search
Back to results

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

Primary Purpose

Physiological Effects of Drugs, Neoplasms by Histologic Type, Lymphoma

Status
Suspended
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
SHR-1603
Sponsored by
Jiangsu HengRui Medicine Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Physiological Effects of Drugs focused on measuring advanced solid tumor, R/R lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Shanghai East Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SHR-1603

Arm Description

Multiple escalating doses of SHR-1603

Outcomes

Primary Outcome Measures

Adverse events(AE) of SHR-1603
Assessment of the incidence of treatment-emergent AEs
Dose-limited toxicity (DLT) of SHR-1603
Assessment of the incidence of DLT
Maximum tolerated dose (MTD) of SHR-1603
The highest dosing level at which no more than 1 of 6 patients has DLT

Secondary Outcome Measures

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.
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.
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.
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.
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.
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).
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.
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.
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.
SHR-1603 receptor occupation
red blood cell and white blood cell surface receptor occupation will be assessed frequently
SHR-1603 antibodies
anti SHR-1603 antibodies will be tested frequently

Full Information

First Posted
October 25, 2018
Last Updated
March 18, 2021
Sponsor
Jiangsu HengRui Medicine Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT03722186
Brief Title
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

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Suspended
Why Stopped
Business Decision
Study Start Date
November 13, 2018 (Actual)
Primary Completion Date
April 4, 2019 (Actual)
Study Completion Date
October 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu HengRui Medicine Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Physiological Effects of Drugs, Neoplasms by Histologic Type, Lymphoma, Hematologic Neoplasms, Immunotherapy, Advanced Cancer
Keywords
advanced solid tumor, R/R lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
128 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SHR-1603
Arm Type
Experimental
Arm Description
Multiple escalating doses of SHR-1603
Intervention Type
Drug
Intervention Name(s)
SHR-1603
Intervention Description
SHR-1603 monotherapy
Primary Outcome Measure Information:
Title
Adverse events(AE) of SHR-1603
Description
Assessment of the incidence of treatment-emergent AEs
Time Frame
18 months (anticipated)
Title
Dose-limited toxicity (DLT) of SHR-1603
Description
Assessment of the incidence of DLT
Time Frame
18 months(anticipated)
Title
Maximum tolerated dose (MTD) of SHR-1603
Description
The highest dosing level at which no more than 1 of 6 patients has DLT
Time Frame
18 months(anticipated)
Secondary Outcome Measure Information:
Title
The peak plasma concentration (Cmax) of SHR-1603
Description
The serum concentrations of SHR-1603 at each dose level, between the first and second intravenous administration.
Time Frame
18 months (anticipated)
Title
The area under the plasma concentration versus time curve (AUC) of SHR-1603
Description
The plot of SHR-1603 concentration in blood plasma versus time after intravenous infusion.
Time Frame
18 months (anticipated)
Title
The half-life(t1/2) of SHR-1603
Description
The time required for the serum concentration of SHR-1603 be reduced to half of its peak concentration.
Time Frame
18 months (anticipated)
Title
The objective response rate(ORR) in subjects with advanced tumors treated with SHR-1603
Description
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
Title
The best of response (BOR) in subjects with advanced tumors treated with SHR-1603
Description
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
Title
The progression free survival (PFS) in subjects with advanced tumors treated with SHR-1603
Description
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
Title
The Duration of response (DoR) in subjects with advanced tumors treated with SHR-1603
Description
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
Title
The disease control rate (DCR) in subjects with advanced tumors treated with SHR-1603
Description
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
Title
The clinical benefit rate (CBR) in subjects with advanced tumors treated with SHR-1603
Description
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
Title
SHR-1603 receptor occupation
Description
red blood cell and white blood cell surface receptor occupation will be assessed frequently
Time Frame
30 months
Title
SHR-1603 antibodies
Description
anti SHR-1603 antibodies will be tested frequently
Time Frame
30 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ages 18 years or older; Eastern Cooperative Oncology Group (ECOG) performance status 0-1; Life expectancy no less than 12 weeks; Pathologically confirmed advanced solid tumor or relapsed/refractory lymphoma with measurable target lesions; Adequate bone marrow, haptic, renal and coagulation function. Exclusion Criteria: Evidence of central nervous system (CNS) involvement; Previously treated with similar agents; History of anticancer treatment within 4 weeks of enrollment (6 weeks for subjects treated with nitrosoureas or mitomycins); Anticipated to be involved in other anti-cancer treatments expect for palliative care during the trial; History of anti-cancer vaccination; or history of vaccination using attenuated vaccines within 4 weeks of enrollment; History of Red blood cell (RBC) transfusion within or treatment with erythropoitin(EPO) within 3 months of enrollment; History of grade 3 or higher thrombolic incidence within 2 years of enrollment, or using antithrombotic/anticoagulant agents; With confirmed immunodeficiency, uncontrolled auto-immune disease, uncontrolled cardiovascular disease, uncontrolled or active infection; Substance abuse.
Facility Information:
Facility Name
Shanghai East Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200120
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs