Clinical Study of JS201 in Patients With Advanced Malignant Tumors

An Open-label, First-in-human, Dose Escalation and Expansion Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of JS201 in Patients With Advanced Malignant Tumors

This is an open label, phase I clinical study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, pharmacodynamic (PD) profile, immunogenicity and preliminary efficacy of JS201 in the patients with advanced malignant tumors who have progression after or during the standard of care, or no effective standard therapeutic regimen. This study is divided into three phases: dose-escalation phase, dose expansion phase, and clinical expansion phase.

Study Overview

• Status: Recruiting
• Conditions: Patients With Advanced Malignant Tumors
• Intervention / Treatment: Drug: JS201

• Study Type: Interventional
• Enrollment (Anticipated): 244
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pan He, Postgraduate; Phone Number: +8615172333540; Email: pan_he@junshipharma.com

Study Locations

• China
  • Guangzhou, China
    • Recruiting
    • Sun Yat-sen University Cancer Center
    • Contact: Li Zhang, Prof; Email: zhangli@sysucc.org.cn
  • Beijing
    • Beijin, Beijing, China, 100000
      • Not yet recruiting
      • Beiijng Cancer Hospital
      • Contact: Ziping Wang, Prof; Email: wangzp2007@126.com
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Not yet recruiting
      • The First Affiliated Hospital of Fujian Medical University
      • Contact: Ning Xu, Prof; Email: drxun@163.com
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Not yet recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Jundong Li, Prof; Email: lijd@sysucc.org.cn
    • Guangzhou, Guangdong, China, 510699
      • Not yet recruiting
      • The First Affiliated Hospital of Guangdong Pharmaceutical University
      • Contact: Xicheng Wang, Prof; Email: 13902400598@126.com
  • Guangong
    • Guangzhou, Guangong, China, 510060
      • Not yet recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Fangjian Zhou, Prof; Email: zhoufj@sysucc.org.cn
  • Hebei
    • Baoding, Hebei, China, 071030
      • Recruiting
      • Affiliated Hospital of Hebei University
      • Contact: Aimin Zang, Prof; Email: booszam@sina.com
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Not yet recruiting
      • Harbin Medical University Cancer Hospital
      • Contact: Yanqiao Zhang, Prof; Email: yanqiaozhang@126.com
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Not yet recruiting
      • Henan Cancer Hospital
      • Contact: Shujun Yang, Prof; Email: nkyang@126.com
    • Zhenzhou, Henan, China, 450000
      • Not yet recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Qingxia Fan, Prof; Email: fqx2243@126.com
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Not yet recruiting
      • Union Hospital Tongji Medical College Huazhong University of Science and Techonoly
      • Contact: Guiling li, Prof
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Not yet recruiting
      • Nanjing Drum Tower Hospital
      • Contact: Hongjian Guo, Prof; Email: gymwpi@126.com
    • Wuxi, Jiangsu, China, 214000
      • Not yet recruiting
      • Affiliated Hospital of Jiangnan University
      • Contact: Yong Mao, Prof; Email: mydoctorwx@aliyun.com
    • Xuzhou, Jiangsu, China, 221009
      • Not yet recruiting
      • Xuzhou Central Hospital
      • Contact: Yong Liu, Prof; Email: lyly.7011@163.com
  • Liaoning
    • Shenyang, Liaoning, China, 110801
      • Not yet recruiting
      • Liaoning Cancer Hospital & Institute
      • Contact: Bin Hu, Prof; Email: hubin556@aliyun.com
  • Shandong
    • Jinan, Shandong, China, 250117
      • Not yet recruiting
      • Shandong Tumor Hospital
      • Contact: Bo Liu, Prof; Email: 15553115688@163.com
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Not yet recruiting
      • Shanghai Pulmonary Hospital
      • Contact: Peng Zhang, Prof
      • Contact: Email: zhangpeng1121@tongji.edu.cn
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Not yet recruiting
      • West China Hospital Sichuan University
      • Contact: Jiyan Liu, Prof; Email: liujiyan1972@163.com
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Not yet recruiting
      • Cancer Hospital of The University of Chinese Academy of Sciences
      • Contact: Yun Fan, Prof; Email: fanyun@zjcc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Understanding and voluntarily signing the informed consent form;
2. Male or female, aged 18 to 70 years (inclusive), for the dose-expansion and clinical expansion parts, aged 18 to 75 years (inclusive);
3. Patients with histologically or cytologically confirmed advanced malignant tumors who have progression after or on the standard of care, or have no effective standard therapeutic regimen;
4. In the clinical expansion stage, patients with advanced cervical cancer, lymphoma, non-small cell lung cancer (NSCLC), gastric cancer, urothelial cancer and other malignant solid tumors diagnosed by histology or cytology were enrolled (the details shown in the full protocol);
5. ECOG PS score: 0~1;
6. Patients with life expectancy ≥12 weeks;
7. At least one measurable lesion per RECIST v1.1 (solid tumors) or 2014 Lugano (lymphoma) criteria;
8. Agree to provide fresh biopsies prior to first dose, or archived samples within two years if there is unpredictable risk of biopsy to the patient（at least 15 fresh biopsy sections or 11 surgical sections). For patients who cannot provide abovementioned sections of tissue samples due to special conditions, it needs to contact with the medical monitor of the sponsor to confirm whether this inclusion criterion can be exempted;

9. Function of vital organs must meet the followings (no blood transfusion or hematopoietic stimulating factor used within 14 days prior to the first dose

   Absolute neutrophil count (ANC) ≥1.5×109/L;

   Platelet (PL) ≥100×109/L;

   Hemoglobin (Hb) ≥ 9 g/dL;

   Total bilirubin (TBIL) ≤1.5 × ULN; if there is hepatic metastasis, total bilirubin ≤2 × ULN; direct bilirubin (dBIL) ≤ 3.0mg/dL in the patients with Gilbert's syndrome;

   Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; or ≤5 × ULN in the patients with hepatic metastasis;

   Serum creatinine (Cr) ≤1.5 × ULN, or calculated creatinine clearance (using Cockcroft -Gault formula) ≥50 mL/min, or 24-hour urine creatinine clearance ≥ 50 mL/min;

   International normalized ratio (INR) ≤1.5 × ULN and activated partial thromboplastin time (aPTT) ≤1.5 × ULN in the patients receiving no anticoagulation therapy;

   QTc interval ≤450 ms for man and ≤470 ms for woman, as calculated using Fridericia's formula;

10. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use a medically recognized contraceptive measure (e.g., intrauterine device IUD, contraceptive or condom) during the study and within 3 months after the end of treatment; the serum HCG test must be negative in the female patients with childbearing potential within 7 days prior to enrollment; and the female patients must be not lactating.

Exclusion criteria

1. Known allergy to any component of JS201;
2. The patients have previously received the TGF-β/TGF-β receptor targeted drugs;
3. Received other investigational product within 4 weeks prior to the first dose of JS201;
4. Accepted major surgery (judged by investigator) or in the recovery period of the surgery within 4 weeks after the first dose of JS201;
5. Antitumor chemotherapy (6 weeks after the last dose of nitrosourea or mitomycin chemotherapy), radiotherapy, hormone therapy, targeted therapy (for small molecular targeted therapy, within 2 weeks prior to the first dose of JS201), immunotherapy (e.g., anti-PD1/PD-L1 and anti-CTLA-4 therapy) or biotherapy (e.g., cell therapy) within 4 weeks prior to the first dose. Local palliative therapy for isolated lesion is acceptable (e.g., local surgery or radiotherapy), if the tumor evaluation is not affected;
6. Use of immunosuppressive drug or immune enhancing drugs (such as thymosin, interferon, interleukin, etc.) within 2 weeks prior to the first dose. However, corticosteroid nasal spray, inhaler or ≤10 mg/day systemic prednisone and equivalent similar products are accepted. Short-term use of systemic corticosteroid therapy with a dose equivalent to prednisone > 10 mg / day (e.g. for the treatment/prevention of contrast medium allergy) with ≤ 3 days is allowed;
7. Previous allogeneic bone marrow transplantation or solid organ transplantation;
8. Live attenuated vaccine within 30 days prior to the first dose is excluded, and inactivated influenza vaccination is allowed;
9. Having other malignant tumor other than the disease investigated within 5 years prior to the first dose. The malignant tumors, including but not limited to sufficiently treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell carcinoma of skin, or ductal carcinoma in situ treated with radical surgery, are eligible;
10. Symptomatic central nervous system (CNS) metastasis requiring intervention (including corticosteroids and antiepileptics). Asymptomatic CNS metastasis previously treated with local therapy is eligible. If the patients confirmed CNS metastasis during screening without any symptoms, and no intervention is required per the standard of care, the eligibility should be determined with the medical monitor of the sponsor;
11. No remission from the toxicity of previous antitumor therapy, i.e., not resolved to baseline, grade 0-1 per NCI-CTCAE v5.0 (except alopecia) or the level specified in the inclusion/exclusion criteria. Patients with irreversible toxicity reasonably expected to be non-aggravated by the study drug (e.g., hearing loss) can participate in this study upon discussion with the medical monitor of the sponsor;
12. Patients have accepted anti PD-1/PD-L1 monoclonal antibody treatment, and immune related adverse events occurred that stop the treatment;
13. Massive pleural effusion, ascites or pericardial effusion with clinical symptoms or requiring symptomatic treatment;
14. Active autoimmune disease requiring systemic therapy (e.g., corticosteroids or immunosuppressants) within 2 years prior to the first dose.

1) The autoimmune diseases include but not limited to systemic lupus erythematosus, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism and multiple sclerosis;

2) Patients with leukoderma or childhood asthma that has been completely relieved and does not need any intervention in adulthood can be enrolled;

3) For the patients combined with rheumatoid arthritis and other joint diseases, Sjogren's syndrome, celiac disease and psoriasis that have been controlled after local therapy, as well as those with positive antinuclear antibody (ANA) and antithyroid antibody, it should be evaluated whether the target organ is involved and systemic treatment is needed, and their enrollment will be determined by investigator;

4) Replacement therapy (e.g., thyroxine, insulin or physiological dose of corticosteroid for adrenal or pituitary insufficiency) will not be regarded as systemic treatment;

5) Patients requiring intermittent use of bronchodilators, inhaled corticosteroids or local injection of corticosteroids for chronic obstructive pulmonary disease (COPD) and asthma can be enrolled.

15. Active infection requiring systematic treatment/antibiotics or intravenous use of systemic anti-infection therapy with 1 week prior to the first dose or use for more than 7 days;

16. History of concurrent serious cerebro- and cardiovascular diseases: ≥grade 3 symptomatic congestive heart failure in accordance with New York Heart Association (NYHA) cardiac function grading system, poorly controlled hypertension or arrhythmia, unstable angina pectoris, myocardial infarction, cerebrovascular accident or transient ischemic attack within 6 months prior to the first doses, or any other arterial thrombosis or embolic event;

17. Presence of active tuberculosis, or interstitial lung disease requiring oral or intravenous steroids or history of pneumonia;

18.Hepatitis (nonalcoholic steatohepatitis and alcoholic/drug-related/autoimmune hepatitis) or cirrhosis;

19. Known positive for human immunodeficiency virus (HIV);

20. Patients with evidence of active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients with HBcAb positive and/or HBsAg positive in the screening stage, if the patients with HBV DNA copy number < 1000 CPS/ml or < 200 IU/ml can be enrolled. HBsAg positive patients must receive antiviral treatment throughout the study period. Patients with positive HCV antibody in the screening stage can be recruited only when the HCV RNA test result is negative;

21. Any other clinical significant diseases or conditions can effect on the compliance with the protocol (e.g., history of psychosis or drug abuse), the signature of the informed consent form (e.g., drug addiction and drug abuse), or is unsuitable to be involved in this clinical trial, which determined by investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JS201	Drug: JS201; JS201 is administered intravenously Q3W at the corresponding dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with DLT (Dose limiting Toxicity)	DLT is defined as any of the specified toxicities evaluated as at least possibly related with the study drug within 21 days after the first dose (NCI-CTCAE v5.0);	21 days after first infusion of study drug
Number of Subjects with adverse event (AE)	An Adverse Event (AE) is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship.	Up to 2 years
Number of Subjects with serious adverse event (SAE)	A Serious Adverse Event (SAE) is an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect	Up to 2 years
Number of Subjects with immune related adverse event (irAE)	IrAE is assessed according to the judgement of investigators	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
anti-drug body (ADA)	incidence of anti-drug body (ADA)	Up to 2 years
peak concentration (Cmax)	Cmax after JS201 administration	Up to 2 years
trough concentration (Ctrough)	Ctrough after JS201 administration	Up to 2 years
area under the plasma drug concentration-time curve (AUC0-t )	AUC0-t after JS201 administration	Up to 2 years
volume of distribution (Vss)	Vss after JS201 administration	Up to 2 years
elimination half-life (t1/2)	t1/2 after JS201 administration	Up to 2 years
clearance rate (CL)	CL after JS201 administration	Up to 2 years
ORR	The efficacy evaluated by the investigator in accordance with RECIST 1.1 criteria (solid tumors) or Lugano criteria (2014, lymphoma), including complete response (CR) and partial response (PR).	Up to 2 years
DOR	DOR is defined as the time from the date of the first documentation of response (confirmed CR or confirmed PR) to the date of the first documentation of PD or death due to any cause, whichever occurs first.	Up to 2 years
DCR	The efficacy evaluated by the investigator per RECIST 1.1 criteria (solid tumors) or Lugano criteria (2014, lymphoma), including CR, PR and stable disease (SD);	Up to 2 years
PFS	PFS is defined as the time from the date of randomization to the earlier of the dates of the first documentation of progressive disease or death due to any cause.	Up to 2 years
OS	OS is defined as the time from the date of randomization to the date of death due to any cause.	Up to 2 years

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2021
• Primary Completion (Anticipated): July 7, 2023
• Study Completion (Anticipated): July 7, 2023

Study Registration Dates

• First Submitted: June 23, 2021
• First Submitted That Met QC Criteria: July 1, 2021
• First Posted (Actual): July 9, 2021

Study Record Updates

• Last Update Posted (Actual): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 1, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: JS201-001-I

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No