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

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

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.

Study Overview

• Status: Suspended
• Conditions: Neoplasms by Histologic Type; Lymphoma; Hematologic Neoplasms; Advanced Cancer; Immunotherapy; Physiological Effects of Drugs
• Intervention / Treatment: Drug: SHR-1603

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.

• Study Type: Interventional
• Enrollment (Anticipated): 128
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200120
      • Shanghai East Hospital

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:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SHR-1603; Multiple escalating doses of SHR-1603	Drug: SHR-1603; SHR-1603 monotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events(AE) of SHR-1603	Assessment of the incidence of treatment-emergent AEs	18 months (anticipated)
Dose-limited toxicity (DLT) of SHR-1603	Assessment of the incidence of DLT	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	18 months(anticipated)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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).	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.	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.	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.	36 months
SHR-1603 receptor occupation	red blood cell and white blood cell surface receptor occupation will be assessed frequently	30 months
SHR-1603 antibodies	anti SHR-1603 antibodies will be tested frequently	30 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 13, 2018
• Primary Completion (ACTUAL): April 4, 2019
• Study Completion (ANTICIPATED): October 1, 2021

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (ACTUAL): October 26, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2021
• Last Update Submitted That Met QC Criteria: March 18, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: advanced solid tumor; R/R lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Neoplasms; Lymphoma; Hematologic Neoplasms; Neoplasms by Histologic Type
• Other Study ID Numbers: SHR-1603-I-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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