NCT03182673

The Study of SHR7390 in Combination With SHR-1210 and SHR3162 in Patients With Advanced Solid Tumors

A Phase I, Open Label, Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SHR7390 Combined With SHR-1210 and SHR3162 in Patients With Advanced Solid Tumors

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: Jiangsu HengRui Medicine Co., Ltd. · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The study consists of the two parts, the first one is SHR7390 combined with SHR-1210, the second one is SHR7390 combined with SHR-1210 and SHR3162. Two parts of the study are separately to assess the safety and tolerability, to define dose limiting toxicity（DLT) and maximum tolerated dose (MTD),to evaluate the pharmacokinetics ,to assess the antitumor activity in patients with advanced solid tumors preliminarily and to recommend reasonable dosage regimen of SHR7390 for the follow-up clinical trial.

Detailed description

This is a phase I, open-label,two parts,dose escalation/expansion clinical study.The safety,tolerance,PK and preliminary efficacy of two-drug combination and three-drug combination were evaluated respectively in the patients with advanced solid tumors that have no any targeted agents as the standard therapies. In the first study part, subjects receiving a single dose of SHR7390 (Run-in) are observed in 7-10 days, then accepted two drug combination therapy, SHR7390 is administered once daily orally for 28 days for a treatment cycle. At the same time, SHR-1210 was given intravenously per 2 weeks at the fixed dose of 200mg. In the second study part, subjects accepted three drug combination therapy, SHR7390 is administered orally for 21 days and discontinued for 7 days in a 28-day treatment cycle,SHR3162 was administered orally twice a day for 28 days at a fixed dose of 100 mg. At the same time, SHR-1210 was given intravenously per 2 weeks at the fixed dose of 200mg. Dose limiting toxicities (DLT) in the first study part will be assessed during the Run-in and first cycle of treatment. the dose escalation is designed by Accelerated Titration Designs during initial accelerated phase. when the significant toxicity or DLT is observed in the Run-in and first cycle of treatment,the accelerated titration trial terminates and subsequent dose escalations are become a conventional design of 3+3 patients. If one adverse event （AE） meets dose limiting toxicity (DLT) criteria at a given dose, 3 additional patients will be enrolled in this dose cohort. If 2 DLTs are determined at a given dose level, the previous dose will be designated as the MTD. Based on preliminary determination of RP2D and sufficient safety data in the first part of the study, the second part of three-drug combination will be carried out. the preset dose of SHR7390 includes RP2D initially determined in the first part of the study and its previous low dose level (for example, RP2D is 0.5 mg/d, while the former low dose is 0.25 mg/d). Dose escalation is a conventional design of 3+3 patients. Additional patients will be enrolled for pharmacokinetic (PK) evaluations at different dose levels based on preliminary safety and tolerability.Each dose level can expand at least 12 subjects , of which 9-12 subjects are PK subjects. Multiple blood samples at designated time points will be collected for PK evaluations (more than 12 subjects are determined by SMC). The safety, tolerability and AEs will be closely monitored throughout the study duration. The preliminary effectiveness and clinical benefits of two-drug combination and three-drug combination will be evaluated.

Conditions

• Solid Tumor

Interventions

Type	Name	Description
DRUG	SHR7390	SHR7390 is provided as white, film-coated,immediate release tablets containing SHR7390 at dosage strengths of 0.125 mg,0.5 mg and 2mg. Multiple tablets of SHR7390 will be administered orally to achieve targeted doses of SHR7390: 0.125 mg-4 mg. Tablets will be administered once daily or for 21 days and discontinued for 7 days with 240 ml water after 2 hours of the meal.
BIOLOGICAL	SHR-1210	SHR-1210 is a humanized anti-PD1 immunoglobulin G4 (IgG4) monoclonal antibody. SHR-1210 is provided as the lyophilized powder,200 mg/vial.SHR-1210 was given with 200mg fixed dose intravenously per 2 weeks at the D1 and D15.Intravenous infusion over 30 min
DRUG	SHR3162	SHR3162 is provided as capsules containing SHR3162 at dosage strengths of 10mg,40mg and 100mg. The capsule of SHR3162 will be orally administered with 240ml water twice a day to achieve targeted doses of SHR3162 and the interval of SHR3162 capsules taken twice a day is about 12 hours.

Timeline

• Start date: 2017-07-24
• Primary completion: 2019-06-12
• Completion: 2019-06-12
• First posted: 2017-06-09
• Last updated: 2022-09-01

Locations

1 site across 1 country: China