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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04353102




Registration number
NCT04353102
Ethics application status
Date submitted
17/04/2020
Date registered
20/04/2020
Date last updated
22/07/2022

Titles & IDs
Public title
A Study to Evaluate the Safety, Tolerability and How YH002 Enters, Moves Through and Exits the Body in Subjects With Advanced Solid Malignancies
Scientific 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
Secondary ID [1] 0 0
YH002002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Malignancies 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - YH002

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.


Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events and serious adverse events
Timepoint [1] 0 0
From screening up to 2 year
Primary outcome [2] 0 0
Maximum tolerated dose (MTD)
Timepoint [2] 0 0
Cycle 1 of each cohort. Duration of one cycle is 3 weeks
Primary outcome [3] 0 0
Dose-limiting toxicities (DLT)
Timepoint [3] 0 0
Cycle 1 of each cohort. Duration of one cycle is 3 weeks
Secondary outcome [1] 0 0
Area under the serum concentration versus time curve within one dosing interval (AUCtau)
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [2] 0 0
Volume of distribution (Vd)
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
Volume of distribution at steady state (Vss)
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [4] 0 0
Maximum serum concentration (Cmax)
Timepoint [4] 0 0
Up to 2 years
Secondary outcome [5] 0 0
Trough concentration before the next dose is administered (Ctrough)
Timepoint [5] 0 0
Up to 2 years
Secondary outcome [6] 0 0
Time to reach maximum serum concentration (Tmax)
Timepoint [6] 0 0
Up to 2 years
Secondary outcome [7] 0 0
Clearance (CL)
Timepoint [7] 0 0
Up to 2 years
Secondary outcome [8] 0 0
Terminal half-life (T1/2)
Timepoint [8] 0 0
Up to 2 years
Secondary outcome [9] 0 0
Dose proportionality
Timepoint [9] 0 0
Up to 2 years
Secondary outcome [10] 0 0
Incidence of anti-drug antibodies (ADAs)
Timepoint [10] 0 0
Up to 2 years
Secondary outcome [11] 0 0
Incidence of neutralizing antibodies (NAbs)
Timepoint [11] 0 0
Up to 2 years
Secondary outcome [12] 0 0
Objective response rate (ORR)
Timepoint [12] 0 0
Up to 2 years
Secondary outcome [13] 0 0
Duration of response (DOR)
Timepoint [13] 0 0
Up to 2 years
Secondary outcome [14] 0 0
Progression free survival (PFS)
Timepoint [14] 0 0
Up to 2 years
Secondary outcome [15] 0 0
Time to response (TTR)
Timepoint [15] 0 0
Up to 2 years
Secondary outcome [16] 0 0
Disease control rate (DCR)
Timepoint [16] 0 0
Up to 2 years
Secondary outcome [17] 0 0
Duration of disease control (DOC)
Timepoint [17] 0 0
Up to 2 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/04/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/11/2021
Sample size
Target
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St George Private Hospital - Kogarah
Recruitment hospital [2] 0 0
Macquarie University - Macquarie
Recruitment hospital [3] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2162 - Macquarie
Recruitment postcode(s) [3] 0 0
3199 - Frankston

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eucure (Beijing) Biopharma Co., Ltd
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT04353102
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04353102