SHR-1701 in Subjects With Metastatic or Locally Advanced Solid Tumors

Study Overview
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Brief Summary
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The main purpose of this study is to assess the safety and tolerability of SHR-1701 at different dose levels. Study consists of dose-escalation part and an expansion part in subjects with metastatic or locally advanced solid tumors.

Detailed Description
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This is a Phase I, open-label, multiple-ascending dose trial. Study consists of dose-escalation part in subjects with metastatic or locally advanced solid tumors, and expansion part with selected indications.

Official Title
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A Phase I, Open-label Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of SHR-1701 in Subjects With Metastatic or Locally Advanced Solid Tumors With Expansion to Selected Indications

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: SHR-1701


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide signed informed consent form, and able to comply with all procedures. Histologically or cytologically proven metastatic or locally advanced solid tumors. Male or female subjects aged 18-75 years. Life expectancy >= 12 weeks as judged by the Investigator. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry. Disease must be measurable with at least 1 uni dimensional measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Adequate hematological, hepatic and renal function as defined in the protocol Other protocol-defined inclusion criteria could apply. Exclusion Criteria: Prior therapy with an anti-PD1, anti-PD-L1, anti-CTLA-4 or a TGFb inhibitor. Anticancer treatment within 28 days before the first dose of study drug. Major surgery within 28 days before start of trial treatment. Systemic therapy with immunosuppressive agents within 7 days prior to the first dose of study drug; or use any investigational drug within 28 days before the start of trial treatment. With any active autoimmune disease or history of autoimmune disease. With active central nervous system (CNS) metastases causing clinical symptoms or requiring therapeutic intervention. Clinically significant cardiovascular and cerebrovascular diseases History of immunodeficiency including seropositive for human immunodeficiency virus (HIV), or other acquired or congenital immunedeficient disease, or any active systemic viral infection requiring therapy. Previous malignant disease (other than the target malignancy to be investigated in the trial) within the last 2 years. Subjects with history of cervical carcinoma in situ, superficial or non-invasive bladder cancer or basal cell or squamous cell cancer in situ previously treated with curative intent are NOT excluded. Receipt of any organ transplantation, including allogeneic stem-cell transplantation Other protocol-defined exclusion criteria could apply

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1701<br>intravenous infusion | Drug: SHR-1701<br>* Subjects will receive an intravenous infusion of SHR-1701 in a pre-set dose escalation until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose escalation part： Safety and tolerability of SHR-1701 in advanced malignancies. | Number of Subjects who occurs dose-limiting toxicity (DLTs). | Up to 3/4 weeks. | 
| Clinical expansion Part: Objective Response Rate（ORR） | ORR is define as the percentage of participants in the analysis population who havea Complete Response(CR:Disappearance of all target lesions)or a Partial Response(PR :30% decrease in the sum of diameter of target lesions) per RECIST 1.1. | Up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical expansion Part: Safety of SHR-1701 | Number of subjects who occurs treatment-related Adverse Events(AEs） | Up to 4 weeks after last treatment | 
| Clinical expansion Part: Disease Control Rate(DCR) per RECIST1.1 | DCR is define as the percentage of participants in the analysis population who have a CR,PR or SD per RECIST 1.1. | Up to 6 weeks | 
| Clinical expansion Part: Duration of Response （DOR）per RECIST1.1 | DOR is define as the time from first documented evidence of CR or PR until disease progression per RECIST 1.1 | Up to 6 weeks | 
| Clinical expansion Part:Progression-free survival(PFS) per RECIST1.1 | PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 | 12months (anticipated) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SHR-1701, Solid tumor, Metastatic or locally advanced solid tumors