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

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ClinicalTrials.gov Identifier: NCT04353102
Recruitment Status : Completed
First Posted : April 20, 2020
Last Update Posted : July 22, 2022
Sponsor:
Information provided by (Responsible Party):
Eucure (Beijing) Biopharma Co., Ltd

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).

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Study Type : Interventional  (Clinical Trial)
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 : April 22, 2020
Actual Primary Completion Date : September 14, 2021
Actual Study Completion Date : November 24, 2021

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.




Primary Outcome Measures :
  1. Number of participants with adverse events and serious adverse events [ Time Frame: 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

  2. Maximum tolerated dose (MTD) [ Time Frame: 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

  3. Dose-limiting toxicities (DLT) [ Time Frame: 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 :
  1. Area under the serum concentration versus time curve within one dosing interval (AUCtau) [ Time Frame: Up to 2 years ]
    To determine the pharmacokinetics (PK) profile of YH002

  2. Volume of distribution (Vd) [ Time Frame: Up to 2 years ]
    To determine the pharmacokinetics (PK) profile of YH002

  3. Volume of distribution at steady state (Vss) [ Time Frame: Up to 2 years ]
    To determine the pharmacokinetics (PK) profile of YH002

  4. Maximum serum concentration (Cmax) [ Time Frame: Up to 2 years ]
    To determine the PK profile of YH002 as single agent

  5. Trough concentration before the next dose is administered (Ctrough) [ Time Frame: Up to 2 years ]
    To determine the PK profile of YH002

  6. Time to reach maximum serum concentration (Tmax) [ Time Frame: Up to 2 years ]
    To determine the PK profile of YH002

  7. Clearance (CL) [ Time Frame: Up to 2 years ]
    To determine the PK profile of YH002

  8. Terminal half-life (T1/2) [ Time Frame: Up to 2 years ]
    To determine the PK profile of YH002

  9. Dose proportionality [ Time Frame: Up to 2 years ]
    To determine the PK profile of YH002

  10. Incidence of anti-drug antibodies (ADAs) [ Time Frame: Up to 2 years ]
    To assess the immunogenicity of YH002

  11. Incidence of neutralizing antibodies (NAbs) [ Time Frame: Up to 2 years ]
    To assess the immunogenicity of YH002

  12. Objective response rate (ORR) [ Time Frame: Up to 2 years ]
    To assess the preliminary antitumor activity of YH002

  13. Duration of response (DOR) [ Time Frame: Up to 2 years ]
    To assess the preliminary antitumor activity of YH002

  14. Progression free survival (PFS) [ Time Frame: Up to 2 years ]
    To assess the preliminary antitumor activity of YH002

  15. Time to response (TTR) [ Time Frame: Up to 2 years ]
    To assess the preliminary antitumor activity of YH002

  16. Disease control rate (DCR) [ Time Frame: Up to 2 years ]
    To assess the preliminary antitumor activity of YH002

  17. Duration of disease control (DOC) [ Time Frame: Up to 2 years ]
    To assess the preliminary antitumor activity of YH002



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04353102


Locations
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Australia, New South Wales
St George Private Hospital
Kogarah, New South Wales, Australia, 2217
Macquarie University
Macquarie, New South Wales, Australia, 2162
Australia, Victoria
Peninsula & South Eastern Haematology and Oncology Group
Frankston, Victoria, Australia, 3199
Sponsors and Collaborators
Eucure (Beijing) Biopharma Co., Ltd
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Responsible Party: Eucure (Beijing) Biopharma Co., Ltd
ClinicalTrials.gov Identifier: NCT04353102    
Other Study ID Numbers: YH002002
First Posted: April 20, 2020    Key Record Dates
Last Update Posted: July 22, 2022
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eucure (Beijing) Biopharma Co., Ltd:
dose escalation
safety
tolerability
advanced solid malignancie
pharmacokinetics
Additional relevant MeSH terms:
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Neoplasms