Advanced Solid Tumor
Conditions
Brief summary
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
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.
Interventions
DRUGSHR-1701
Anti-PD-L1/TGFβ fusion protein
Sponsors
Atridia Pty Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Screening up to study completion, an average of 1 year | Number of subjects with adverse events (AEs) |
| Laboratory results | Screening up to study completion, an average of 1 year | Number of subjects with laboratory tests findings of potential clinical importance |
| Vital signs | Screening up to study completion, an average of 1 year | Incidence of vital sign abnormalities |
| Electrocardiogram | Screening up to study completion, an average of 1 year | Number of subjects with clinically significant abnormal ECG QT Interval |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic - Vz/F | 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 | Apparent volume of distribution during terminal phase of SHR-1701 |
| Pharmacokinetic - Cmax | 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 | Maximum observed plasma concentration (Cmax) of SHR-1701 |
| Pharmacodynamics- ADA | Pre-dose on Day1 of cycle 2,3,4,5,7,9,13,17 | Anti-drug antibody of PD-L1 |
| Pharmacokinetic - t1/2 | 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 | Terminal elimination half-life |
| Pharmacokinetic - AUC∞ | 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 | Area under the concentration-time curve from time 0 to infinity of SHR-1701 |
| Pharmacokinetic - Tmax | 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 | Time to Cmax of SHR-1701 |
| Pharmacokinetic - CL/F | 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 | Apparent clearance of SHR-1701 |
Countries
Australia
Outcome results
None listed