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

Sponsor

Eucure (Beijing) Biopharma Co., Ltd (Industry)

Overall Status

Completed

CT.gov ID

NCT04353102

Collaborator

(none)

Enrollment

Locations

Arm

19.1

Actual Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Malignancies	Drug: YH002	Phase 1

Detailed 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).

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 22, 2020

Actual Primary Completion Date :

Sep 14, 2021

Actual Study Completion Date :

Nov 24, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: YH002 All subject will receive YH002 intravenously as single agent every three weeks (Q3W) for up to 2 years, until intolerable toxicity, confirmed disease progression, withdrawal of consent, or Investigator decision, whichever comes first. Subjects who remain on treatment in the absence of disease progression for more than 2 years may continue to receive study drug through a single patient IND.	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.

Arm

Intervention/Treatment

Experimental: YH002

All subject will receive YH002 intravenously as single agent every three weeks (Q3W) for up to 2 years, until intolerable toxicity, confirmed disease progression, withdrawal of consent, or Investigator decision, whichever comes first. Subjects who remain on treatment in the absence of disease progression for more than 2 years may continue to receive study drug through a single patient IND.

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.

Outcome Measures

Primary Outcome Measures

Number of participants with adverse events and serious adverse events [From screening up to 2 year]
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
Maximum tolerated dose (MTD) [Cycle 1 of each cohort. Duration of one cycle is 3 weeks]
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
Dose-limiting toxicities (DLT) [Cycle 1 of each cohort. Duration of one cycle is 3 weeks]
DLT is defined as a toxicity (adverse event at least possibly related to YH002) occurring during the DLT observation period (the initial 21 days)

Secondary Outcome Measures

Area under the serum concentration versus time curve within one dosing interval (AUCtau) [Up to 2 years]
To determine the pharmacokinetics (PK) profile of YH002
Volume of distribution (Vd) [Up to 2 years]
To determine the pharmacokinetics (PK) profile of YH002
Volume of distribution at steady state (Vss) [Up to 2 years]
To determine the pharmacokinetics (PK) profile of YH002
Maximum serum concentration (Cmax) [Up to 2 years]
To determine the PK profile of YH002 as single agent
Trough concentration before the next dose is administered (Ctrough) [Up to 2 years]
To determine the PK profile of YH002
Time to reach maximum serum concentration (Tmax) [Up to 2 years]
To determine the PK profile of YH002
Clearance (CL) [Up to 2 years]
To determine the PK profile of YH002
Terminal half-life (T1/2) [Up to 2 years]
To determine the PK profile of YH002
Dose proportionality [Up to 2 years]
To determine the PK profile of YH002
Incidence of anti-drug antibodies (ADAs) [Up to 2 years]
To assess the immunogenicity of YH002
Incidence of neutralizing antibodies (NAbs) [Up to 2 years]
To assess the immunogenicity of YH002
Objective response rate (ORR) [Up to 2 years]
To assess the preliminary antitumor activity of YH002
Duration of response (DOR) [Up to 2 years]
To assess the preliminary antitumor activity of YH002
Progression free survival (PFS) [Up to 2 years]
To assess the preliminary antitumor activity of YH002
Time to response (TTR) [Up to 2 years]
To assess the preliminary antitumor activity of YH002
Disease control rate (DCR) [Up to 2 years]
To assess the preliminary antitumor activity of YH002
Duration of disease control (DOC) [Up to 2 years]
To assess the preliminary antitumor activity of YH002

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St George Private Hospital	Kogarah	New South Wales	Australia	2217
2	Macquarie University	Macquarie	New South Wales	Australia	2162
3	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria	Australia	3199