Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Assess YH001 in Combination With Toripalimab Injection in Subjects With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04357756
Recruitment Status : Not yet recruiting
First Posted : April 22, 2020
Last Update Posted : April 22, 2020
Sponsor:
Information provided by (Responsible Party):
Eucure (Beijing) Biopharma Co., Ltd

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: YH001 Drug: Toripalimab Phase 1

Detailed Description:

This trial will have a run-in phase to explore the safety and tolerability of YH001 as a single agent for 21 days as DLT observation period then followed by a combination phase to further explore the safety and tolerability of YH001 combined with Toripalimab (anti-PD-1 antibody) for each dose level during dose escalation.

The dose escalation will follow the traditional "3 + 3" dose escalation scheme. These subjects will be treated with YH001 and Toripalimab. 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. Toripalimab will be administered by IV (Q3W) by the fixed dose of 240 mg from the 2nd cycle to 5th cycle. A single subject will be enrolled at Dose A as starting dose of YH001, and subsequent cohort will be expanded to include 3-6 subjects.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Estimated Study Start Date : April 21, 2020
Estimated Primary Completion Date : March 29, 2021
Estimated Study Completion Date : February 14, 2022

Arm Intervention/treatment
Experimental: YH001 combined with Toripalimab
All the patients will receive YH001 intravenously as single agent for 21 days followed by combination phase.
Drug: 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.

Drug: Toripalimab
Toripalimab will be administered by intravenously (Q3W) by the fixed dose of 240 mg from the 2nd cycle to 5th cycle.




Primary Outcome Measures :
  1. Number of participants with adverse events and serious adverse events [ Time Frame: From screening up to 1 year ]
    The safety profile of YH001 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: During Cycle 1 (each cycle is 21 days) ]
    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: During Cycle 1 (each cycle is 21 days) ]
    DLT is defined as a toxicity (adverse event at least possibly related to YH001) occurring during the DLT observation period (the initial 21 days) both in run-in phase of YH001 as single agent and in combination phase of YH001 in combination with Toripalimab


Secondary Outcome Measures :
  1. Area under the serum concentration versus time curve within one dosing interval (AUCtau) [ Time Frame: Up to 1 year ]
    To determine the PK profile of YH001 alone and in combination with Toripalimab

  2. Steady state AUC [ Time Frame: Up to 1 year ]
    To determine the PK profile of YH001 alone and in combination with Toripalimab

  3. Maximum serum concentration (Cmax) [ Time Frame: Up to 1 year ]
    To determine the PK profile of YH001 alone and in combination with Toripalimab

  4. Trough concentration before the next dose is administered (Ctrough) [ Time Frame: Up to 1 year ]
    To determine the PK profile of YH001 alone and in combination with Toripalimab

  5. Time to reach maximum serum concentration (Tmax) [ Time Frame: Up to 1 year ]
    To determine the PK profile of YH001 alone and in combination with Toripalimab

  6. Clearance (CL) [ Time Frame: Up to 1 year ]
    To determine the PK profile of YH001 alone and in combination with Toripalimab

  7. Volume of distribution (Vd) [ Time Frame: Up to 1 year ]
    To determine the PK profile of YH001 alone and in combination with Toripalimab

  8. Terminal half-life (T1/2) [ Time Frame: Up to 1 year ]
    To determine the PK profile of YH001 alone and in combination with Toripalimab

  9. Dose proportionality [ Time Frame: Up to 1 year ]
    To determine the PK profile of YH001 alone and in combination with Toripalimab

  10. Incidence of anti-drug antibodies (ADAs) [ Time Frame: Up to 1 year ]
    To assess the immunogenicity of YH001 in combination with Toripalimab

  11. Incidence of neutralizing antibodies (NAbs) [ Time Frame: Up to 1 year ]
    To assess the immunogenicity of YH001 in combination with Toripalimab

  12. Objective response rate (ORR) [ Time Frame: Up to 1 year ]
    To assess the preliminary antitumor activity of YH001 in combination with Toripalimab

  13. Duration of response (DOR) [ Time Frame: Up to 1 year ]
    To assess the preliminary antitumor activity of YH001 in combination with Toripalimab

  14. Time to response (TTR) [ Time Frame: Up to 1 year ]
    To assess the preliminary antitumor activity of YH001 in combination with Toripalimab

  15. Progression free survival (PFS) [ Time Frame: Up to 1 year ]
    To assess the preliminary antitumor activity of YH001 in combination with Toripalimab

  16. Overall survival (OS) [ Time Frame: Up to 1 year ]
    To assess the preliminary antitumor activity of YH001 in combination with Toripalimab

  17. Disease control rate (DCR) [ Time Frame: Up to 1 year ]
    To assess the preliminary antitumor activity of YH001 in combination with Toripalimab

  18. Duration of disease control (DDC) [ Time Frame: Up to 1 year ]
    To assess the preliminary antitumor activity of YH001 in combination with Toripalimab



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.


Layout table for eligibility information
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
  • 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

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

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): NCT04357756


Contacts
Layout table for location contacts
Contact: Ryan Wen ryan.wen@eucure.com

Sponsors and Collaborators
Eucure (Beijing) Biopharma Co., Ltd
Layout table for additonal information
Responsible Party: Eucure (Beijing) Biopharma Co., Ltd
ClinicalTrials.gov Identifier: NCT04357756    
Other Study ID Numbers: YH001002
First Posted: April 22, 2020    Key Record Dates
Last Update Posted: April 22, 2020
Last Verified: April 2020

Layout table for additional information
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 tumors
pharmacokinetics
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms