Safety, Tolerability and Pharmacokinetics/Pharmacodynamics (PK/PD) of SHR-1603 in Subjects With Advanced Malignancies

Jiangsu HengRui Medicine Co., Ltd.128 enrolled

Overview

SHR-1603-I-101 is an single-arm, open-label, dose finding phase I clinical trial of SHR-1603 in subjects with advanced solid tumor or relapsed/refractory malignant lymphoid diseases. The study drug will be administered by intravenous infusion.

SHR-1603-I-101 is a single-arm, open-label, dose finding, first-in-human(FIH) clinical trial of SHR-1603 intravenous infusion in subjects with advanced solid tumor or relapsed/refractory malignant lymphoid diseases. The primary objective of this study is to evaluate the safety and tolerability of SHR-1603, as well as to determine the maximally tolerated dose(MTD) and define the recommended Phase 2 dose(RP2D) of SHR-1603. The study is consisted of a dose-escalation Part 1 followed by a dose expansion Part 2 and a clinical expansion Part 3. Part 1 will use accelerated titration and 3+3 dose-escalation design to determine MTD. Part 2 will further evaluate the safety, tolerability and PK/PD features of SHR-1603 based on the results of Part 1. Part 3 will include several cohorts of malignancies to collect preliminary efficacy information of SHR-1603.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

128

Conditions

Physiological Effects of Drugs Neoplasms by Histologic Type

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Ages 18 years or older; 2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1; 3. Life expectancy no less than 12 weeks; 4. Pathologically confirmed advanced solid tumor or relapsed/refractory lymphoma with measurable target lesions; 5. Adequate bone marrow, haptic, renal and coagulation function. Exclusion Criteria: 1. Evidence of central nervous system (CNS) involvement; 2. Previously treated with similar agents; 3. History of anticancer treatment within 4 weeks of enrollment (6 weeks for subjects treated with nitrosoureas or mitomycins); 4. Anticipated to be involved in other anti-cancer treatments expect for palliative care during the trial; 5. History of anti-cancer vaccination; or history of vaccination using attenuated vaccines within 4 weeks of enrollment; 6. History of Red blood cell (RBC) transfusion within or treatment with erythropoitin(EPO) within 3 months of enrollment; 7. History of grade 3 or higher thrombolic incidence within 2 years of enrollment, or using antithrombotic/anticoagulant agents; 8. With confirmed immunodeficiency, uncontrolled auto-immune disease, uncontrolled cardiovascular disease, uncontrolled or active infection; 9. Substance abuse.

Outcomes

Primary Outcomes

Adverse events(AE) of SHR-1603

Assessment of the incidence of treatment-emergent AEs

Time frame: 18 months (anticipated)

Dose-limited toxicity (DLT) of SHR-1603

Assessment of the incidence of DLT

Time frame: 18 months(anticipated)

Maximum tolerated dose (MTD) of SHR-1603

The highest dosing level at which no more than 1 of 6 patients has DLT

Time frame: 18 months(anticipated)

Secondary Outcomes

The peak plasma concentration (Cmax) of SHR-1603

The serum concentrations of SHR-1603 at each dose level, between the first and second intravenous administration.

Time frame: 18 months (anticipated)

The area under the plasma concentration versus time curve (AUC) of SHR-1603

The plot of SHR-1603 concentration in blood plasma versus time after intravenous infusion.

Time frame: 18 months (anticipated)

The half-life(t1/2) of SHR-1603

The time required for the serum concentration of SHR-1603 be reduced to half of its peak concentration.

Time frame: 18 months (anticipated)

The objective response rate(ORR) in subjects with advanced tumors treated with SHR-1603

The proportion of patients with reduction in tumor burden. RECIST 1.1(solid tumor) or LUGANO 2014(lymphoma) will be used for assessment.

Time frame: 36 months

The best of response (BOR) in subjects with advanced tumors treated with SHR-1603

The best response recorded from the start of the study treatment until the disease progression. RECIST 1.1(solid tumor) or LUGANO 2014(lymphoma) will be used for assessment.

Time frame: 36 months

The progression free survival (PFS) in subjects with advanced tumors treated with SHR-1603

Time from the first dose of SHR-1603 until disease progression or death. Disease progression will be determined according to RECIST 1.1(solid tumor) or LUGANO 2014(lymphoma).

Time frame: 36 months

The Duration of response (DoR) in subjects with advanced tumors treated with SHR-1603

Time from documentation of tumor response to disease progression. RECIST 1.1(solid tumor) or LUGANO 2014(lymphoma) will be used for assessment.

Time frame: 36 months

The disease control rate (DCR) in subjects with advanced tumors treated with SHR-1603

The percentage of subjects with solid tumor who have achieved complete response(CR), partial response(PR) and stable disease(SD) no less than 24 weeks since start of treatment. RECIST 1.1(solid tumor) or LUGANO 2014(lymphoma) will be used for assessment.

Time frame: 36 months

The clinical benefit rate (CBR) in subjects with advanced tumors treated with SHR-1603

The percentage of subjects with solid tumor who have achieved complete response(CR), partial response(PR) and stable disease(SD). RECIST 1.1(solid tumor) or LUGANO 2014(lymphoma) will be used for assessment.

Time frame: 36 months

SHR-1603 receptor occupation

red blood cell and white blood cell surface receptor occupation will be assessed frequently

Time frame: 30 months

SHR-1603 antibodies

anti SHR-1603 antibodies will be tested frequently

Time frame: 30 months

Safety, Tolerability and Pharmacokinetics/Pharmacodynamics (PK/PD) of SHR-1603 in Subjects With Advanced Malignancies

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes