A Trial of SHR-1701 in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a dose-escalation and dose-expansion Phase 1 trial to evaluate the safety and tolerability of SHR-1701 in subjects with advanced solid tumors.

Detailed Description
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This is a two-part, open-label, multicenter, non-randomized, dose escalation, Phase 1 study of repeated doses of SHR-1701 in subjects with advanced solid tumors who have failed current standard anti-tumor therapies.

Official Title
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A Phase 1, Open-Label, Multi-Center, Non-Randomized, Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of SHR-1701 in Subjects With Advanced Solid Tumors.

Conditions
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Advanced 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: Diagnosed (histologically or cytologically) with solid tumors ECOG Performance Status of 0 or 1 at both the screening and baseline visits Life expectancy ≥12 weeks Adequate laboratory parameters Willing and able to comply with clinic visits and study-related procedures Provide signed informed consent Exclusion Criteria: Known history of hypersensitivity to the study drug Prior malignancy active within the previous 2 years Any investigational or concurrent cancer therapy History of immunodeficiency including seropositivity Systemic antibiotics treatment for ≥ 7 days before the first dose A known history of allogeneic organ transplantation

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose escalation is designed according to a modified 3+3 scheme, in which 3 to 6 subjects will be enrolled in each dose group. Four dose levels of SHR-1701 are planned. After completion of dose escalation, selected cohort(s) will be expanded.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose level 1<br>Subjects will receive a single dose of SHR-1701 at Dose level 1 on Day 1 of each cycle | Drug: SHR-1701<br>* Anti-PD-L1/TGFβ fusion protein<br>|
| Experimental: Dose level 2<br>Subjects will receive a single dose of SHR-1701 at Dose level 2 on Day 1 of each cycle | Drug: SHR-1701<br>* Anti-PD-L1/TGFβ fusion protein<br>|
| Experimental: Dose level 3<br>Subjects will receive a single dose of SHR-1701 at Dose level 3 on Day 1 of each cycle | Drug: SHR-1701<br>* Anti-PD-L1/TGFβ fusion protein<br>|
| Experimental: Dose level 4<br>Subjects will receive a single dose of SHR-1701 at Dose level 2 1 on Day 1 and Day 15 of each cycle | Drug: SHR-1701<br>* Anti-PD-L1/TGFβ fusion protein<br>|
| Experimental: Dose level 5<br>Subjects will receive a single dose of SHR-1701 at Dose level 3 on Day 1 and Day 15 of each cycle | Drug: SHR-1701<br>* Anti-PD-L1/TGFβ fusion protein<br>|
| Experimental: Dose expansion 1<br>Subjects will receive a single dose of SHR-1701 on a selected dose level Day 1 of each cycle | Drug: SHR-1701<br>* Anti-PD-L1/TGFβ fusion protein<br>|
| Experimental: Dose expansion 2<br>Subjects will receive a single dose of SHR-1701 on a selected dose level on Day 1 of each cycle | Drug: SHR-1701<br>* Anti-PD-L1/TGFβ fusion protein<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Number of subjects with adverse events (AEs) | Screening up to study completion, an average of 1 year | 
| Laboratory results | Number of subjects with laboratory tests findings of potential clinical importance | Screening up to study completion, an average of 1 year | 
| Vital signs | Incidence of vital sign abnormalities | Screening up to study completion, an average of 1 year | 
| Electrocardiogram | Number of subjects with clinically significant abnormal ECG QT Interval | Screening up to study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic - Cmax | Maximum observed plasma concentration (Cmax) of SHR-1701 | Pre-dose, 10min(±2min), 1h(±5min), 2h(±5min), 6h(±10min) Post-dose on Cycle1 Day 1, pre-dose on Day 2, 3, 4, 8, 15 | 
| Pharmacokinetic - AUC∞ | Area under the concentration-time curve from time 0 to infinity of SHR-1701 | Pre-dose, 10min(±2min), 1h(±5min), 2h(±5min), 6h(±10min) Post-dose on Cycle1 Day 1, pre-dose on Day 2, 3, 4, 8, 15 | 
| Pharmacokinetic - Tmax | Time to Cmax of SHR-1701 | Pre-dose, 10min(±2min), 1h(±5min), 2h(±5min), 6h(±10min) Post-dose on Cycle1 Day 1, pre-dose on Day 2, 3, 4, 8, 15 | 
| Pharmacokinetic - CL/F | Apparent clearance of SHR-1701 | Pre-dose, 10min(±2min), 1h(±5min), 2h(±5min), 6h(±10min) Post-dose on Cycle1 Day 1, pre-dose on Day 2, 3, 4, 8, 15 | 
| Pharmacokinetic - Vz/F | Apparent volume of distribution during terminal phase of SHR-1701 | Pre-dose, 10min(±2min), 1h(±5min), 2h(±5min), 6h(±10min) Post-dose on Cycle1 Day 1, pre-dose on Day 2, 3, 4, 8, 15 | 
| Pharmacokinetic - t1/2 | Terminal elimination half-life | Pre-dose, 10min(±2min), 1h(±5min), 2h(±5min), 6h(±10min) Post-dose on Cycle1 Day 1, pre-dose on Day 2, 3, 4, 8, 15 | 
| Pharmacodynamics- ADA | Anti-drug antibody of PD-L1 | Pre-dose on Day1 of cycle 2,3,4,5,7,9,13,17 |