An Open Phase I Clinical Trial of SHR-1826 for Injection in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is an open, multi-center, dose-escalation/dose-expansion/efficacy expansion phase I clinical study to evaluate the tolerability, safety, PK, and immunogenicity of SHR-1826 in patients with advanced malignant solid tumors, and to preliminatively observe its antitumor efficacy. The whole study was divided into three stages: dose increment, dose extension and therapeutic effect extension.

Official Title
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A Multicenter, Open Phase I Clinical Study of Safety, Tolerability, Pharmacokinetics, and Efficacy of SHR-1826 for Injection in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: SHR-1826


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide a written informed consent. ≥18 years old ，Male or female. ECOG score is 0 or 1. Subjects with advanced or metastatic solid tumors that have been documented by histopathology and are not responding to or tolerated by standard treatment, or have no effective standard treatment options. Have at least one measurable lesion according to RECIST v1.1 criteria. Expected survival ≥3 months . With good vital organ function. Contraception. Exclusion Criteria: With untreated or active Central nervous system (CNS) tumor metastasis. Subjects with a history or current history of meningeal metastasis. Previous or co-existing malignant tumors. Spinal cord compression that was not treated radically by surgery and/or radiotherapy was excluded. Patients with uncontrolled tumor-related pain. Received systemic antitumor therapy 4 weeks before starting study treatment; Previously receiving small molecule targeted therapy, the interval of not less than 5 half-lives of the drug can be enrolled. Previously received antibody-coupled drug therapy. Have undergone major surgery other than diagnosis or biopsy within 28 days prior to initial dosing; Minor traumatic surgery within 7 days prior to first dosing. First study subjects receiving >30Gy non-radical chest radiation within 28 days prior to administration, >30Gy chest radiation within 24 weeks prior to first administration, and ≤30Gy palliative radiation within 14 days prior to first administration;If previously received radioisotope therapy, the interval of not less than 5 half-lives of the isotope drug can be included. Is participating in another clinical study or the time of first administration is less than 4 weeks from the end of the previous clinical study (last administration), or the 5 half-life of the investigational drug, whichever is the older. The AE caused by previous anti-tumor therapy did not recover to CTCAE v5.0 grade evaluation ≤1. Other severe lung diseases that may interfere with the detection or management of drug-related pulmonary toxicity within the first three months of administration that significantly affect respiratory function; Any autoimmune, connective tissue, or inflammatory disease with lung involvement; Prior left or right total lung resection. Pleural effusion, ascites, or pericardial effusion requiring intervention occurred within 2 weeks prior to the first dose. Have an active autoimmune disease, or other acquired (HIV infection), congenital immunodeficiency disease, or a history of organ transplantation. Have poorly controlled or severe cardiovascular disease. Known hereditary or acquired bleeding and thrombotic tendencies, and clinically significant bleeding symptoms and arterial/venous thrombosis events in the 3 months prior to the first dose. Untreated active hepatitis. Subjects who had a severe infection within 30 days prior to the first dose; Patients with active pulmonary tuberculosis infection within 1 year prior to enrollment were found by medical history or CT examination, or had a history of active pulmonary tuberculosis infection more than 1 year ago but had not received regular treatment. Live attenuated vaccine should be administered within 30 days prior to the first dose. Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study period. Known allergy to any component or excipient of the SHR-1826 product. The presence of other serious physical or mental illnesses or abnormalities in laboratory tests that may increase the risk of participation in the study, or interfere with the study results, as well as conditions that the investigator deems inappropriate to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1826<br>Dose escalation; Dose expansion; Therapeutic effect expansion. | Drug: SHR-1826<br>* dose is calculated based on the subjects' baseline weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity | evaluate the safety in the doses escalation | 21 Days | 
| Maximum tolerated dose or Maximum-administered dose | evaluate the safety in the doses escalation | Approximately 1 year | 
| Recommended Phase 2 dose (RP2D) | evaluate the safety and curative effect in the doses escalation | Approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) of SHR-1826 | To evaluate the pharmacokinetic characteristics of SHR-1826 | Approximately 2 years | 
| Time to maximum concentration (Tmax) of SHR-1826 | To evaluate the pharmacokinetic characteristics of SHR-1826 | Approximately 2 years | 
| Areas under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of SHR-1826 | To evaluate the pharmacokinetic characteristics of SHR-1826 | Approximately 2 years | 
| Areas under the concentration-time curve from time zero extrapolated to infinity (AUCinf) of SHR-1826 | To evaluate the pharmacokinetic characteristics of SHR-1826 | Approximately 2 years | 
| Half-life (t1/2) of SHR-1826 | To evaluate the pharmacokinetic characteristics of SHR-1826 | Approximately 2 years | 
| Mean retention times (MRT) of SHR-1826 | To evaluate the pharmacokinetic characteristics of SHR-1826 | Approximately 2 years | 
| Clearance rate (CL) of SHR-1826 | To evaluate the pharmacokinetic characteristics of SHR-1826 | Approximately 2 years | 
| Volume of distribution at the steady state (Vss) of SHR-1826 | To evaluate the pharmacokinetic characteristics of SHR-1826 | Approximately 2 years | 
| Anti-drug antibody of SHR-1826 | To evaluate the pharmacokinetic characteristics of SHR-1826 | Approximately 2 years | 
| Objective response rate (ORR) | Preliminary evaluation of the effectiveness of SHR-1826 | Approximately 2 years | 
| Duration of response (DoR) | Preliminary evaluation of the effectiveness of SHR-1826 | Approximately 2 years | 
| Disease control rate (DCR) | Preliminary evaluation of the effectiveness of SHR-1826 | Approximately 2 years | 
| Progression free survival (PFS) | Preliminary evaluation of the effectiveness of SHR-1826 | Approximately 2 years | 
| Overall survival (OS) | Preliminary evaluation of the effectiveness of SHR-1826 | Approximately 2 years |