A Study of SHR-1802 in Patients With Advanced Solid Tumor

Study Overview
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Brief Summary
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To assess the safety and tolerability of SHR-1802 combined with camrelizumab and famitinib in subjects with advanced solid tumor and to determine the dose-limiting toxicity (DLT)，recommended phase II dose (RP2D) and assess objective response rate (ORR) assessed by the investigator based on RECIST v1.1 criteria.

Official Title
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A Phase Ⅰb/Ⅱ Dose-exploration and Efficacy-expansion Study of SHR-1802 Combined With Camrelizumab for Injection and Famitinib Malate Capsules for the Treatment of Advanced Solid Tumor

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: SHR-1802＋camrelizumab + famitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study; Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; Has a life expectancy≥ 3 months; At least one measurable lesion according to RECIST v1.1; Pathologically confirmed advanced solid tumor; Adequate bone marrow reserve and organ function. Exclusion Criteria: Have received prior therapy with camrelizumab, and famitinib; Received anti-tumor therapies such as chemotherapy, radiotherapy, biological therapy, targeted therapy, or immunotherapy within 4 weeks before the first dose of the treatment; Underwent a major surgery other than diagnosis or biopsy within 4 weeks before the first dose of the treatment; Have uncontrolled clinically symptomatic pleural effusion, pericardial effusion, or ascites; Have known history of arterial/venous thrombosis within 6 months prior to the first dose of the treatment, such as cerebrovascular accidents, deep vein thrombosis and pulmonary embolism; Grade II-IV cardiac insufficiency as per the New York Heart Association (NYHA) criteria; arrhythmia requiring long-term drug control; unstable angina or acute myocardial infarction within 6 months before the first dose of the treatment; Have other potential factors that may affect the study results or result in the premature discontinuation as determined by the investigator, such as alcoholism, drug abuse, substance abuse, other serious diseases (including mental illness) requiring concomitant treatment, serious laboratory abnormalities, or family or social factors that could affect the safety of medication.

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
Intervention Model: Single Group Assignment
Interventional Model Description: Dose-escalation: Traditional 3+3 dose-escalation design. Dose-expansion: 10 to 12 subjects (included subjects of the dose-escalation part) will be enrolled in each tolerable dose level. Efficacy-expansion: After determination of the recommended dose for Phase II (RP2D), selected cohorts with different tumor types will be expanded.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1802 for injection combined with Camrelizumab for Injection and Famitinib Malate Capsules<br> | Drug: SHR-1802＋camrelizumab + famitinib<br>* SHR-1802 for injection，q3w； Camrelizumab for injection, q3w; Famitinib malate capsules, qd.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) |  | 4 weeks | 
| Recommended phase II dose (RP2D) |  | up to 1 years | 
| ORR | Objective Response Rate, determined according to RECIST v1.1 criteria | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DOR | Duration of Response, determined according to RECIST v1.1 criteria | up to 2 years | 
| DCR | Disease Control Rate, determined according to RECIST v1.1 criteria | up to 2 years | 
| PFS assessed by investigator | Progression Free Survival, determined according to RECIST v1.1 criteria | up to 2 years | 
| TTR | Time to Response，determined according to RECIST v1.1 criteria | up to 2 years | 
| OS (overall survival) | From date of treatment start to any cause death or last follow-up | up to 2 years | 
| 12-month OS rate |  | from the date of the first dose up to 2 years | 
| AEs+SAEs | Adverse Events and Serious Adverse Events assessed by CTCAE v5.0 | from the first drug administration to within 90 days for the last drug dose | 
| Concentration of drug in serum | Serum concentration of Camrelizumab for Injection and SHR-1802 for injection. | 0.5 hour before the first dose up to 30 days after last dose | 
| Concentration of drug in plasma | Plasma concentration of Famitinib malate capsule and its metabolite. | n the second cycle，predose 1 hour and 6 hours post-dose；In cycle 3, cycle 4, cycle 6, cycle 8, and cycle 10，predose 1 hour（each cycle is 21 days） | 
| Count of T lymphocyte subsets | Count of CD4+ T lymphocyte subsets in peripheral blood；Count of CD8+ T lymphocyte subsets in peripheral blood. | 30 minutes before the first dose of SHR-1802, the 4th and 8th days after the first injection | 
| Percentage of T lymphocyte subsets | Percentage of CD4+ T lymphocyte subsets in peripheral blood；Percentage of CD8+ T lymphocyte subsets in peripheral blood. | 30 minutes before the first dose of SHR-1802, the 4th and 8th days after the first injection | 
| ADA | Anti-drug antibody of Camrelizumab for Injection and SHR-1802 for injection | up to 30 days after last dose | 
| Nab | Neutralizing Antibody of Camrelizumab for Injection and SHR-1802 for injection. | up to 30 days after last dose |