A Study of NBL-028 in Patients With Advanced Solid Tumors

Official title

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of NBL-028 in Patients With Advanced Solid Tumors

Overview

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.

Interventions

• Drug NBL-028
  Intravenous infusion (IV), once every two weeks (one treatment cycle is 4 weeks).

Primary outcome measures

• Dose-limiting toxicity（DLT） [Time frame: Up to approximately 1 years]
• 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]
• Maximum Tolerated Dose（MTD） of NBL-028 [Time frame: Up to approximately 1 years]
• Recommended Phase 2 dose（RP2D） [Time frame: Up to approximately 1 years]

Secondary outcome measures (9)

• Overall response rate (ORR).Determined using RECIST v1.1 criteria. [Time frame: Up to approximately 3 years]
• Pharmacokinetic (PK) profile of YBL-006.Assessed by parameter Cmax. [Time frame: Up to approximately 3 years]
• Pharmacokinetic (PK) profile of YBL-006.Assessed by parameter Area under curve（AUC）. [Time frame: Up to approximately 3 years]
• Pharmacokinetic (PK) profile of YBL-006.Assessed by parameter Tmax. [Time frame: Up to approximately 3 years]
• Pharmacokinetic (PK) profile of YBL-006.Assessed by parameter t1/2. [Time frame: Up to approximately 3 years]
• anti-drug antibody（ADA） [Time frame: Up to approximately 3 years]
• Disease control rate（DCR） [Time frame: Up to approximately 3 years]
• Duration of response (DoR) [Time frame: Up to approximately 3 years]
• Progression free survival（PFS） [Time frame: Up to approximately 3 years]

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 CLDN6. 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 1.1.
• 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.
• Have active or serious bacterial, fungal, or viral infection requiring systemic anti-infective treatment within 2 weeks prior to the first dose of study drug.
• Have received radiation therapy or other localized palliative treatment within 2 weeks before the first dose of study drug.
• Have undergone major surgery within 4 weeks before the first dose of study drug, or scheduled to have major surgery during the study.
• Have a history of serious cardiovascular disease.
• Have active or history of autoimmune diseases.
• A history of immunodeficiency, including HIV testing positive, or having other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation.
• Active hepatitis B; hepatitis C infection; syphilis infection, active tuberculosis.
• Hypersensitive to humanized monoclonal antibody products.
• Women during lactation or pregnancy.
• Any male and female patients with fertility who refuse to use effective contraceptive methods throughout the entire trial period and within six months after the last administration.
• Other conditions that, in the opinion of the investigator, may affect the safety or compliance of drug treatment in this study, including but not limited to: psychiatric disorders, any severe or uncontrollable diseases, etc.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• No.896 East Zhongshan Road, Shijiazhuang, Hebei Province, China. — Shijiazhuang

Identifiers

NCT: NCT06223256 · NBL-028-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗