A Clinical Study to Evaluate the Safety and Tolerability of JS012 in Advanced or Metastatic Solid Tumors

A Phase I Clinical Study Evaluating the Safety ,Tolerability, Pharmacokinetics of JS012 in Patients With Advanced or Metastatic Solid Tumors

The purpose of this phase I clinical study was to evaluate the safety and tolerability of JS012 monotherapy and combination with chemotherapy in patients with Advanced or Metastatic Solid Tumors.

Study Overview

• Status: Terminated
• Conditions: Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: JS012; Combination product: JS012 combine with chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yi Ba, M.D.; Phone Number: 8622-23340123-1051; Email: bayi@tjmuch.com
• Study Contact Backup: Name: Ting Deng, M.D.; Phone Number: 8622-23340123-1051; Email: xymcdengting@126.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subjects voluntarily participated in the study with full informed consent and signed written informed consent form;
2. Aged ≥18 years and ≤70 years when the subject signed the informed consent;
3. Locally advanced unresectable or metastatic malignant solid tumors diagnosed histologically ;
4. Provide past tumor samples or fresh tumor tissue biopsy samples;
5. There should be at least one measurable lesion according to RECIST V1.1 evaluation criteria;
6. The expected survival is ≥3 months;
7. The physical status score is 0 or 1 on the Eastern Oncology Collaboration (ECOG) scale;
8. Good organ function;
9. Any adverse events and/or complications resulting from prior treatment, including surgery or radiation therapy, that have been adequately resolved to level 0 or 1 (according to the NATIONAL Cancer Institute Standard for General Terminology of Adverse Events (NCI-CTCAE 5.0) or to the level specified in the inclusion criteria; Any grade of hair loss/pigmentation and other long-term toxicity caused by treatment, except those that are irreversible and do not affect study dosing/compliance and patient safety at the discretion of the investigator;
10. Within 7 days prior to the first dose, women of reproductive age must be confirmed as having a negative serum pregnancy test and consent to use effective contraception during the duration of study drug use and for 90 days after the last dose. Male patients with a female partner of reproductive age agreed to use effective contraception during the study drug use period and for 90 days after the last dose.

Exclusion Criteria:

1. A history of severe allergic reactions to other monoclonal antibodies or to any component of JS012, or to other drugs or excipients involved in the trial protocol ;
2. Prior treatment with drugs or other therapies targeting CLDN18.2;
3. Malignant tumors other than the target tumor within 5 years before the first dose (except for cured cervical carcinoma in situ, basal or squamous cell skin cancer, localized prostate cancer, or breast ductal carcinoma in situ);
4. Pregnant or lactation female patients;
5. History of allogeneic organ transplantation or hematopoietic stem cell transplantation;
6. Presence of uncontrolled or symptomatic active central nervous system (CNS) metastases;
7. Poorly controlled pleural effusion, peritoneal effusion or pericardial effusion (thoracoabdominal drainage frequency ≥1 times/month) ;
8. Clinically significant ileus;
9. Poorly controlled tumor-related pain;
10. BMI less than 17.5 at the time of signing the informed consent, or weight loss >10% in the first 2 months (significant pleural effluents should be considered) or other indicators of severe malnutrition;
11. The following within 6 months prior to the first study dose: myocardial infarction, severe/unstable angina, NYHA class 2 or higher cardiac insufficiency, clinically significant supraventricular or ventricular arrhythmia, and symptomatic congestive heart failure , hypertensive crisis, or hypertensive encephalopathy; patients with known hypertension, coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction <50% must be treated with optimal stabilization as determined by the treating physician medical plan;
12. Received a drug or treatment prohibited by the protocol prior to the first dose;
13. Serious infection (CTC AE> grade 2) occurred within 28 days before the first dose, such as severe pneumonia, bacteremia, infectious complications requiring hospitalization, etc.
14. Active infection;
15. History of autoimmune disease;
16. Idiopathic pulmonary fibrosis, drug-induced pneumonia, machine-induced pneumonia (bronchiolitis obliterans), radioactive pneumonia with clinical symptoms or requiring steroid treatment, active pneumonia, or other moderate to severe lung diseases that seriously affect lung function ;
17. Inability to swallow pills, malabsorption syndrome, or any condition that affects gastrointestinal absorption;
18. The presence of other serious physical or mental disorders or abnormal laboratory tests, or the presence of alcohol or drug abuse, may increase the risk of study participation, affect treatment compliance, or interfere with study results, as well as other patients deemed unsuitable for study participation by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JS012	Drug: JS012; JS012, i.v., q3w
Experimental: JS012 combination with chemotherapy	Combination product: JS012 combine with chemotherapy; JS012 i.v., q3w combine with chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of DLT	The Incidence of dose-limiting toxicity（DLT）	Up to approximately 41 months from first patient in.
Incidence and severity of AE	The incidence and severity of adverse events (AE)	Up to approximately 41 months from first patient in.
Incidence and severity of SAE	The incidence and severity of serious adverse events (SAE)	Up to approximately 41 months from first patient in.
MTD	Determine maximum tolerated dose (MTD, if possible)	Up to approximately 41 months from first patient in.
RP2D	Recommended phase II dose (RP2D) for JS012 monotherapy and combination therapy	Up to approximately 41 months from first patient in.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug concentrations	Drug concentrations in individual subjects at different time points after dosing	Up to approximately 41 months from first patient in.
Cmax	Peak concentration	Up to approximately 41 months from first patient in.
Tmax	Peak time	Up to approximately 41 months from first patient in.
Ctrough	Minimum concentration	Up to approximately 41 months from first patient in.
AUC0-T	Area under the curve from time zero to the time of the t	Up to approximately 41 months from first patient in.
AUC0-INF	Area under the curve from time zero to infinity	Up to approximately 41 months from first patient in.
t1/2	elimination half-life	Up to approximately 41 months from first patient in.
CL	clearance	Up to approximately 41 months from first patient in.
MRT	mean retention time	Up to approximately 41 months from first patient in.
Vss	steady-state apparent volume of distribution (Vss) (if applicable)	Up to approximately 41 months from first patient in.
Css, Max	steady-state peak concentration Degree (Css, Max) (if applicable)	Up to approximately 41 months from first patient in.
Css, min	Steady state minimum observed concentration (if applicable)	Up to approximately 41 months from first patient in.
AUCss	steady-state area under curve (AUCss) (if applicable)	Up to approximately 41 months from first patient in.
Rac	accumulation ratio (Rac) (if applicable)	Up to approximately 41 months from first patient in.
Immunogenicity	Incidence of anti-drug antibody (ADA) and/or neutralizing antibody (Nab), titer of ADA positive samples	Up to approximately 41 months from first patient in.
ADCC	Antibody Dependent cell-mediated cytotoxicity (ADCC)	Up to 21 days from pre-dose of JS012 administration in cycle 1 for each subject in the dose escalation and dose expansion phases
CDC	Complement dependent cytotoxicity(CDC)	Up to 21 days from pre-dose of JS012 administration in cycle 1 for each subject in the dose escalation and dose expansion phases
ORR	Objective response rate (ORR) was assessed based on RECIST V1.1 criteria	Up to approximately 41 months from first patient in.
DOR	Duration of response (DOR) was assessed based on RECIST V1.1 criteria	Up to approximately 41 months from first patient in.
DCR	Disease control rate (DCR) was assessed based on RECIST V1.1 criteria	Up to approximately 41 months from first patient in.
TTR	Time to response (TTR) was assessed based on RECIST V1.1 criteria	Up to approximately 41 months from first patient in.
PFS	Progression-free survival (PFS) was assessed based on RECIST V1.1 criteria	Up to approximately 41 months from first patient in.
OS	Overall survival (OS)	Up to approximately 41 months from first patient in.

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.
• Investigators: Principal Investigator: Yi Ba, M.D., Tianjin Medical University Cancer Institute & Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2022
• Primary Completion (Actual): September 19, 2022
• Study Completion (Actual): September 19, 2022

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: May 19, 2022
• First Posted (Actual): May 24, 2022

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: JS012-001-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
• product manufactured in and exported from the U.S.: No