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A Study to Evaluate YH001 in Combination With Toripalimab in Subjects With Advanced NSCLC and HCC (YH001)

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ClinicalTrials.gov Identifier: NCT05212922
Recruitment Status : Not yet recruiting
First Posted : January 28, 2022
Last Update Posted : July 22, 2022
Sponsor:
Information provided by (Responsible Party):
Eucure (Beijing) Biopharma Co., Ltd

Study Description
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Brief Summary:
This is an Open-label, Non-Randomized, Multi-center Phase 2 study of YH001 in Combination with Toripalimab，The study is designed to determine the safety ，tolerability and antitumor activity of YH001 in combination with Toripalimab in subjects with advanced NSCLC and HCC.

Condition or disease Intervention/treatment Phase
HCC NSCLC Stage IIIB NSCLC Stage IV Drug: YH001 + Toripalimab Phase 2

Detailed Description:

This study will include two cohorts of up to 40 subjects each treated with RP2D dose YH001 in combination with 240 mg Toripalimab to assess the antitumor activity and safety/tolerability.

According to Simon's two stage design, in the first stage, 9-10 subjects will be accrued. If there are ≤ 1 subjects achieving an objective response, the futility stop will be called. Enrollment will start for the second stage after Stage 1 data pass futility test. In the second stage, 17-19subjects will be enrolled to have 27 subjects in total. If there are ≥ 5 subjects achieving an objective response, a stop could be called for meeting the primary objective.

In all cohorts, 4 mg/kg or other higher dose level of YH001 (not exceeding MTD) may be needed based on the safety data in the first stage.

  • Cohort A: YH001 in combination with Toripalimab in subjects with advanced PD-L1 positive NSCLC as 1st line treatment;
  • Cohort B: YH001 in combination with Toripalimab in subjects with previously systemically treated advanced HCC as 2nd line treatment;
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single Group Assignmen
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Non-Randomized, Multi-center Phase 2 Study of YH001 in Combination With Toripalimab in Subjects With Advanced Non-small Cell Lung Cancer (NSCLC) and Hepatocellular Carcinoma (HCC)
Estimated Study Start Date : December 2022
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: YH001 + Toripalimab
This study will include two cohorts of up to 40 subjects each treated with RP2D dose of YH001 in combination with 240 mg Toripalimab to assess the antitumor activity and safety/tolerability.
 Drug: YH001 + Toripalimab
YH001 + Toripalimab


Outcome Measures
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Primary Outcome Measures :
  1. ORR [ Time Frame: maximum of 1 years after the first dose of YH001 and Toripalimab study treatment. ]
    Overall Response Rate (ORR) by investigator's assessment according to the RECIST v1.1


Secondary Outcome Measures :
  1. safety and tolerability [ Time Frame: maximum of 1 years after the first dose of YH001 and Toripalimab study treatment. ]
    The safety and tolerability will be assessed by monitoring the adverse events (AE) per NCI CTCAE v5.0

  2. OS [ Time Frame: maximum of 1 years after the first dose of YH001 and Toripalimab study treatment. ]
    To assess other antitumor activity of YH001 in combination with Toripalimab

  3. anti-drug antibodies (ADA) [ Time Frame: maximum of 1 years after the first dose of YH001 and Toripalimab study treatment. ]
    Immunogenicity

  4. neutralizing antibodies (NAbs). [ Time Frame: maximum of 1 years after the first dose of YH001 and Toripalimab study treatment. ]
    To assess the immunogenicity of YH001 in combination with Toripalimab

  5. peak concentration (Cmax) [ Time Frame: maximum of 1 years after the first dose of YH001 and Toripalimab study treatment. ]
    To characterize the pharmacokinetic (PK) profiles of YH001 in combination with Toripalimab


Other Outcome Measures:
  1. trough concentration (Ctrough) [ Time Frame: maximum of 1 years after the first dose of YH001 and Toripalimab study treatment. ]
    To characterize the pharmacokinetic (PK) profiles of YH001 in combination with Toripalimab

  2. terminal half-life (T1/2). [ Time Frame: maximum of 1 years after the first dose of YH001 and Toripalimab study treatment. ]
    To characterize the pharmacokinetic (PK) profiles of YH001 in combination with Toripalimab

  3. Duration of response (DOR) [ Time Frame: maximum of 1 years after the first dose of YH001 and Toripalimab study treatment. ]
    To assess other antitumor activity of YH001 in combination with Toripalimab by investigator's assessment according to the RECIST v1.1

  4. progression free survival (PFS) [ Time Frame: maximum of 1 years after the first dose of YH001 and Toripalimab study treatment. ]
    To assess other antitumor activity of YH001 in combination with Toripalimab by investigator's assessment according to the RECIST v1.1

  5. time to response (TTR) [ Time Frame: maximum of 1 years after the first dose of YH001 and Toripalimab study treatment. ]
    To assess other antitumor activity of YH001 in combination with Toripalimab by investigator's assessment according to the RECIST v1.1


Eligibility Criteria
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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:

  1. Male or female, aged ≥ 18 years；
  2. Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures.

  3. Target Population

    Cohort A:

    • Have histologically or cytologically confirmed diagnosis of NSCLC (squamous or non-squamous)
    • Recurrent or unresectable locally advanced (Stage IIIB) or metastatic (Stage IV);
    • Naïve to any systemic anti-cancer therapy
    • No EGFR mutation or ALK/ ROS1 gene rearrangement
    • PD-L1 positive (TPS≥1%) NSCLC

    Cohort B:

    • HCC diagnosis confirmed by or radiology, histology, or cytology;
    • Barcelona Clinic Liver Cancer (BCLC) Stage C or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy and not amenable to a curative treatment approach;
    • Child-Pugh A liver score within 7 days prior to first dose of study drug;
    • Documented objective radiographic progression during or after treatment with sorafenib/lenvatinib, or intolerant of sorafenib/lenvatinib; or documented objective radiographic progression during or after treatment with atezolizumab and bevacizumab, or intolerant of atezolizumab and bevacizumab.
  4. At least 1 unidimensional measurable target lesion per RECIST v1.1
  5. ECOG performance status score 0 or 1
  6. Have life expectancy of at least 12 weeks based on investigator's judgement.
  7. Adequate organ and bone marrow function:
  8. Women of reproductive potential must have negative serum beta human chorionic gonadotropin (β -HCG) pregnancy test within 7 days of the fist dose of YH001.
  9. 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 drug.

Exclusion Criteria:

  1. Treatment with any investigational drug within 4 weeks prior to the fist dose of study drug；

  2. Prior anticancer therapy:

    • Cohort B: Subjects received sorafenib/lenvatinib within 14 days of first dose of study medication.
    • Prior palliative radiotherapy to bone metastases ≤ 2 weeks prior to the first dose of YH001 is acceptable.
    • It is unacceptable to have wash out less than 2 weeks for herbal therapy approved for anticancer.
  3. Subjects with prior anti-CTLA-4 checkpoint inhibitors should be excluded.
  4. Subjects with a history of ≥ Grade 3 immune-related adverse events resulted from previous immunotherapy or an AE of any grade that resulted in discontinuation of prior immunotherapy
  5. History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis, or history of interstitial lung disease
  6. 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
  7. Allergic to YH001 and Toripalimab or any component of the study drug formulation.
  8. 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.
  9. Primary central nervous system (CNS) malignancies or symptomatic CNS metastases.
  10. Subjects with severe cardiovascular diseases, e.g. New York Heart Association (NYHA) Class III or IV heart failure, myocardial infection within 6 months prior to first dose of YH001, uncontrolled hypertension, unstable angina pectoris or unstable cardiac arrhythmia.
  11. QTcF > 470 ms at baseline; no concomitant medications that would prolong the QT interval; no family history of long QT syndrome.

  12. Viral infection:

    • Acute or Chronic active Hepatitis B (HBsAg positive and HBV DNA≥2000 IU/mL).
    • Chronic HCV infection (HCV antibody positive and HCV RNA detectable).
    • Human immunodeficiency virus (HIV) infection as well as COVID-19.
  13. 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).
  14. Clinically uncontrolled concurrent illnesses, including, but not limited to, active infection that requires systematic treatment, serious diabetes (fasting blood glucose > 250 mg/dl), psychiatric illness that would limit compliance with the study requirements and other serious medical illnesses requiring systemic therapies.
  15. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have not recovered to ≤ Grade 1 per CTCAE v5.0
  16. Failure to recover adequately, as judged by the investigator, from prior surgical procedures; the subjects have had major surgery within 28 days, or minor surgery within 2 weeks prior to the first dose of YH001.
  17. Subjects received any live or attenuated vaccine within 28 days prior to the first dosing of study drug. For inactivated or attenuated COVID -19 vaccine, follow local guidelines.
  18. Pregnant or breast-feeding females.
  19. Any clinically significant abnormality in the laboratory
  20. Subjects have another active invasive malignancy within 5 years

  21. Cohort B:

    • History of esophageal or gastric variceal bleeding within the last 6 months, or current active gastrointestinal bleeding;
    • Large tumor lesion in liver (≥60% liver volum), portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging;
    • Clinically diagnosed hepatic encephalopathy in the last 6 months
Contacts and Locations
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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): NCT05212922


Contacts
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Contact: Fangxia Pan +86 01085950770 ext 8005 fangxia.pan@eucure.com

Locations
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Sponsors and Collaborators
Eucure (Beijing) Biopharma Co., Ltd
Investigators
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Study Chair: Rong Chen, Ph.D Eucure (Beijing) Biopharma Co., Ltd
More Information
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Responsible Party: Eucure (Beijing) Biopharma Co., Ltd
ClinicalTrials.gov Identifier: NCT05212922    
Other Study ID Numbers: YH001004
First Posted: January 28, 2022    Key Record Dates
Last Update Posted: July 22, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
 Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases