A Single-arm, Multi-center, Phase Ⅱ Clinical Study to Evaluate the HLX10 Monotherapy for the Treatment of Unresectable or Metastatic Microsatellite Instability-high (MSI-H) or Mismatch Repair Deficient (dMMR) Solid Tumors That Failed to Respond to Standard Therapy

Shanghai Henlius Biotech33 sites in 1 country108 target enrollmentJuly 15, 2019

ConditionsMSI-H Solid Malignant Tumor

InterventionsHLX10

DrugsHLX10

Overview

Phase: Phase 2
Intervention: HLX10
Conditions: MSI-H Solid Malignant Tumor
Sponsor: Shanghai Henlius Biotech
Enrollment: 108
Locations: 33
Primary Endpoint: ORR
Status: Recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

It is a single-arm, open-label, multicenter, phase II clinical study to evaluate the clinical efficacy and safety of HLX10 monotherapy for the treatment of patients with unresectable or metastatic MSI-H or dMMR solid tumors who have progressed or intolerable after standard therapy.This study consists of three periods, screening period (28 days), treatment period and follow-up period (including safety follow-up, survival follow-up).Subjects can be enrolled into this study only if they meet inclusion criteria and do not meet exclusion criteria. The enrolled subjects will receive an intravenous infusion of HLX10 (3 mg/kg) once every 2 weeks until the loss of clinical benefit, death, intolerable toxicity, withdrawal of informed consent or other reasons as specified in the protocol, or up to the longest treatment duration-2 years (52 dosing periods) (whichever occurs earlier).

Registry

clinicaltrials.gov

Start Date

July 15, 2019

End Date

June 30, 2026

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Henlius Biotech

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects who meet all of the following criteria are allowed to be enrolled into this study:
•Volunteer to participate in this clinical study; completely understand and know this study as well as sign the informed consent form (ICF); be willing to follow and be able to complete all study procedures;
•Age ≥ 18 years and ≤ 75 years when ICF is signed;
•Patients with unresectable or metastatic MSI-H or dMMR malignant solid tumors which are histopathologically or/and cytologically confirmed by the central laboratory or study sites;
•Patients who have disease progression or intolerable reactions after the currently available standard anti-cancer treatment previously received;
•The interval between the end of previous systemic anti-tumor treatment and the first dosing of if this study must be ≥ 2 weeks. In addition, treatment-related AEs recover to NCI-CTCAE v4.03 ≤ grade 1 (excluding grade 2 alopecia).
•There is at least one measurable lesion assessed by IRRC according to the requirements of RECIST version 1.1 (Appendix 1).
•Note: measurable lesions cannot be selected from the previous radiotherapy sites. If the target lesion of the previous radiotherapy sites is the only one available lesion, the investigator is required to provide imaging data before and after significant progression of such lesion.
•Subjects must provide tumor tissues and blood samples for the determination of MSI, tumor mutational burden (TMB), PD-L1 expression level (if the test results of the above parameters by the central laboratory specified by this study are available, the subjects are allowed not to receive repeated tests).
•Note: it is recommended to provide formalin fixed tumor tissue samples collected from non-radiotherapy sites within 6 months prior to the first dosing of investigational product, paraffin embedded tumor samples (preferred), or formalin fixed paraffin embedded tumor samples or unstained newly sliced serial sections (glass slides). Moreover, the corresponding pathological reports of the above samples must also be provided. Freshly collected samples, excision, core needle biopsy, resection, incision, punching or forceps biopsies are within the acceptable range (newly-obtained tissues preferred). The aspiration samples (i.e., lack of complete tissue structure and only cell suspension and/or cell smears are provided), brushing samples, cell precipitation samples from pleural or peritoneal effusion are not acceptable. The requirements for tissue samples are provided in laboratory operating manual in detail.

Exclusion Criteria

•Subjects who meet any of the following criteria are not allowed to be enrolled in this study:
•Subjects who plan to undergo or previously underwent organ or bone marrow transplantation.
•Uncontrollable pleural effusion, pericardial effusion or ascites after appropriate intervention measures.
•Subjects with known or screening test-confirmed active central nervous system (CNS) metastasis and/or carcinomatous meningitis; However, the following subjects are allowed to be enrolled:
•subjects with asymptomatic brain metastasis (i.e. without progressive central nervous system symptoms caused by brain metastatic lesions, without the requirement of corticosteroids treatment, and lesion size ≤1.5cm) are allowed to participate in this study, however, it is necessary to perform regular brain imaging tests for disease sites.
•subjects with brain metastasis after treatment, and brain metastatic lesions are stable for at least 1 month, without evidence of new or expanded brain metastasis, and steroids are discontinued 3 days prior to the first dose of the investigational product. Stable brain metastasis in this definition should be confirmed before the first dose of the investigational product.
•Subjects with spinal cord compression which cannot be radically treated through surgery and/or radiotherapy, or subjects previously diagnosed with spinal cord compression with no post-treatment clinical evidence showing stable disease ≥ 1 week before the first dose of the investigational product.
•Imaging test results show definit tumor invasion of thoracic great vessels.
•Occurrence of myocardial ischemia above grade Ⅱ , or myocardial infarction, unstable angina pectoris, inadequately controlled arrhythmia (including QTc interval ≥ 450 ms for males, and ≥ 470 ms for females) within half a year before the first dose of the investigational product (QTc interval is calculated based on Fridericia formula).
•Grade Ⅲ or Ⅳ cardiac dysfunction based on New York Heart Association (NYHA) Functional Classification (appendix Ⅲ) or echocardiography test showing left ventricular ejection fraction (LVEF) \< 50%.

Arms & Interventions

HLX10

Intervention: HLX10

Outcomes

Primary Outcomes

ORR

Time Frame: up to 2 years

Objective response rate(assessed by independent radiological review committee (IRRC) based on the RECIST Version 1.1)

Secondary Outcomes

6-month OS rate(from the date of first dose unitl the date of 6-month)
ORR(up to 2 years)
PFS(from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years)
OS(from the date of first dose unitl the date of death from any cause，assessed up to 2 years)
6-month PFS rate(the proportion of subjects who have time interval over 6 months between the first dose and disease progression or death)
DOR DOR(from the date when CR or PR (whichever recorded earlier) is firstly achieved until the date when disease progression or death is firstly recorded (whichever occurs earlier),assessed up to 2 years)