The main purpose of this Phase I study is to access the safety and tolerability of SHR-1701 at different dose levels. It is hoped to find out the recommended dose for Phase II/III.
This is a Phase I, open-label trial in patients with metastatic or locally advanced solid tumor. There are three parts of the study: a dose-escalation part, a dose-expansion part, and a clinical expansion part. Dose escalation part is a standard "3+3" cohort design, for which 3 or 6 subjects will be enrolled at each dose level depending on the occurrence of dose-limiting toxicities (DLTs). Dose-expansion means that at least 10 subjects (included subjects of the dose-escalation part) will be selected in 2 - 3 dose levels to focus on the pharmacokinetics (PK) / pharmacodynamic (PD) features. After determination of the recommended dose for Phase II (RP2D), clinical expansion will be opened. Many more subjects will be invited to take part in the study and received the study drug at the RP2D. Additional purpose of the study is to find out whether the study drug has anti-tumor effects.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
206
Subjects will receive an intravenous infusion of SHR-1701 in a dose escalation until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGSafety and tolerability profile of SHR-1701
Number of Subjects who occurs dose-limiting toxicity (DLTs)
Time frame: Up to week 3
Objective Response Rate (ORR) assessed by site investigator as per RECIST 1.1
Time frame: Screening up to study completion, an average of 1 year
Area under the plasma concentration versus time curve (AUC) of SHR-1701
Time frame: Up to 4 weeks after last treatment
Peak Plasma Concentration (Cmax) of SHR-1701
Time frame: Up to 4 weeks after last treatment
Half-time (t1/2) of SHR-1701
Time frame: Up to 4 weeks after last treatment
Pharmacodynamic features of SHR-1701
SHR-1701 receptor occupation
Time frame: 12 months (anticipated)
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors
ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ¡Ý30% decrease in the sum of diameters of target lesions) per RECIST 1.1.
Time frame: 12 months (anticipated)
Disease Control Rate (DCR) per RECIST 1.1
DCR is defined as the percentage of participants in the analysis population who have a CR, PR or SD per RECIST 1.1.
Time frame: 12 months (anticipated)
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Best Overall Response (BOR) per RECIST 1.1
Time frame: 12 months (anticipated)
Immunogenicity of SHR-1701
anti SHR-1603 antibodies (ADA)
Time frame: 12 months (anticipated)
Trough plasma concentration (C trough) of SHR-1701
Time frame: Up to 4 weeks after last treatment
Immunogenicity of SHR-1701
Time frame: 12 months (anticipated)
Disease Control Rate (DCR) per RECIST 1.1
Time frame: 12 months (anticipated)
Clinical Benefit Rate(CBR) per RECIST 1.1
Time frame: 12 months (anticipated)
Progression-Free Survival (PFS) per RECIST 1.1
Time frame: 12 months (anticipated)
Duration of Response (DoR) per RECIST 1.1
Time frame: 12 months (anticipated)
Overall Survival (OS)
Time frame: 12 months (anticipated)