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History of Changes for Study: NCT03995472
A Study of SHR-1501 Combined With SHR-1316 in Patients With Advanced Tumors
Latest version (submitted September 26, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 21, 2019 None (earliest Version on record)
2 January 12, 2020 Study Status, Contacts/Locations, Study Design and Oversight
3 January 13, 2020 Study Status and Contacts/Locations
4 February 7, 2020 Study Status and Oversight
5 February 11, 2020 Eligibility, Contacts/Locations and Study Status
6 February 17, 2020 Recruitment Status, Study Status and Contacts/Locations
7 July 21, 2020 Contacts/Locations and Study Status
8 July 13, 2022 Recruitment Status, Study Status, Contacts/Locations, Study Design and IPDSharing
9 December 19, 2022 Study Status
10 September 26, 2023 Recruitment Status and Study Status
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Study NCT03995472
Submitted Date:  February 7, 2020 (v4)

Open or close this module Study Identification
Unique Protocol ID: SHR-1501-I-101
Brief Title: A Study of SHR-1501 Combined With SHR-1316 in Patients With Advanced Tumors
Official Title: A Phase I Clinical Study to Evaluate the Tolerability, Safety, Pharmacokinetics and Efficacy of SHR-1501 in Combination With SHR-1316 in Patients With Advanced Malignancies
Secondary IDs:
Open or close this module Study Status
Record Verification: February 2020
Overall Status: Not yet recruiting
Study Start: February 2020
Primary Completion: June 2022 [Anticipated]
Study Completion: June 2023 [Anticipated]
First Submitted: May 9, 2019
First Submitted that
Met QC Criteria:
June 21, 2019
First Posted: June 24, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
February 7, 2020
Last Update Posted: February 11, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Jiangsu HengRui Medicine Co., Ltd.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: The purpose of this study is to evaluate the safety and tolerability of SHR-1501 in combination with SHR-1316 in patients with advanced malignancies and to provide a recommended dose (RP2D) for subsequent clinical studies.
Detailed Description:
Open or close this module Conditions
Conditions: Advanced Malignancies
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Sequential Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 104 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: SHR-1501 and SHR-1316 dose escalation
SHR-1501 given subcutaneously with different doses. SHR-1316 given intravenously.
Drug: SHR-1501
Administered subcutaneously
Drug: SHR-1316
Administered intravenously
Experimental: SHR-1501 and SHR-1316 dose expansion
SHR-1501 given subcutaneously with different doses. SHR-1316 given intravenously.
Drug: SHR-1501
Administered subcutaneously
Drug: SHR-1316
Administered intravenously
Experimental: SHR-1501 and SHR-1316 Indication expansion
SHR-1501 given subcutaneously with a recommended dose. SHR-1316 given intravenously.
Drug: SHR-1501
Administered subcutaneously
Drug: SHR-1316
Administered intravenously
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Dose-limiting toxicity and Maximum tolerated dose
[ Time Frame: Approximately 42 Days. ]

Dose-limiting toxicity and Maximum tolerated dose in patients with advanced tumors treated by SHR-1501 combined with SHR-1316.
2. Recommended Phase 2 dose (RP2D)
[ Time Frame: Approximately 2 years ]

Recommended Phase 2 dose (RP2D) based on comprehensive evaluation
3. Adverse event/Serious adverse event
[ Time Frame: Approximately 2 years ]

Incidence/severity of adverse events/serious adverse events (rated based on CTC AE v5.0)
Secondary Outcome Measures:
1. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Single dose: maximum concentration (Cmax)
2. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Single dose: time to maximum concentration (Tmax)
3. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Single dose: areas under the concentration-time curve (AUClast and AUCinf)
4. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Single dose: half-life (t1/2)
5. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Single dose: clearance (CL)
6. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Single dose: mean residence time (MRT)
7. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Single dose: volume at steady state (Vss)
8. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Multiple doses (at steady state, if applicable): maximum concentration at steady state (Css_max)
9. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Multiple doses (at steady state, if applicable): time to maximum concentration (Tss_max)
10. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Multiple doses (at steady state, if applicable): area under the concentration-time curve at steady state (AUCss)
11. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Multiple doses (at steady state, if applicable): t1/2
12. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Multiple doses (at steady state, if applicable):steady-state minimum concentration at steady state (Css_min)
13. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Multiple doses (at steady state, if applicable): average concentration at steady state(Css_av)
14. Pharmacokinetic (PK)
[ Time Frame: Approximately 2 years ]

Multiple doses (at steady state, if applicable): accumulation ratio (Rac)
15. Immune related features
[ Time Frame: Approximately 2 years ]

indicated by the count of CD8+ T-lymphocytes in peripheral blood at scheduled post-dose time points.
16. Immune related features
[ Time Frame: Approximately 2 years ]

indicated by the percentage of CD8+ T-lymphocytes in peripheral blood at scheduled post-dose time points.
17. Immune related features
[ Time Frame: Approximately 2 years ]

indicated by the count of natural killer (NK) cells in peripheral blood at scheduled post-dose time points.
18. Immune related features
[ Time Frame: Approximately 2 years ]

indicated by the percentage of natural killer (NK) cells in peripheral blood at scheduled post-dose time points.
19. Objective response rate
[ Time Frame: Approximately 2 years ]

Percentage of participants with CR or PR.
20. Disease control rate
[ Time Frame: Approximately 2 years ]

Percentage of participants with CR or PR or SD.
21. Duration of response
[ Time Frame: Approximately 2 years ]

Duration of time of tumor remission.
22. progression-free survival
[ Time Frame: Approximately 2 years ]

Progression-free survival time.
23. 12 months overall survival
[ Time Frame: Approximately 2 years ]

12-month survival rate.
24. Durable clinical benefit rate at 6 month
[ Time Frame: Approximately 2 years ]

Percentage of participants with CR or PR or SD lasts over six months.
25. Immunogenicity
[ Time Frame: Approximately 2 years ]

The immunogenicity of SHR-1501 single drug and the immunogenicity of SHR-1316 combined with SHR-1501. The indicator includes number of participants with anti-drug antibody positive or neutralizing antibody positive.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 70 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

• All Patients All patients must meet all the following criteria to be eligible to participate:

  1. Voluntarily participate in this clinical study, understand the research procedure and be able to sign informed consent in writing;
  2. Subjects must be willing and able to follow the research protocol;
  3. Aged 18-70 years old when the informed consent form is signed;
  4. Have a histologically or cytologically confirmed diagnosis of advanced or metastatic tumor malignancy;
  5. Patients' malignancies must be relapsed or refractory to standard treatment, or patients cannot tolerate standard treatment, or patients have actively refused standard therapy;
  6. Eastern Cooperative Oncology Group ECOG PS score of 0-1;
  7. Have a life expectancy of ≥ 12 weeks;
  8. Adequate organ function defined according to the protocol, These results should be completed within 14 days prior to the first study treatment:
  9. Non-surgically sterilized women of childbearing age or male subjects are required to consent to the use of at least one medically approved contraceptive (eg intrauterine devices, contraceptives or condoms) is performed during the study treatment period and within 3 months of the end of the study treatment period.

Exclusion Criteria:

  1. Patients with cancerous meningitis (ie meningeal metastasis);
  2. Patients with active central nervous system (CNS) metastasis.
  3. Spinal cord compression that cannot be radically treated with surgery and/or radiotherapy cannot be enrolled.
  4. Patients with double cancer or more serious cancer;
  5. Patients with a history of autoimmune diseases;
  6. Significant clinical significance in the history of cardiovascular disease;
  7. Arterial/venous thrombosis events such as cerebrovascular accidents deep vein thrombosis and pulmonary embolism within 6 months prior to first administration;
  8. Have a history of immunodeficiency including HIV infection;
  9. Active hepatitis B or hepatitis C patients;
  10. Any disease or symptom that is not appropriate for inclusion in this study determined by the investigator.;
  11. Patients have undergone major surgery within 28 days prior to the first dose (except for diagnostics);
  12. Those who used a live attenuated vaccine within 4 weeks prior to the first dose or expect a live attenuated vaccine during the study period;
  13. Those who received other clinical trials within 4 weeks prior to the first study;
  14. Those who received systemic immunosuppressive therapy within 2 weeks prior to the first study dose;
  15. Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation;
  16. A history of severe allergic reactions to other monoclonal antibody/fusion protein drugs;
  17. Mental illness, alcohol abuse, drug abuse or substance abuse;
  18. Any disease or condition that causes reasonable suspicion to prohibit the use of the study drug or affect the interpretation of the study results or the patient is at high risk of treatment complications (any other disease, metabolic disorder, physical examination results or laboratory tests abnormalities);
  19. Pregnant or lactating women or women planning to become pregnant during the study.
Open or close this module Contacts/Locations
Central Contact Person: Jianjun Zou, MD
Telephone: 021-68868570
Email: zoujianjun@hrglobe.cn
Central Contact Backup: Wei Shi, MD
Telephone: 021-68868570
Email: shiwei@hrglobe.cn
Study Officials: Yilong Wu, MD
Study Director
Guangdong General Hospital & Guangdong Academy of Medical Sciences
Locations: Australia, New South Wales
Sydney Southwest Private Hospital
Liverpool, New South Wales, Australia, 2170
Contact:Contact: Aflah Roohullah 87389744 Aflah.Roohullah@health.nsw.gov.au
Australia, Queensland
Icon Cancer Centre South Brisbane
South Brisbane, Queensland, Australia, 4101
Contact:Contact: Jermaine Coward 37374500 jim.coward@iconcancercare.com.au
John Flynn Private Hospital
Tugun, Queensland, Australia, 4224
Contact:Contact: Andrea Tazbirkova 55314811 tazbirkova@yahoo.com.au
China, Guangdong
Guangdong General Hospital & Guangdong Academy of Medical Sciences
Guangzhou, Guangdong, China, 510080
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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