A Study of SHR-1501 Combined With SHR-1316 in Patients With Advanced Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Malignancies
• Intervention / Treatment: Drug: SHR-1501; Drug: SHR-1316

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Sydney Southwest Private Hospital
    • Randwick, New South Wales, Australia, 2031
      • Scientia Clinical Research
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Centre South Brisbane
    • Tugun, Queensland, Australia, 4224
      • John Flynn Private Hospital
• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital & Guangdong Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 18-75 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. FFPE tumor tissue or unstained slides of tumor sample must be obtained from patients enrolled in the dose expansion or indication expansion stage, both preserved samples collected within 6 months before the first dose (or up to 12 months prior to the first dose) and fresh samples (preferred) are acceptable;
7. Eastern Cooperative Oncology Group ECOG PS score of 0-1;
8. Have a life expectancy of ≥ 12 weeks;
9. Adequate organ function defined according to the protocol, These results should be completed within 14 days prior to the first study treatment:
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity and Maximum tolerated dose	Dose-limiting toxicity and Maximum tolerated dose in patients with advanced tumors treated by SHR-1501 combined with SHR-1316.	Approximately 42 Days.
Recommended Phase 2 dose (RP2D)	Recommended Phase 2 dose (RP2D) based on comprehensive evaluation	Approximately 2 years
Adverse event/Serious adverse event	Incidence/severity of adverse events/serious adverse events (rated based on CTC AE v5.0)	Approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK)	Single dose: maximum concentration (Cmax)	Approximately 2 years
Pharmacokinetic (PK)	Single dose: time to maximum concentration (Tmax)	Approximately 2 years
Pharmacokinetic (PK)	Single dose: areas under the concentration-time curve (AUClast and AUCinf)	Approximately 2 years
Pharmacokinetic (PK)	Single dose: half-life (t1/2)	Approximately 2 years
Pharmacokinetic (PK)	Single dose: clearance (CL)	Approximately 2 years
Pharmacokinetic (PK)	Single dose: mean residence time (MRT)	Approximately 2 years
Pharmacokinetic (PK)	Single dose: volume at steady state (Vss)	Approximately 2 years
Pharmacokinetic (PK)	Multiple doses (at steady state, if applicable): maximum concentration at steady state （Css_max）	Approximately 2 years
Pharmacokinetic (PK)	Multiple doses (at steady state, if applicable): time to maximum concentration （Tss_max）	Approximately 2 years
Pharmacokinetic (PK)	Multiple doses (at steady state, if applicable): area under the concentration-time curve at steady state （AUCss）	Approximately 2 years
Pharmacokinetic (PK)	Multiple doses (at steady state, if applicable): t1/2	Approximately 2 years
Pharmacokinetic (PK)	Multiple doses (at steady state, if applicable):steady-state minimum concentration at steady state （Css_min）	Approximately 2 years
Pharmacokinetic (PK)	Multiple doses (at steady state, if applicable): average concentration at steady state（Css_av）	Approximately 2 years
Pharmacokinetic (PK)	Multiple doses (at steady state, if applicable): accumulation ratio （Rac）	Approximately 2 years
Immune related features	indicated by the count of CD8+ T-lymphocytes in peripheral blood at scheduled post-dose time points.	Approximately 2 years
Immune related features	indicated by the percentage of CD8+ T-lymphocytes in peripheral blood at scheduled post-dose time points.	Approximately 2 years
Immune related features	indicated by the count of natural killer (NK) cells in peripheral blood at scheduled post-dose time points.	Approximately 2 years
Immune related features	indicated by the percentage of natural killer (NK) cells in peripheral blood at scheduled post-dose time points.	Approximately 2 years
Objective response rate	Percentage of participants with CR or PR.	Approximately 2 years
Disease control rate	Percentage of participants with CR or PR or SD.	Approximately 2 years
Duration of response	Duration of time of tumor remission.	Approximately 2 years
progression-free survival	Progression-free survival time.	Approximately 2 years
12 months overall survival	12-month survival rate.	Approximately 2 years
Durable clinical benefit rate at 6 month	Percentage of participants with CR or PR or SD lasts over six months.	Approximately 2 years
Immunogenicity	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.	Approximately 2 years

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Study Director: Yilong Wu, MD, Guangdong General Hospital & Guangdong Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2020
• Primary Completion (Actual): January 12, 2023
• Study Completion (Actual): January 12, 2023

Study Registration Dates

• First Submitted: May 9, 2019
• First Submitted That Met QC Criteria: June 21, 2019
• First Posted (Actual): June 24, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SHR-1501-I-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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