Clinical trial NCT05374226: A Phase 1 Study to Evaluate JS019 in Advanced Solid Tumors or Lymphomas
Official title: A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Recombinant Fully Human Anti-CD39 Monoclonal Antibody JS019 in Patients With Advanced Solid Tumors or Lymphomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumors or Lymphomas
Lead sponsor: Suzhou Kebo Ruijun Biotechnology Co., Ltd
Sponsor class: INDUSTRY
First posted: 2022-05-16
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase 1 clinical study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of JS019 as monotherapy in patients with advanced malignant solid tumors/lymphomas.

The study includes JS019 monotherapy dose escalation, dose expansion and indication expansion stages to investigate the safety, tolerability, pharmacokinetics and preliminary anti-tumor efficacy of JS019 as monotherapy.

Detailed description: Monotherapy Dose Escalation Stage:

In this stage, the safety and tolerability, PK characteristics, immunogenicity and PD of JS019 are investigated. Four dose levels are preset: 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg. The subjects are treated with JS019 by intravenous infusion, once every 3 weeks (Q3W). A treatment cycle is 21 days, and the DLT observation period is 21 days after the first administration. During the study, necessary adjustments may be made to the escalating dose and dosing interval based on the safety, PK and other results obtained.

Monotherapy Dose Expansion Stage:

SMC will select 1\~2 dose levels (dose levels in the monotherapy dose escalation stage or intermediate dose levels) of JS019 as monotherapy. Each dose level includes 6\~9 subjects with advanced malignancies to further evaluate the safety, pharmacokinetics, immunogenicity, pharmacodynamics and efficacy of JS019 as monotherapy, and determine the RP2D of JS019 as monotherapy.

Monotherapy Indication Expansion Stage Based on the determined RP2D of JS019 as monotherapy, 2-4 specific malignancies are selected for indication expansion; about 20-30 patients are included for each indication. It is planned to include expansion cohorts to explore the efficacy and safety of JS019 as monotherapy. The actual cohorts included may be adjusted based on the results of the previous studies.

Eligibility criteria: Inclusion Criteria:

1. Be able to understand and willing to sign the Informed Consent Form;
2. Male or female aged 18\~75 years (included);
3. Patients with pathologically confirmed advanced malignant solid tumors or lymphomas;
4. Failed or unsuitable for standard treatment, received at least one line of systemic treatment;
5. Eastern Cooperative Oncology Group (ECOG) physical fitness score: 0\~1;
6. Expected survival period ≥ 12 weeks;
7. At least one measurable lesion according to criteria RECIST v1.1 or Lugano 2014;

Exclusion Criteria:

1. Patients with known hypersensitivity to the components of JS019;
2. Patients who have received the treatment with anti-CD39 antibodies or inhibitors;
3. Patients who participated in other clinical studies within 4 weeks prior to the first administration of JS019, except patients are in the follow-up period of observational (non-interventional) clinical study or interventional study;
4. Patients who have received major surgery within 4 weeks before the first dose or expected to undergo major surgery during the study (as judged by the investigator) or are in the recovery period from surgery;
5. Patients who have received anti-tumor therapy, such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, or biological therapy, within 4 weeks or 5 half-lives of the therapy (whichever is shorter) prior to the first dose of JS019. Patients who have received traditional Chinese medicine or Chinese patent medicine preparations with anti-tumor indications within 2 weeks before the first dose of JS019. Can accept hormone therapy for non-tumor-related diseases (such as insulin therapy for diabetes and hormone replacement therapy, etc.);
6. Patients who have discontinued immunotherapy due to immune-related AEs.
7. Patients who have used immunosuppressive drugs within 4 weeks prior to the first dose of JS019, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids ≤10 mg/day prednisone or equivalent.

Primary outcomes:
measure: Safety and tolerability
timeFrame: 2 years
measure: Maximum tolerated dose (MTD, if possible) and the recommended phase 2 dose (RP2D)
timeFrame: 2 years
Secondary outcomes:
measure: Pharmacokinetics (PK)
timeFrame: 2 years
measure: Immunogenicity
timeFrame: 2 years
measure: Pharmacodynamics （PD）
timeFrame: 2 years
measure: Objective response rate (ORR)
timeFrame: 2 years
measure: Duration of response (DOR)
timeFrame: 2 years
measure: Disease control rate (DCR)
timeFrame: 2 years
measure: Time to response (TTR)
timeFrame: 2 years
measure: Progression-free survival (PFS)
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years
Other outcomes:
measure: Biomarkers
timeFrame: 2 years
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
References: