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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04357756




Registration number
NCT04357756
Ethics application status
Date submitted
17/04/2020
Date registered
22/04/2020
Date last updated
13/09/2023

Titles & IDs
Public title
A Study to Assess YH001 in Combination With Toripalimab Injection in Subjects With Advanced Solid Tumors
Scientific title
A First-in-human (FIH), Open-Label, Phase I Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of YH001 in Combination With Toripalimab Injection in Subjects With Advanced Solid Tumors
Secondary ID [1] 0 0
YH001002
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - YH001
Treatment: Drugs - Toripalimab

Experimental: YH001 combined with Toripalimab - All the patients will receive YH001 intravenously as single agent for 21 days followed by combination phase.


Treatment: Drugs: YH001
YH001 will be administered intravenously every three weeks (Q3W) for 15 weeks (5 cycles) at doses of Dose A, Dose B, Dose C, Dose D, Dose E, Dose F and Dose G.

Treatment: Drugs: Toripalimab
Toripalimab will be administered by intravenously (Q3W) by the fixed dose of 240 mg from the 2nd cycle to 5th cycle.
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 1 year
Primary outcome [2] 0 0
Maximum tolerated dose (MTD)
Timepoint [2] 0 0
During Cycle 1 (each cycle is 21 days)
Primary outcome [3] 0 0
Dose-limiting toxicities (DLT)
Timepoint [3] 0 0
During Cycle 1 (each cycle is 21 days)
Secondary outcome [1] 0 0
Area under the serum concentration versus time curve within one dosing interval (AUCtau)
Timepoint [1] 0 0
Up to 1 year
Secondary outcome [2] 0 0
Steady state AUC
Timepoint [2] 0 0
Up to 1 year
Secondary outcome [3] 0 0
Maximum serum concentration (Cmax)
Timepoint [3] 0 0
Up to 1 year
Secondary outcome [4] 0 0
Trough concentration before the next dose is administered (Ctrough)
Timepoint [4] 0 0
Up to 1 year
Secondary outcome [5] 0 0
Time to reach maximum serum concentration (Tmax)
Timepoint [5] 0 0
Up to 1 year
Secondary outcome [6] 0 0
Clearance (CL)
Timepoint [6] 0 0
Up to 1 year
Secondary outcome [7] 0 0
Volume of distribution (Vd)
Timepoint [7] 0 0
Up to 1 year
Secondary outcome [8] 0 0
Terminal half-life (T1/2)
Timepoint [8] 0 0
Up to 1 year
Secondary outcome [9] 0 0
Dose proportionality
Timepoint [9] 0 0
Up to 1 year
Secondary outcome [10] 0 0
Incidence of anti-drug antibodies (ADAs)
Timepoint [10] 0 0
Up to 1 year
Secondary outcome [11] 0 0
Incidence of neutralizing antibodies (NAbs)
Timepoint [11] 0 0
Up to 1 year
Secondary outcome [12] 0 0
Objective response rate (ORR)
Timepoint [12] 0 0
Up to 1 year
Secondary outcome [13] 0 0
Duration of response (DOR)
Timepoint [13] 0 0
Up to 1 year
Secondary outcome [14] 0 0
Time to response (TTR)
Timepoint [14] 0 0
Up to 1 year
Secondary outcome [15] 0 0
Progression free survival (PFS)
Timepoint [15] 0 0
Up to 1 year
Secondary outcome [16] 0 0
Overall survival (OS)
Timepoint [16] 0 0
Up to 1 year
Secondary outcome [17] 0 0
Disease control rate (DCR)
Timepoint [17] 0 0
Up to 1 year
Secondary outcome [18] 0 0
Duration of disease control (DDC)
Timepoint [18] 0 0
Up to 1 year

Eligibility
Key inclusion criteria
- Male or female, aged = 18 years

- Have advanced histologically or cytologically confirmed solid tumor

- Have progressed on after treatment with standard therapies or intolerant of standard
care

- At least 1 unidimensional measurable target lesion per RECIST v1.1

- Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1

- Have life expectancy of at least 12 weeks based on investigator's judgement
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Treated with any investigational drug within 4 weeks prior to the fist dose of study
drug

- Received any anticancer therapy less than 28 days prior to the first administration of
study drug or within 5 half-lives of the therapy agent, whichever is shorter. Prior
palliative radiotherapy to bone metastases = 2 weeks prior to the first dose of YH001
is acceptable

- Subjects with prior anti-CTLA-4 checkpoint inhibitors should be excluded

- Subjects with prior PD-1/L1 treatment intolerate to PD-1/L1 therapy should be excluded

- Subjects with a history of = Grade 3 immune-related adverse events (AEs) resulted from
previous immunotherapy or an AE of any grade that resulted in discontinuation of prior
immunotherapy

- Subjects with a history of = Grade 2 pneumonitis resulted from previous immunotherapy
or with a SpO2 by pulse oximetry < 92% at the screening

- Subjects requiring systemic treatment with corticosteroids (>10 mg/day prednisone or
equivalent) or other immunosuppressive medications within 21 days before the planned
first dose of study drug or has need to be treated while on trial. Inhaled or topical
steroids, and adrenal replacement steroid doses = 10 mg daily prednisone equivalent
are permitted in the absence of active autoimmune disease. Ophthalmologic, nasal and
intra-articular injections of steroids are allowed

- Subjects with concomitant active autoimmune disease, history of autoimmune disease
requiring systemic treatment, or history of autoimmune disease within the two years
prior to study entry. Exceptions are subjects with vitiligo, resolved childhood
asthma/atopy, type I diabetes mellitus or hypothyroidism which can be managed by
replacement therapy

- Primary central nervous system (CNS) malignancies or symptomatic CNS metastases. But
subjects with asymptomatic CNS metastases might be eligible if they have no clinical
evidence of progression since completion of CNS-directed therapy, minimum 4 weeks
between completion of radiotherapy and the first dose of YH001 and are currently not
receiving corticosteroids

- QTc > 450 ms at baseline; no concomitant medications that would prolong the QT
interval; no family history of long QT syndrome

- Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have
not recovered to = Grade 1 per CTCAE v5.0, except alopecia, < Grade 2 sensory
neuropathy

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
21/04/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/10/2022
Sample size
Target
Accrual to date
Final
29
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Blacktown Hospital, Blacktown Cancer and Haematology Centre - Blacktown
Recruitment hospital [2] 0 0
St George Private Hospital - Kogarah
Recruitment hospital [3] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
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 YH001 administered intravenously (IV) in
combination with Toripalimab. The study is designed to determine the safety, tolerability and
maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of YH001 when administered in
combination with Toripalimab to subjects with advanced solid tumors.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04357756
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/ct2/show/NCT04357756