002 in patients with advanced solid Malignancies

Description:

This is a single arm clinical trial in subjects with advanced solid tumor receiving multiple doses of YH002 intravenously (IV). YH002 will be administered (IV) in 6-48 patients with advanced solid tumors. An accelerated titration method followed by a traditional 3+3 dose escalation algorithm will be utilized to determine MTD/MAD. Patients will be dosed at Dose A, Dose B, Dose C, Dose D, Dose E, Dose F, Dose G, and Dose H every 3 weeks (Q3W).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: November 24, 2021
• Est. primary completion date: September 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female, aged = 18 years

• Confirmed as histologically or cytologically, locally advanced or metastatic non-resectable solid tumors, must have received and progressed on, or been ineligible for, or intolerant of available standard therapies known to confer clinical benefit or for whom no standard therapy exits

• Subjects enrolled in Dose D, Dose E, Dose F, Dose G, and Dose H cohorts must have at least one measurable lesion per RECIST v1.1

• Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 and life expectancy no less than 3 months

• Recovery, to Grade 0-1, from adverse events related to prior anticancer therapy except alopecia, < Grade 2 sensory neuropathy, lymphopenia, and endocrinopathies controlled with hormone replacement therapy

Exclusion Criteria:

• Symptomatic central nervous system (CNS) metastases. Subjects with asymptomatic CNS metastases who are radiologically and neurologically stable = 4 weeks following CNS- directed therapy, and do not require corticosteroids or anticonvulsants are eligible for study entry

• Received anticancer therapy or radiation therapy within 5 half-lives or 4 weeks prior to study entry, whichever is shorter

• Received palliative radiotherapy to a single area of metastasis within 2 weeks prior to study entry

• Received agonist antibodies to TNFR such as anti-CD137, OX40, CD27 and CD357 antibodies prior to the study entry

• Allergy or sensitivity to YH002, or known allergies to antibodies produced from Chinese hamster ovary cells which assessed to increase the potential for an adverse hypersensitivity to YH002 by Investigator

• History of a Grade 3-4 allergic reaction to treatment with another monoclonal antibody

• Grade =3 irAEs or irAEs that lead to discontinuation of prior immunotherapy. Hypothyroidism, Type 1 DM, and dermatologic irAEs (except previous Steven Johnson Syndrome, toxic epidermal necrolysis, or other severe forms of dermatitis). Type 1 DM should be controlled with reduction of toxicity to Grade 1 or less

• Concomitant active autoimmune disease or history of autoimmune disease requiring systemic treatment or history of autoimmune disease within 2 years prior to study entry (except vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus or hypothyroidism which can be managed by replacement therapy)

• Received steroids or other immunosuppressive systemic therapy within 4 weeks prior to the first dose of the study drug, or has need to be treated during the study (except using on low systemic absorption location prevent or treat non- autoimmune condition)

• Active hepatitis B or C. Hepatitis B carriers without active disease or cured Hepatitis C may be enrolled

• Severe cardiovascular disease within 6 months of study entry

Related Conditions & MeSH terms

• Advanced Solid Malignancies
• Neoplasms

Intervention

Drug:
• YH002
YH002 will be administered intravenously every three weeks (Q3W) for up to 2 years at doses of Dose A, Dose B, Dose C, Dose D, Dose E, Dose F, Dose G, and Dose H.

Locations

Country	Name	City	State
Australia	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria
Australia	St George Private Hospital	Kogarah	New South Wales
Australia	Macquarie University	Macquarie	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Eucure (Beijing) Biopharma Co., Ltd

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events and serious adverse events	The safety profile of YH002 will be assessed by monitoring the adverse events (AE) per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0	From screening up to 2 year
Primary	Maximum tolerated dose (MTD)	MTD is defined as the highest dose level at which no more than 1 out of 6 subjects experiences a DLT during the first cycle	Cycle 1 of each cohort. Duration of one cycle is 3 weeks
Primary	Dose-limiting toxicities (DLT)	DLT is defined as a toxicity (adverse event at least possibly related to YH002) occurring during the DLT observation period (the initial 21 days)	Cycle 1 of each cohort. Duration of one cycle is 3 weeks
Secondary	Area under the serum concentration versus time curve within one dosing interval (AUCtau)	To determine the pharmacokinetics (PK) profile of YH002	Up to 2 years
Secondary	Volume of distribution (Vd)	To determine the pharmacokinetics (PK) profile of YH002	Up to 2 years
Secondary	Volume of distribution at steady state (Vss)	To determine the pharmacokinetics (PK) profile of YH002	Up to 2 years
Secondary	Maximum serum concentration (Cmax)	To determine the PK profile of YH002 as single agent	Up to 2 years
Secondary	Trough concentration before the next dose is administered (Ctrough)	To determine the PK profile of YH002	Up to 2 years
Secondary	Time to reach maximum serum concentration (Tmax)	To determine the PK profile of YH002	Up to 2 years
Secondary	Clearance (CL)	To determine the PK profile of YH002	Up to 2 years
Secondary	Terminal half-life (T1/2)	To determine the PK profile of YH002	Up to 2 years
Secondary	Dose proportionality	To determine the PK profile of YH002	Up to 2 years
Secondary	Incidence of anti-drug antibodies (ADAs)	To assess the immunogenicity of YH002	Up to 2 years
Secondary	Incidence of neutralizing antibodies (NAbs)	To assess the immunogenicity of YH002	Up to 2 years
Secondary	Objective response rate (ORR)	To assess the preliminary antitumor activity of YH002	Up to 2 years
Secondary	Duration of response (DOR)	To assess the preliminary antitumor activity of YH002	Up to 2 years
Secondary	Progression free survival (PFS)	To assess the preliminary antitumor activity of YH002	Up to 2 years
Secondary	Time to response (TTR)	To assess the preliminary antitumor activity of YH002	Up to 2 years
Secondary	Disease control rate (DCR)	To assess the preliminary antitumor activity of YH002	Up to 2 years
Secondary	Duration of disease control (DOC)	To assess the preliminary antitumor activity of YH002	Up to 2 years