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

NCT03941574 | Recruiting Phase 2

• 1 other identifier: HLX10-010-MSI201
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 33

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).

Conditions

MSI-H Solid Malignant Tumor

Outcome Measures

Primary Outcomes (1)

• ORR

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

  up to 2 years

Secondary Outcomes (8)

• ORR

  up to 2 years

• ORR

  up to 2 years

• 6-month OS rate

  from the date of first dose unitl the date of 6-month

• 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

Study Arms (1)

HLX10

EXPERIMENTAL

Drug: HLX10

Interventions

HLX10 DRUG

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.

HLX10

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)):

You may not qualify if:

• 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) \< 50%.
• Presence of peripheral neuropathy with CTCAE v4.03 ≥ grade 2.
• Infection with human immunodeficiency virus (HIV).
• Presence of active pulmonary tuberculosis.
• Previously or currently suffering from interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, seriously injured lung function and other conditions which may interfere with the detection and treatment of suspected drug-related pulmonary toxicity.
• Presence of know active or suspected autoimmune diseases; Patients who have stable status and require no treatment with systemic immunosuppressive therapies are allowed to be enrolled.
• Treatment with live vaccines within 28 days before the first administration of investigational product.
• Subjects requiring treatment with systemic corticosteroids (\> 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.

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (33)

The Second Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230601, China

RECRUITING

Peking University International Hospital

Beijing, Beijing Municipality, 102206, China

RECRUITING

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400042, China

RECRUITING

the 900th Hospital of Joint Logistic Support Force

Fuzhou, Fujian, 35002, China

RECRUITING

Zhongnan Hospital of Wuhan University

Wuhan, Fujian, 430062, China

RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361003, China

RECRUITING

First People's Hospital of Fushan

Fushan, Guangdong, 528010, China

RECRUITING

The First Affiliated Hospital and Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510075, China

RECRUITING

The First Affiliated Hospital (School of Clinical Medicine), Guangdong Pharmaceutical University

Guangzhou, Guangdong, 510080, China

RECRUITING

Affiliated Cancer Hospital & Institute, Guangzhou Medical University

Guangzhou, Guangdong, 510095, China

RECRUITING

the Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

RECRUITING

Affiliated Hospital of Guangdong Medical University

Zhenjiang, Guangdong, 510180, China

RECRUITING

Zhongshan city People's Hospital

Zhongshan, Guangdong, 528404, China

RECRUITING

The Fifth Affiliated Hospital, Sun Yat-sen University

Zhuhai, Guangdong, 519000, China

RECRUITING

The People's Hospital of Guangxi Zhuangzu Autonomous Region

Nanning, Guangxi, 530016, China

RECRUITING

Fourth Hospital of Hebei Medical University,

Shijiazhuang, Hebei, 050011, China

RECRUITING

Harbin Medical University Cancer Hospital,

Harbin, Heilongjiang, 150040, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

RECRUITING

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 200065, China

RECRUITING

The Third Xiangya Hospital, Central South University

Changsha, Hunan, 410013, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410031, China

RECRUITING

Qinhuai Medical District, General Hospital of the eastern theater of the Chinese people's Liberation Army

Nanjing, Jiangsu, 210002, China

RECRUITING

The Second Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, 116023, China

RECRUITING

Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, 110042, China

RECRUITING

Qilu Hospital of Shandong University

Jinan, Shandong, 250012, China

RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

RECRUITING

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

RECRUITING

Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China

Chengdu, Sichuan, 610041, China

RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Tianjin Medical University Cancer Institue and Hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

Yunnan Cancer Hospital/The Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Center

Kunming, Yunnan, 650118, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

Taizhou first people's Hospital

Taizhou, Zhejiang, 318020, China

RECRUITING

Related Publications (2)

• Shukui Qin, Jin Li, Haijun Zhong, et al. Efficacy and safety of HLX10, a novel anti-PD-1 antibody, in patients with previously treated unresectable or metastatic microsatellite instability-high or mismatch repair-deficient solid tumors: A single-arm, multicenter, phase 2 study. Journal of Clinical Oncology 2021 39:15_suppl, 2566-2566

  RESULT

• Qin S, Li J, Zhong H, Jin C, Chen L, Yuan X, Fan Q, Chen K, Cao P, Xiao J, Jiang D, Zhang T, Zhang H, Wang X, Wang W, Han L, Wang Q, Zhu J; Serplulimab-MSI-H Investigators. Serplulimab, a novel anti-PD-1 antibody, in patients with microsatellite instability-high solid tumours: an open-label, single-arm, multicentre, phase II trial. Br J Cancer. 2022 Dec;127(12):2241-2248. doi: 10.1038/s41416-022-02001-3. Epub 2022 Oct 19.

  PMID: 36261583 RESULT

Related Links

• Related Info

Central Study Contacts

ShuKui Qin

CONTACT

86-025-80864362; luolinhua0513@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2019
• First Posted: May 8, 2019
• Study Start: July 15, 2019
• Primary Completion: May 30, 2024
• Study Completion (Estimated): June 30, 2026
• Last Updated: October 28, 2022

Record last verified: 2022-10

Locations

CN (33)