Clinical trial NCT05388279: A Clinical Study to Evaluate the Safety and Tolerability of JS012 in Advanced or Metastatic Solid Tumors
Official title: A Phase I Clinical Study Evaluating the Safety ,Tolerability, Pharmacokinetics of JS012 in Patients With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
Lead sponsor: Shanghai Junshi Bioscience Co., Ltd.
Sponsor class: OTHER
First posted: 2022-05-24
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Sequential
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of DLT
timeFrame: Up to approximately 41 months from first patient in.
measure: Incidence and severity of AE
timeFrame: Up to approximately 41 months from first patient in.
measure: Incidence and severity of SAE
timeFrame: Up to approximately 41 months from first patient in.
measure: MTD
timeFrame: Up to approximately 41 months from first patient in.
measure: RP2D
timeFrame: Up to approximately 41 months from first patient in.
Secondary outcomes:
measure: Drug concentrations
timeFrame: Up to approximately 41 months from first patient in.
measure: Cmax
timeFrame: Up to approximately 41 months from first patient in.
measure: Tmax
timeFrame: Up to approximately 41 months from first patient in.
measure: Ctrough
timeFrame: Up to approximately 41 months from first patient in.
measure: AUC0-T
timeFrame: Up to approximately 41 months from first patient in.
measure: AUC0-INF
timeFrame: Up to approximately 41 months from first patient in.
measure: t1/2
timeFrame: Up to approximately 41 months from first patient in.
measure: CL
timeFrame: Up to approximately 41 months from first patient in.
measure: MRT
timeFrame: Up to approximately 41 months from first patient in.
measure: Vss
timeFrame: Up to approximately 41 months from first patient in.
measure: Css, Max
timeFrame: Up to approximately 41 months from first patient in.
measure: Css, min
timeFrame: Up to approximately 41 months from first patient in.
measure: AUCss
timeFrame: Up to approximately 41 months from first patient in.
measure: Rac
timeFrame: Up to approximately 41 months from first patient in.
measure: Immunogenicity
timeFrame: Up to approximately 41 months from first patient in.
measure: ADCC
timeFrame: Up to 21 days from pre-dose of JS012 administration in cycle 1 for each subject in the dose escalation and dose expansion phases
measure: CDC
timeFrame: Up to 21 days from pre-dose of JS012 administration in cycle 1 for each subject in the dose escalation and dose expansion phases
measure: ORR
timeFrame: Up to approximately 41 months from first patient in.
measure: DOR
timeFrame: Up to approximately 41 months from first patient in.
measure: DCR
timeFrame: Up to approximately 41 months from first patient in.
measure: TTR
timeFrame: Up to approximately 41 months from first patient in.
measure: PFS
timeFrame: Up to approximately 41 months from first patient in.
measure: OS
timeFrame: Up to approximately 41 months from first patient in.
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Yi Ba, M.D.
role: PRINCIPAL_INVESTIGATOR
References: