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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/27/2021.

A Clinical Study to Evaluate HLX10 Monotherapy for the Treatment of MSI-H or dMMR Solid Tumors That Failed to Respond to Standard Therapy

Clinicaltrials.gov identifier NCT03941574

Recruitment Status Recruiting

First Posted May 8, 2019

Last update posted July 30, 2019

Study Description

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).

  • Condition or Disease:MSI-H Solid Malignant Tumor
  • Intervention/Treatment: Drug: HLX10
  • Phase: Phase 2
Detailed Description

N/A

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 60 participants
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: 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
  • Actual Study Start Date: July 2019
  • Estimated Primary Completion Date: December 2020
  • Estimated Study Completion Date: April 2021
Arms and interventions
Arm Intervention/treatment
Experimental: HLX10
Drug: HLX10
HLX10 developed by our company is sterile intravenous injection, with specification of 100 mg/10 mL/bottle. The main ingredient is 10.0 mg/mL of recombinant humanized anti-PD-1 monoclonal antibody. The excipients include 0.95 mg/mL citric acid (citric acid monohydrate), 4.56 mg/mL sodium citrate (sodium citrate dihydrate), 3.0 mg/mL sodium chloride, 30.0 mg/mL mannitol and 0.20 mg/mL polysorbate 80 (tween 80), with pH of 5.5.
Outcome Measures
  • Primary Outcome Measures: 1. 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 Outcome Measures: 1. ORR [ Time Frame: up to 2 years ]
    Objective response rate (assessed by the investigators based on the RECIST Version 1.1)
  • 2. ORR [ Time Frame: up to 2 years ]
    Objective response rate (assessed by independent radiological review committee (IRRC) based on the iRECIST)
  • 3. 6-month OS rate [ Time Frame: from the date of first dose unitl the date of 6-month ]
    6-month overall survival rate
  • 4. OS [ Time Frame: from the date of first dose unitl the date of death from any cause,assessed up to 2 years ]
    Overall survival (OS)
  • 5. 6-month PFS rate [ Time Frame: the proportion of subjects who have time interval over 6 months between the first dose and disease progression or death ]
    6-month progression-free survival (PFS) rate
  • 6. PFS [ Time Frame: from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years ]
    Progression-free survival (assessed by independent radiological review committee (IRRC) based on RECIST v1.1, iRECIST)
  • 7. PFS [ Time Frame: from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years ]
    Progression-free survival (assessed by the investigators based on RECIST v1.1)
  • 8. DOR DOR [ Time Frame: 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 ]
    Duration of response
Eligibility Criteria
  • Ages Eligible for Study: 18 to 75 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
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.

- ECOG performance status score (Appendix II) of 0 or 1 within 7 days before the first
dose of invetigational product;

- Life expectancy ≥12 weeks;

- Negative HBsAg; patients with positive HBsAg or HBcAb test results can be enrolled
only if Hepatitis B virus (HBV) DNA test results are negative.

11.Negative HCV antibody; patients with positive HCV antibody or HCV-RNA test results
can be enrolled only if ALT and AST are CTCAE v4.03 ≤ grade 1 (i.e., ≤ 3×ULN);
subjects concurrently infected with hepatitis B and hepatitis C are excluded.

- Normal function of main organs, and the following criteria are met (within the 14 days
before the first injection of investigational product, patients have not received the
treatment with blood transfusion, albumin, recombinant human thrombopoietin or colony
stimulating factor (CSF)):

- Female subjects must meet the following criteria:

① Menopause (defined as no menstruation for at least one year, and no other confirmed
reasons other than menopause), or② Received surgical sterilization (ovariectomy and/or
hysterectomy), or③ Subjects who are able to bear or father a child must meet the
following criteria:

- Serum pregnancy test must be negative within 7 days before the first dosing, and

- Agree to use contraceptive methods with an annual failure rate of < 1% or maintain sexual abstinence (avoid heterosexual intercourse) (from the signing of informed consent form to at least 120 days after the last dose of investigational product) (contraceptive methods with an annual failure rate of < 1% include bilateral tubal ligation, male sterilization, correct use of hormonal contraceptives which may inhibit ovulation, hormone-releasing intrauterine device and copper intrauterine device), and - Breast-feeding is not allowed. - Male subjects should meet the criteria below: agree to maintain sexual abstinence (avoid heterosexual intercourse) or use contraceptive methods, with requirements detailed below: if the partners of male subjects have childbearing potential or become pregnant, male subjects must maintain sexual abstinence or use condoms to prevent drug exposure to embryos during administration period of investigational product and within at least 120 days after after the last dose of investigational product. The reliability of sexual abstinence should be evaluated based on the duration of clinical studies, preference of the subjects and daily life style. Regular sexual abstinence (e.g., calendar days, ovulation period, basal body temperature or post-ovulation period contraceptive methods) and coitus interruptus are disqualified contraceptive methods. 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: 1. 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. 2. 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) 10 mg/day
prednisone or equivalent dose of similar drugs) or other immunosuppressive
therapies within 14 days before the first administration of investigational
product or during the study period; However, the following conditions are allowed
to be enrolled: in the event of no active autoimmune diseases, inhalation or
topical use of steroids or adrenaline alternative treatment of effective dose of
prednisone ≤ 10 mg/day are allowed.

- Presence of any active infection requiring systemic anti-infection treatment
within 14 days before the first administration of investigational product.

- Subjects who have received major surgery within 28 days before the first
administration of investigational product, by "major surgery", it meant that the
patient needs at least three weeks to recover following the surgery before being
able to receive the study treatment. Enrollment through tumor puncture or lymph
node biopsy is allowed.

- Received radical radiotherapy within 3 months before the first administration of
investigational product.

Note: palliative radiotherapies for bones or superficial lesions are acceptable. The course
of treatment should be in accordance with the local standard and has ended 14 days before
the first administration. Radiotherapy covering more than 30% of the bone marrow area is
not allowed within 28 days prior to the first dose.

- Other anti-tumor treatments such as chemotherapy, targeted therapy or radiotherapy
(excluding palliative radiotherapy) may be received during the study period.

- Previously received treatment with any T cells costimulation or immune checkpoint,
including but not limited to cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)
inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors or other targeted T cells drugs.

- Subjects are participating in other clinical studies, or the time interval between the
initiation of treatment planned in this study and end of investigational product
treatment in the previous clinical study is less than 14 days.

- Known serious hypersensitivity history to any monoclonal antibody or the excipients of
investigational product.

- Pregnant or lactating women.

- Known history of abuse of psychotropic drugs or drug addiction; Subjects who have
stopped drinking are allowed to be enrolled.

- The subjects have other factors which may cause premature termination of this study at
the discretion of the investigators.

Contacts and Locations
Contacts

Contact: ShuKui Qin 86-025-80864362 luolinhua0513@163.com

Locations

China, Jiangsu
Nanjing Bayi Hospital Ethics Committee
Nanjing

Sponsors and Collaborators

Shanghai Henlius Biotech

More Information
  • Responsible Party: Shanghai Henlius Biotech
  • ClinicalTrials.gov Identifier: NCT03941574 History of Changes
  • Other Study ID Numbers: HLX10-010-MSI201
  • First Posted: May 8, 2019 Key Record Dates
  • Last Update Posted: July 30, 2019
  • Last Verified: July 2019
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: Neoplasms