A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of NBL-028 in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- NBL-028
- Conditions
- Advanced Solid Tumor
- Sponsor
- NovaRock Biotherapeutics, Ltd
- Enrollment
- 270
- Locations
- 1
- Primary Endpoint
- Dose-limiting toxicity（DLT）
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a multi-center, single agent study conducted in patients with advanced solid tumor types known to express Claudin 6 (CLDN6) for whom standard of care therapies are not available, are no longer effective, or not tolerated. This study consists two stages: dose-escalating and dose-expansion.
Dose escalation will be guided by the Bayesian optimal interval (BOIN) design including accelerated titration to determine the maximum tolerated dose (MTD) of NBL-028. Dose expansion - Additional patients (no more than 200) will be enrolled at the recommended dose or multiple doses (if necessary) determined in the dose escalation stage. Sponsor may elect to enroll specific tumor types into four cohorts.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients ≥18 years old, should have fully understood the study and voluntarily signed an informed consent form.
- •Patients with pathologically diagnosed advanced solid tumors with positive expression of CLDN
- •Stage I: Patients have failed or cannot tolerate standard of care, or without standard treatment; Stage Ⅱ: Previously treated advanced solid tumors.
- •Be able to provide previously well-preserved tumor tissue sections, or agree to undergo tumor tissue biopsy for central laboratory biomarker testing.
- •At least one measurable target lesion according to RECIST 1.
- •ECOG performance status of 0 or 1 at screening.
- •Life expectancy ≥3 months.
- •Adequate organ function within 7 days prior to the first dose defined as: Absolute neutrophil count (ANC) ≥1.5×10\^9/L; Platelet count (PLT) ≥100×10\^9/L;. Hemoglobin (HGB) ≥90 g/L; Serum creatinine ≤ 1.5 × ULN or Calculated creatinine clearance (CrCl) (Cockcroft-Gault formula) ≥50 mL/min; Total bilirubin (TBIL) ≤1.5×ULN (≤3×ULN when patients with Gilbert's disease); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN if liver involvement is known).
- •Serum pregnancy test for women of childbearing potential (WOCBP) is negative within 7 days prior to the first dose of the investigational drug. The patient and his/her spouse must agree to use adequate contraception from signing of informed consent form (ICF) to 3 months after the last dose, during which women should be non-lactating and men should refrain from donating sperm.
Exclusion Criteria
- •Previously received CLDN6-targeted or CD137-targeted treatment.
- •Known uncontrolled central nervous system (CNS) cancer including CNS metastasis, meningeal metastasis, or spinal cord compression.
- •Patients with high risk of bleeding due to tumor invasion of important arteries.
- •Has uncontrolled serous cavity effusion (such as pleural effusion, abdominal effusion, or pericardial effusion, etc) requiring repeated drainage.
- •Has adverse events due to previous anti-tumor treatments that have not yet recovered to ≤Grade 1 according to NCI-CTCAE v5.0;
- •Developed immune-related adverse events (irAE) of grade ≥3 (CTCAE 5.0) with prior immunotherapy
- •Known to exist any other malignant tumor requiring intervention.
- •Have received anti-tumor treatments (such as chemotherapy, targeted therapy, biological therapy, etc.) or any other investigational drugs or treatments within 4 weeks or 5 half-lives, whichever is shorter.
- •Have received a live viral vaccine within 4 weeks before the first dose of study drug.
- •Have received immunosuppressive medications within 2 weeks prior to the first dose of study drug.
Arms & Interventions
NBL-028
Patients will be treated with NBL-028 at starting dose of 0.01 mg/kg in dose escalation stage. In dose expansion stage, patients will be treated with NBL-028 at the recommended dose or multiple doses (if necessary) determined in the dose escalation stage.
Intervention: NBL-028
Outcomes
Primary Outcomes
Dose-limiting toxicity（DLT）
Time Frame: Up to approximately 1 years
Dose-limiting toxicity
Incidence and severity of adverse events (AE) and serious adverse events (SAE) Incidence, nature, and severity of adverse events will be graded according to the NCI CTCAE v5.0
Time Frame: Up to approximately 3 years
adverse events (AEs) and severe adverse events (SAEs)
Maximum Tolerated Dose（MTD） of NBL-028
Time Frame: Up to approximately 1 years
Maximum Tolerated Dose
Recommended Phase 2 dose（RP2D）
Time Frame: Up to approximately 1 years
Recommended Phase 2 dose
Secondary Outcomes
- Overall response rate (ORR).Determined using RECIST v1.1 criteria.(Up to approximately 3 years)
- Pharmacokinetic (PK) profile of YBL-006.Assessed by parameter Cmax.(Up to approximately 3 years)
- Pharmacokinetic (PK) profile of YBL-006.Assessed by parameter Area under curve（AUC）.(Up to approximately 3 years)
- Pharmacokinetic (PK) profile of YBL-006.Assessed by parameter Tmax.(Up to approximately 3 years)
- Pharmacokinetic (PK) profile of YBL-006.Assessed by parameter t1/2.(Up to approximately 3 years)
- anti-drug antibody（ADA）(Up to approximately 3 years)
- Disease control rate（DCR）(Up to approximately 3 years)
- Duration of response (DoR)(Up to approximately 3 years)
- Progression free survival（PFS）(Up to approximately 3 years)