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

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.

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: SHR-1701

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • South Brisbane, New South Wales, Australia, 4101
      • Icon Cancer Care Centre
    • Sydney, New South Wales, Australia
      • Scientia Clinical Research
    • Sydney, New South Wales, Australia
      • Sydney South West Private
  • Western Australia
    • Perth, Western Australia, Australia
      • Linear Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Atridia Pty Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2020
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): February 1, 2023

Study Registration Dates

• First Submitted: November 28, 2019
• First Submitted That Met QC Criteria: March 26, 2020
• First Posted (Actual): March 27, 2020

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 19, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SHR-1701-001AUS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No