Clinical trial NCT03722186: Safety, Tolerability and Pharmacokinetics/Pharmacodynamics (PK/PD) of SHR-1603 in Subjects With Advanced Malignancies
Official title: An Open-label, Single-arm, Phase I Study of the Safety, Tolerability and Pharmacokinetic/Pharmacodynamic Characteristics of SHR-1603 in Subjects With Advanced Solid Tumor or Relapsed/Refractory Lymphoma
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
Conditions: Physiological Effects of Drugs
Neoplasms by Histologic Type
Lymphoma
Hematologic Neoplasms
Immunotherapy
Advanced Cancer
Keywords: advanced solid tumor
R/R lymphoma
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-10-26
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events(AE) of SHR-1603
timeFrame: 18 months (anticipated)
measure: Dose-limited toxicity (DLT) of SHR-1603
timeFrame: 18 months(anticipated)
measure: Maximum tolerated dose (MTD) of SHR-1603
timeFrame: 18 months(anticipated)
Secondary outcomes:
measure: The peak plasma concentration (Cmax) of SHR-1603
timeFrame: 18 months (anticipated)
measure: The area under the plasma concentration versus time curve (AUC) of SHR-1603
timeFrame: 18 months (anticipated)
measure: The half-life(t1/2) of SHR-1603
timeFrame: 18 months (anticipated)
measure: The objective response rate(ORR) in subjects with advanced tumors treated with SHR-1603
timeFrame: 36 months
measure: The best of response (BOR) in subjects with advanced tumors treated with SHR-1603
timeFrame: 36 months
measure: The progression free survival (PFS) in subjects with advanced tumors treated with SHR-1603
timeFrame: 36 months
measure: The Duration of response (DoR) in subjects with advanced tumors treated with SHR-1603
timeFrame: 36 months
measure: The disease control rate (DCR) in subjects with advanced tumors treated with SHR-1603
timeFrame: 36 months
measure: The clinical benefit rate (CBR) in subjects with advanced tumors treated with SHR-1603
timeFrame: 36 months
measure: SHR-1603 receptor occupation
timeFrame: 30 months
measure: SHR-1603 antibodies
timeFrame: 30 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
Study officials:
References: