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

Advanced or Metastatic Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05388279
• Other study ID #: JS012-001-I
• Status: Terminated
• Phase: Phase 1
• Start date: April 28, 2022
• Est. completion date: September 19, 2022

Study information

• Verified date: March 2023
• Source: Shanghai Junshi Bioscience Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: September 19, 2022
• Est. primary completion date: September 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• JS012
JS012, i.v., q3w

Combination Product:
• JS012 combine with chemotherapy
JS012 i.v., q3w combine with chemotherapy

Locations

Country	Name	City	State
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Junshi Bioscience Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of DLT	The Incidence of dose-limiting toxicity(DLT)	Up to approximately 41 months from first patient in.
Primary	Incidence and severity of AE	The incidence and severity of adverse events (AE)	Up to approximately 41 months from first patient in.
Primary	Incidence and severity of SAE	The incidence and severity of serious adverse events (SAE)	Up to approximately 41 months from first patient in.
Primary	MTD	Determine maximum tolerated dose (MTD, if possible)	Up to approximately 41 months from first patient in.
Primary	RP2D	Recommended phase II dose (RP2D) for JS012 monotherapy and combination therapy	Up to approximately 41 months from first patient in.
Secondary	Drug concentrations	Drug concentrations in individual subjects at different time points after dosing	Up to approximately 41 months from first patient in.
Secondary	Cmax	Peak concentration	Up to approximately 41 months from first patient in.
Secondary	Tmax	Peak time	Up to approximately 41 months from first patient in.
Secondary	Ctrough	Minimum concentration	Up to approximately 41 months from first patient in.
Secondary	AUC0-T	Area under the curve from time zero to the time of the t	Up to approximately 41 months from first patient in.
Secondary	AUC0-INF	Area under the curve from time zero to infinity	Up to approximately 41 months from first patient in.
Secondary	t1/2	elimination half-life	Up to approximately 41 months from first patient in.
Secondary	CL	clearance	Up to approximately 41 months from first patient in.
Secondary	MRT	mean retention time	Up to approximately 41 months from first patient in.
Secondary	Vss	steady-state apparent volume of distribution (Vss) (if applicable)	Up to approximately 41 months from first patient in.
Secondary	Css, Max	steady-state peak concentration Degree (Css, Max) (if applicable)	Up to approximately 41 months from first patient in.
Secondary	Css, min	Steady state minimum observed concentration (if applicable)	Up to approximately 41 months from first patient in.
Secondary	AUCss	steady-state area under curve (AUCss) (if applicable)	Up to approximately 41 months from first patient in.
Secondary	Rac	accumulation ratio (Rac) (if applicable)	Up to approximately 41 months from first patient in.
Secondary	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.
Secondary	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
Secondary	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
Secondary	ORR	Objective response rate (ORR) was assessed based on RECIST V1.1 criteria	Up to approximately 41 months from first patient in.
Secondary	DOR	Duration of response (DOR) was assessed based on RECIST V1.1 criteria	Up to approximately 41 months from first patient in.
Secondary	DCR	Disease control rate (DCR) was assessed based on RECIST V1.1 criteria	Up to approximately 41 months from first patient in.
Secondary	TTR	Time to response (TTR) was assessed based on RECIST V1.1 criteria	Up to approximately 41 months from first patient in.
Secondary	PFS	Progression-free survival (PFS) was assessed based on RECIST V1.1 criteria	Up to approximately 41 months from first patient in.
Secondary	OS	Overall survival (OS)	Up to approximately 41 months from first patient in.