Recombinant Human Anti-PD-1 Monoclonal Antibody HX008 Injection for the Treatment of Advanced Solid Tumors

NCT ID: NCT03704246

Last Updated: 2021-03-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-30
• Study Completion Date: 2021-03-30

Brief Summary

In this study, patients of advanced gastric adenocarcinoma with failed first-line chemotherapy-line or advanced mismatched repair deficient (dMMR) or microsatellite instability-high (MSI-H) advanced solid carcinoma will be treated with HX008 combined with irinotecan and HX008 monotherapy There will be two cohorts in this study: Cohort 1 and Cohort 2. For Cohort 1, advanced gastric adenocarcinoma with failed first-line chemotherapy-line cancer participants, who had failed or were unable to tolerate first line chemotherapy with platinum-based or fluorouracil regimens. For Cohort 2, advanced solid tumor participants, who are required to have been previously treated with at least one line of systemic standard of care therapy.

Detailed Description

Cohort 1:

Currently, no PD-1 antibody against gastric cancer have been approved in China, and there are many patients with gastric cancer in China, so effective, low-toxicity and affordable treatment is urgently needed. This study aims to investigate the efficacy of combined application of recombinant human anti-PD-1 monoclonal antibody (HX008) and irinotecan in patients with locally advanced or metastatic gastric cancer (including gastric esophageal junction cancer) ,thus providing a better treatment for Chinese patients with gastric cancer.Advanced gastric adenocarcinoma with failed first-line chemotherapy-line cancer participants, who had failed or were unable to tolerate first line chemotherapy with platinum-based or fluorouracil regimens are needed.

Cohort 2:

Later-line therapies after failure of standard treatments for advanced solid cancer patients are limited. Mismatch repair (MMR) deficiency or microsatellite instability-high (MSI-H) played a role of positive predictive factor, which had been documented after the pembrolizumab and nivolumab trial were reported, for PD-1 blockade monotherapy in patients with advanced solid carcinomas.

In this study, patients with previously-treated locally-advanced or metastatic mismatched repair deficient (dMMR) or microsatellite instability-high (MSI-H) advanced solid tumors will be treated with HX008 monotherapy.Advanced solid tumor participants, who are required to have been previously treated with at least one line of systemic standard of care therapy are needed.

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Anti-PD-1

Anti-PD-1 monoclonal antibody HX008 injection with a dose of 200mg (intravenous infusion, every 3 weeks)

Group Type: OTHER

Anti-PD-1 monoclonal antibody

Intervention Type: DRUG

HX008 is a monoclonal antibody drug which is intravenous drip at a dose of 200mg.

Interventions

Anti-PD-1 monoclonal antibody

HX008 is a monoclonal antibody drug which is intravenous drip at a dose of 200mg.

Intervention Type: DRUG

Other Intervention Names

HX008

Eligibility Criteria

Inclusion Criteria

1. Subject is male or female; ≥ 18 and ≤ 75 years of age for cohort 1 and ≥ 18 years of age for cohort 2 on the day of signing informed consent, and subject has voluntarily agreed to participate by giving written informed consent.

2. Subjects must have a histopathological diagnosis of any locally advanced or metastatic solid tumor, Subjects must have failed established standard medical anti-cancer therapies ( have disease progression after the therapies or be intolerant to the therapies) or Subjects refuse to standard therapies, or no effective treatment.

3. Subject must have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

4. Measurable disease as defined by RECIST v1.1.

5. Life expectancy ≥ 12 weeks.

6. Subject must have adequate hematologic and organ function.

7. Asymptomatic patients with Central Nervous System (CNS) metastasis or asymptomatic brain metastasis after treatment shall undergo computed tomography (CT) or magnetic resonance imaging (MRI) for no disease progression, stable for at least 3 months and no steroid treatment for at least 4 weeks.

8. Male subjects and female subjects should agree to take effective contraception from the date of signing the informed consent form until 3 months after the last administration.

1. Locally advanced or metastatic gastric adenocarcinoma (including gastric esophageal junction cancer) diagnosed histologically or cytologically.

2. Participants who had previously received a platinum-based or fluorouracil based first-line chemotherapy failed or could not tolerate.

1.Advanced malignant solid tumors confirmed by histology or cytology and confirmed as msi-h or dMMR by the central laboratory designated by the sponsor.

2.Participants must have received or not tolerated a first-line anti-tumor drug regimen.

Exclusion Criteria

1. Participants with other malignant tumors within 5 years before enrollment, excluding cured cervical carcinoma in situ and cured basal cell carcinoma of the skin.

2. Subject Is currently participating and receiving study therapy or has participated in a study of an investigational agent and receive study therapy within 28 days of the first dose of study drug.

3. Subject has not recovered to CTCAE Grade 1 or better from the adverse events due to cancer therapeutics administered.

4. Subject who had received anti-PD-1, PD-L1-,CTLA-4 monoclonal therapy, etc.

5. Subjects with active, or pre-existing, autoimmune diseases that may recur.

6. Systemic corticosteroids should be administered within 14 days before initial administration or during the study.

7. Subjects with active gastrointestinal ulcer, incomplete intestinal obstruction, active gastrointestinal hemorrhage and perforation.

8. Subjects with existing interstitial lung or pneumonia, pulmonary fibrosis, acute pulmonary disease, radioactive pneumonia;

9. Subjects with Uncontrollable and stable systemic diseases, such as cardiovascular and cerebrovascular diseases, diabetes, hypertension and tuberculosis.

10. Subjects with a history of infection with human immunodeficiency virus, or have other acquired or congenital immune deficiency diseases, or have a history of organ transplantation or stem cell transplantation.

11. Subject is positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active hepatitis B (HBV surface antigen positive and HBV DNA ≥ 500 copies/ml)or hepatitis C or tuberculosis (HCV antibody positive).

12. Subjects with severe infection within 4 weeks before first administration, or those with active infection within 2 weeks before administration or intravenous antibiotic treatment.

13. Subjects who have been previously known to have severe allergic reactions to macromolecules/monoclonal antibodies or to any of the test drug components (CTCAE ≥Grade 3).

14. Participated in clinical trials of other drugs within 4 weeks before the first administration (subject to the use of the tested drugs).

15. Subjects with alcohol dependence or a history of drug abuse or drug abuse within one year.

16. Subjects with a clear history of neurological or mental disorders, such as epilepsy, dementia, poor compliance, or peripheral nervous system disorders;

17. Subjects with symptomatic brain metastases.

18. Women who are pregnant or lactating.

19. Subjects were not fit for other reasons concluded by the researchers.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taizhou Hanzhong biomedical co. LTD

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Affiliated Hospital of Hebei University

Baoding, , China

Beijing Yuhe Combination of Chinese Traditional and Western Medicine Recovery Hospital

Beijing, , China

The First Affiliated Hospital of Bengbu Medical College

Bengbu, , China

Hunan Cancer Hospital

Changsha, , China

Xiangya Hospital, Central South University

Changsha, , China

Heping Hospital Affiliated to Changzhi Medical College

Changzhi, , China

Fujian Cancer Hospital

Fuzhou, , China

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, , China

Zhejiang Cancer Hospital

Hangzhou, , China

The affiliated Cancer Hospital of Harbin Medical University

Harbin, , China

Anhui Provincial Cancer Hospital

Hefei, , China

Shandong Cancer Hospital

Jinan, , China

Jiangsu Provincial People's Hospital

Nanjing, , China

Guangxi Medical University Cancer Hospital

Nanning, , China

Fudan University Cancer Center

Shanghai, , China

Liaoning Cancer Hospital

Shenyang, , China

The First Hospital of China Medical University

Shenyang, , China

Peking university shenzhen hospital

Shenzhen, , China

The Fourth Hospital of Hebei Medical University

Shijiazhuang, , China

The Second Affiliated Hospital of Soochow University

Suzhou, , China

Shanxi Cancer Hospital

Taiyuan, , China

Tianjin Cancer Hospital

Tianjin, , China

Tianjin People's Hospital

Tianjin, , China

Hubei Cancer Hospital

Wuhan, , China

Wuhan Central Hospital

Wuhan, , China

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, , China

The First Affiliated Hospital of Xinxiang Medical College

Xinxiang, , China

Henan Cancer Hospital

Zhengzhou, , China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, , China

Countries

China

References

Zhang B, Song Y, Luo S, Yin X, Li E, Wang H, He Y, Liu Z, Fan Q, Liang X, Shu Y, Liu Y, Xu N, Zhang S, Zhuang Z, Zhang J, Kou X, Wang F, Zhu X, Zeng S, Wang K, Zhong H, Li S, Bai Y, Yu J, Dou Y, Ma T, Liu Q, Huang J. Pucotenlimab in patients with advanced mismatch repair-deficient or microsatellite instability-high solid tumors: A multicenter phase 2 study. Cell Rep Med. 2023 Dec 19;4(12):101301. doi: 10.1016/j.xcrm.2023.101301. Epub 2023 Nov 27.

Reference Type: DERIVED

PMID: 38016482 (View on PubMed)

Song Y, Li N, Li Q, Liang X, Zhang S, Fan Q, Yin X, Zhuang Z, Liu Y, Zhang J, Kou X, Zhong H, Wang X, Dou Y, Huang J. HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric or gastroesophageal junction cancer: a multicenter, single-arm phase II trial. J Immunother Cancer. 2020 Oct;8(2):e001279. doi: 10.1136/jitc-2020-001279.

Reference Type: DERIVED

PMID: 33060149 (View on PubMed)

Other Identifiers

HX008-II-02

Identifier Type: -

Identifier Source: org_study_id