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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/NCT04481009




Registration number
NCT04481009
Ethics application status
Date submitted
17/07/2020
Date registered
22/07/2020
Date last updated
12/12/2022

Titles & IDs
Public title
A Study to Evaluate YH003 in Combination With Toripalimab (Anti-PD-1 mAb) in Subjects With Advanced Solid Tumors
Scientific title
A Multicenter, Open-Label, Phase I/II Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of YH003 in Combination With Toripalimab (Anti-PD-1 mAb) in Subjects With Advanced Solid Tumors
Secondary ID [1] 0 0
YH003002
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - YH003
Treatment: Drugs - Toripalimab
Treatment: Drugs - Nab-paclitaxel
Treatment: Drugs - Gemcitabine

Experimental: YH003 with Toripalimab after PD-1/L1 +/- CTLA-4 treatment - YH003 in combination with Toripalimab in subjects with unresectable /metastatic melanoma after having failed PD-1/L1 +/- CTLA-4 treatment.

Experimental: YH003 with Toripalimab in subjects with PDAC - YH003 in combination with Toripalimab in subjects with unresectable/ metastatic pancreatic ductal adenocarcinoma (PDAC) as 2nd line treatment.

Experimental: YH003 with Toripalimab plus standard chemotherapy - YH003 in combination with Toripalimab plus standard chemotherapy (Nab-paclitaxel + Gemcitabine) in subjects with unresectable/metastatic PDAC as 1st line treatment


Treatment: Drugs: YH003
YH003 will be administered intravenously over 60 minutes every 21-day cycle.

Treatment: Drugs: Toripalimab
Toripalimab with fixed dose of 240 mg administered intravenously followed by YH003 administered intravenously every 21-day cycle.

Treatment: Drugs: Nab-paclitaxel
Nab-paclitaxel will be administered each 21-day cycle.

Treatment: Drugs: Gemcitabine
Gemcitabine will be administrated each 21-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall safety and tolerability profile of YH003 in combination with Toripalimab.
Timepoint [1] 0 0
From screening up to 1 year
Primary outcome [2] 0 0
Maximum tolerated dose (MTD) and Recommended phase 2 dose (RP2D)
Timepoint [2] 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 (AUC)
Timepoint [1] 0 0
Up to 1 year
Secondary outcome [2] 0 0
Maximum serum concentration (Cmax)
Timepoint [2] 0 0
Up to 1 year
Secondary outcome [3] 0 0
Trough concentration before the next dose is administered (Ctrough)
Timepoint [3] 0 0
Up to 1 year
Secondary outcome [4] 0 0
Time to reach maximum serum concentration (Tmax)
Timepoint [4] 0 0
Up to 1 year
Secondary outcome [5] 0 0
Clearance (CL)
Timepoint [5] 0 0
Up to 1 year
Secondary outcome [6] 0 0
Volume of distribution (Vd)
Timepoint [6] 0 0
Up to 1 year
Secondary outcome [7] 0 0
Volume of distribution at steady state (Vss)
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
1. Subjects must have the ability to understand and willingness to sign a written
informed consent document.

2. Part I dose escalation:

Have histologically advanced or cytologically confirmed solid tumor. Have progressed
on after treatment with at least one standard therapy or intolerant of the standard
therapy.

Part II dose expansion:

Cohort 2A: Histologically or cytologically confirmed unresectable or metastatic
melanoma that had confirmed progressive disease during treatment with an
anti-PD-1/PD-L1 therapy with or without additional CTLA-4 therapy. Subjects with BRAF
activating mutation could have also received a BRAF inhibitor and/or MEK inhibitor
regimen prior to anti-PD-1/PD-L1 therapy.

Cohort 2B, 2C: Subject has histologically or cytologically documented diagnosis of
pancreatic ductal adenocarcinoma with unresectable locally advanced/metastatic disease
Cohort 2B: had confirmed progressive disease during treatment with first line standard
of care of chemotherapy per local standard.

Cohort 2C: treatment-naïve for unresectable locally advanced/metastatic disease.

3. Subject must have measurable disease by RECIST 1.1. At least 1 unidimensional
measurable target lesion per RECIST v1.1 for study Part II expansion cohorts.

4. Subjects must be age 18 years or older.

5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 or 1. Life expectancy =3 months.

6. Subjects must have adequate organ function.

7. Women of reproductive potential must have negative serum beta human chorionic
gonadotropin (ß -HCG) pregnancy test.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Part II Cohort 2A: History of life-threatening toxicity or treatment discontinuation
due to related to prior anti-PD-1/PD-L1 and with or without CTLA-4 combination
treatment for subjects with unresectable/metastatic melanoma.

2. Subjects must not have another active invasive malignancy.

3. Previous exposure to TNFR such as anti-CD137, OX40, CD27 and CD357 antibodies.

4. Subjects must not have received any anticancer therapy or another investigational
agent within the shorter of 4 weeks or 5 half-lives before the first dose of the study
treatment.

5. Subjects with a history of = Grade 3 immune-related adverse events resulted from
previous immunotherapy.

6. History of clinically significant sensitivity or allergy to monoclonal antibodies and
their excipients or known allergies to antibodies produced from Chinese hamster ovary
cells, which in the opinion of the Investigator suggests an increased potential for an
adverse hypersensitivity to YH003 or Toripalimab. Also history of severe
hypersensitivity reaction to Nap-paclitaxel and/or gemcitabine.

7. Primary central nervous system (CNS) malignancies or symptomatic CNS metastases.

8. History of (non-infectious) pneumonitis that required corticosteroids or current
pneumonitis, or history of interstitial lung disease.

9. Subjects must not have a known or suspected history of an autoimmune disorder,
including but not limited to inflammatory bowel disease, celiac disease, Wegner
syndrome, Hashimoto syndrome, systemic lupus erythematosus, scleroderma, sarcoidosis,
or autoimmune hepatitis, within 3 years of the first dose of study treatment.

10. Clinically uncontrolled intercurrent illness, including an ongoing or active
infection, active coagulopathy, uncontrolled diabetes, psychiatric illness that would
limit compliance with the study requirements and other serious medical illnesses
requiring systemic therapies.

11. Severe cardiovascular disease including symptomatic congestive heart failure (New York
Heart Association class III or IV), unstable angina, uncontrolled hypertension,
cardiac arrhythmia, a history of myocardial infarction within 6 months or a history of
arterial thromboembolic event and pulmonary embolism within 3 months of the first dose
of investigational agent.

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

13. Subjects must not have active infection of human immunodeficiency virus (HIV),
hepatitis B, or hepatitis C.

14. Subjects must not have a history of primary immunodeficiency.

15. Subjects from endemic area will be specifically screened for tuberculosis. Subjects
with active tuberculosis are excluded.

16. Subjects must not receive concurrent or prior use of an immunosuppressive agent within
4 weeks of the first dose of YH003.

17. Major surgery within 4 weeks prior to study entry and Minor surgery within 2 weeks
prior to the first dose of YH003.

18. Subjects must not have received a live attenuated vaccine within 28 days before the
first dose of YH003, and subjects, if enrolled, should not receive live vaccines
during the study or for 180 days after the last dose of YH003.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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
Parallel
Other design features
Phase
Phase 1/Phase 2
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
4/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/05/2022
Sample size
Target
Accrual to date
Final
26
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
6009 - Nedlands

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 a phase I/II, multi-center, open-label study of YH003 in combination with Toripalimab
(anti-PD-1 mAb). The study is comprised of a dose escalation part (Part I) exploring
escalating doses of YH003 in combination with fixed dose toripalimab in subjects with
advanced solid tumors (Part I), followed by an expansion part (Part II) with three expansion
cohorts.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04481009
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/NCT04481009