Clinical trial NCT03704246: Recombinant Human Anti-PD-1 Monoclonal Antibody HX008 Injection for the Treatment of Advanced Solid Tumors
Official title: A Multicenter, Open and Phase II Clinical Study of HX008 for the Treatment in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Taizhou Hanzhong biomedical co. LTD
Sponsor class: INDUSTRY
First posted: 2018-10-12
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Main 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.

Special inclusion criteria 1 in the Cohort 1.

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.
3. The final cytotoxic drug, radiotherapy, or surgery≥4 weeks away. Special inclusion criteria 1 in the Cohort 2

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.

Main 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.

Primary outcomes:
measure: ORR of HX008 combined with irinotecan and HX008 single drug
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: HX008 safety and tolerability assessed by monitoring AEs
timeFrame: From screening to up to 1 months after the last dose of study drug (up to approximately 2 years)
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 2 years
measure: Immunogenicity
timeFrame: From the first dose of study drug (up to approximately 2 years)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
city: Beijing
country: China
facility: Beijing Yuhe Combination of Chinese Traditional and Western Medicine Recovery Hospital
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
city: Changzhi
country: China
facility: Heping Hospital Affiliated to Changzhi Medical College
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: The affiliated Cancer Hospital of Harbin Medical University
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
city: Shanghai
country: China
facility: Fudan University Cancer Center
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Shenzhen
country: China
facility: Peking university shenzhen hospital
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
city: Taiyuan
country: China
facility: Shanxi Cancer Hospital
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Tianjin
country: China
facility: Tianjin People's Hospital
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Wuhan
country: China
facility: Wuhan Central Hospital
city: Xian
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical College
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
References:
citation: 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.