A Study to Evaluate the Combination of YH003, YH001 and Pembrolizumab in Subjects With Advanced Solid Tumors

A Multicenter, Open-Label, Phase I Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of the Combination of YH003, YH001 and Pembrolizumab in Subjects With Advanced Solid Tumors

A Multicenter, Open-Label, Phase I Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of the Combination of YH003, YH001 and Pembrolizumab in Subjects with Advanced Solid Tumors

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: YH003; Drug: YH001; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Fangxia Pan; Phone Number: 86 010 85950770-8000; Email: fangxia.pan@eucure.com

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Recruiting
      • Blacktown Cancer and Haematology Centre, Clinical Trials, Block C, Level 3, 18 Blacktown Road
      • Contact: Amanda Bryant; Phone Number: 2867 05069; Email: Amanda.Bryant1@Health.nsw.gov.au
    • Kogarah, New South Wales, Australia, 2217
      • Recruiting
      • "Oncology Clinical Trial Unit St George Private Hospital 1 South Street"
      • Contact: Tracy Liaw; Phone Number: 2 8594 5785; Email: LiawT@ramsayhealth.com.au
  • Victoria
    • Melbourne, Victoria, Australia
      • Recruiting
      • 55 Commercial Rd, Level 2 WBRC
      • Contact: Nikki Cross; Phone Number: 390763534; Email: N.Cross@alfred.org.au
    • Prahran, Victoria, Australia
      • Recruiting
      • Level 3, Suite 7, North Building, Frankston Private, 5 Susono Way, Frankston
      • Contact: Albert Goikhman; Phone Number: 3 9113 1307; Email: ag@paso.com.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Subjects must have the ability to understand and willingness to sign a written informed consent document.
• 2. Subjects must have histologically advanced or cytologically confirmed solid tumor.
• 3. Subjects have progressed on after treatment with at least one standard therapy, or intolerant of the standard therapy, or no standard therapy accessible to the patients due to any reason
• 4. Subject must have at least 1 unidimensional measurable disease by RECIST 1.1(Eisenhauer et al., 2009).
• 5. Subjects must be age 18 years or older.
• 6. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 7. Life expectancy ≥3 months based on investigator's judgement.
• 8. Subjects must meet the following laboratory values at the screening
• 9. Women of reproductive potential must have negative serum beta human chorionic gonadotropin (β -HCG) pregnancy test within 7 days of the first dose of study drugs.
• 10. Women of reproductive potential who are sexually active with a non-sterilized male must consistently use highly effective contraception/birth control between signing of the informed consent and 120 days after the last administration of the study drugs.

Exclusion Criteria:

• 1. Subjects have another active invasive malignancy within 5 years
• 2. Subjects must not have received any anticancer therapy or another investigational agent within the longer of 4 weeks or 5 half-lives before the first dose of the study treatment
• 3. Subjects with a history of ≥ Grade 3 immune-related adverse events resulted from previous immunotherapy.
• 4. 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, YH001 or Pembrolizumab.
• 5. Primary central nervous system (CNS) malignancies or symptomatic CNS metastases.
• 6. History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis, or history of interstitial lung disease.
• 7. Subjects must not have a known or suspected history of an autoimmune disorder
• 8. Clinically uncontrolled intercurrent illness, including active coagulopathy, uncontrolled diabetes, psychiatric illness that would limit compliance with the study requirements and other serious medical illnesses requiring systemic therapies.
• 9. Has an active infection requiring systemic therapy.
• 10. Severe cardiovascular disease including symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina, uncontrolled hypertension, active coagulopathy, uncontrolled diabetes (blood glucose > 250 mg/dl), uncontrolled peritoneal effusion, 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.
• 11. QTcF> 480 ms at baseline; no concomitant medications that would prolong the QT interval; no family history of long QT syndrome.
• 12. Subjects must not have active infection of human immunodeficiency virus (HIV), hepatitis B, hepatitis C or Covid-19.
• 13. Subjects must not have a history of primary immunodeficiency.
• 14. Subjects from endemic area will be specifically screened for tuberculosis. Subjects with active tuberculosis are excluded. Subjects who have received BCG vaccination may have a false positive PPD test. These subjects are eligible if they have a negative Interferon Gamma Release Assay (IGRA).
• 15. Subjects must not receive concurrent or prior use of an immunosuppressive agent within 4 weeks of the first dose
• 16. Major surgery within 4 weeks prior to study entry and Minor surgery within 2 weeks prior to the first dose.
• 17. Subjects must not have received any vaccine within 28 days before the first dose, and subjects, if enrolled, should not receive live vaccines during the study or for 180 days after the last dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention/treatment	Drug: YH003; YH003 will be administered intravenously over 60 minutes every 21-day cycle.; Drug: YH001; YH001 will be administered intravenously over 60 minutes every 21-day cycle.; Drug: Pembrolizumab; Pembrolizumab will be administered intravenously over 30 minutes every 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	The safety will be assessed by monitoring the adverse events (AE) per NCI CTCAE v5.0	up to 1 year after the last dosing
Maximum tolerated dose (MTD) and/or Recommended phase 2 dose (RP2D)	The MTD and/or RP2D will be determined based on the data of safety and tolerability	up to 1 year after the last dosing

Collaborators and Investigators

• Sponsor: Eucure (Beijing) Biopharma Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2022
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 15, 2021
• First Submitted That Met QC Criteria: December 15, 2021
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: YH003005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No