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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Malignancies

Intervention / Treatment
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* Drug: SHR-1501
* Drug: SHR-1316


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • All Patients All patients must meet all the following criteria to be eligible to participate: Voluntarily participate in this clinical study, understand the research procedure and be able to sign informed consent in writing; Subjects must be willing and able to follow the research protocol; Aged 18-75 years old when the informed consent form is signed; Have a histologically or cytologically confirmed diagnosis of advanced or metastatic tumor malignancy; Patients' malignancies must be relapsed or refractory to standard treatment, or patients cannot tolerate standard treatment, or patients have actively refused standard therapy; 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; Eastern Cooperative Oncology Group ECOG PS score of 0-1; Have a life expectancy of ≥ 12 weeks; Adequate organ function defined according to the protocol, These results should be completed within 14 days prior to the first study treatment: 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: Patients with cancerous meningitis (ie meningeal metastasis); Patients with active central nervous system (CNS) metastasis. Spinal cord compression that cannot be radically treated with surgery and/or radiotherapy cannot be enrolled. Patients with double cancer or more serious cancer; Patients with a history of autoimmune diseases; Significant clinical significance in the history of cardiovascular disease; Arterial/venous thrombosis events such as cerebrovascular accidents deep vein thrombosis and pulmonary embolism within 6 months prior to first administration; Have a history of immunodeficiency including HIV infection; Active hepatitis B or hepatitis C patients; Any disease or symptom that is not appropriate for inclusion in this study determined by the investigator.; Patients have undergone major surgery within 28 days prior to the first dose (except for diagnostics); 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; Those who received other clinical trials within 4 weeks prior to the first study; Those who received systemic immunosuppressive therapy within 2 weeks prior to the first study dose; Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation; A history of severe allergic reactions to other monoclonal antibody/fusion protein drugs; Mental illness, alcohol abuse, drug abuse or substance abuse; 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); Pregnant or lactating women or women planning to become pregnant during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1501 and SHR-1316 dose escalation<br>SHR-1501 given subcutaneously with different doses. SHR-1316 given intravenously. | Drug: SHR-1501<br>* Administered subcutaneously<br>Drug: SHR-1316<br>* Administered intravenously<br>|
| Experimental: SHR-1501 and SHR-1316 dose expansion<br>SHR-1501 given subcutaneously with different doses. SHR-1316 given intravenously. | Drug: SHR-1501<br>* Administered subcutaneously<br>Drug: SHR-1316<br>* Administered intravenously<br>|
| Experimental: SHR-1501 and SHR-1316 Indication expansion<br>SHR-1501 given subcutaneously with a recommended dose. SHR-1316 given intravenously. | Drug: SHR-1501<br>* Administered subcutaneously<br>Drug: SHR-1316<br>* Administered intravenously<br>|

What is the study measuring?
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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 |