Advanced Solid Tumor
Conditions
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.
Interventions
DRUGNBL-028
Intravenous infusion (IV), once every two weeks (one treatment cycle is 4 weeks).
Sponsors
NovaRock Biotherapeutics, Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients ≥18 years old, should have fully understood the study and voluntarily signed an informed consent form. 2. 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. 3. Be able to provide previously well-preserved tumor tissue sections, or agree to undergo tumor tissue biopsy for central laboratory biomarker testing. 4. At least one measurable target lesion according to RECIST 1.1. 5. ECOG performance status of 0 or 1 at screening. 6. Life expectancy ≥3 months. 7. 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). 8. 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
1. Previously received CLDN6-targeted or CD137-targeted treatment. 2. Known uncontrolled central nervous system (CNS) cancer including CNS metastasis, meningeal metastasis, or spinal cord compression. 3. Patients with high risk of bleeding due to tumor invasion of important arteries. 4. Has uncontrolled serous cavity effusion (such as pleural effusion, abdominal effusion, or pericardial effusion, etc) requiring repeated drainage. 5. Has adverse events due to previous anti-tumor treatments that have not yet recovered to ≤Grade 1 according to NCI-CTCAE v5.0; 6. Developed immune-related adverse events (irAE) of grade ≥3 (CTCAE 5.0) with prior immunotherapy 7. Known to exist any other malignant tumor requiring intervention. 8. 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. 9. Have received a live viral vaccine within 4 weeks before the first dose of study drug. 10. Have received immunosuppressive medications within 2 weeks prior to the first dose of study drug. 11. 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. 12. Have received radiation therapy or other localized palliative treatment within 2 weeks before the first dose of study drug. 13. Have undergone major surgery within 4 weeks before the first dose of study drug, or scheduled to have major surgery during the study. 14. Have a history of serious cardiovascular disease. 15. Have active or history of autoimmune diseases. 16. A history of immunodeficiency, including HIV testing positive, or having other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation. 17. Active hepatitis B; hepatitis C infection; syphilis infection, active tuberculosis. 18. Hypersensitive to humanized monoclonal antibody products. 19. Women during lactation or pregnancy. 20. 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. 21. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity（DLT） | 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 | Up to approximately 3 years | adverse events (AEs) and severe adverse events (SAEs) |
| Maximum Tolerated Dose（MTD） of NBL-028 | Up to approximately 1 years | Maximum Tolerated Dose |
| Recommended Phase 2 dose（RP2D） | Up to approximately 1 years | Recommended Phase 2 dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) profile of YBL-006.Assessed by parameter t1/2. | Up to approximately 3 years | Apparent terminal Half-Life |
| anti-drug antibody（ADA） | Up to approximately 3 years | anti-drug antibody titer |
| Overall response rate (ORR).Determined using RECIST v1.1 criteria. | Up to approximately 3 years | Objective response rate |
| Duration of response (DoR) | Up to approximately 3 years | Duration of response |
| Progression free survival（PFS） | Up to approximately 3 years | Progression free survival |
| Disease control rate（DCR） | Up to approximately 3 years | Disease control rate |
| Pharmacokinetic (PK) profile of YBL-006.Assessed by parameter Cmax. | Up to approximately 3 years | Observed maximum concentration |
| Pharmacokinetic (PK) profile of YBL-006.Assessed by parameter Area under curve（AUC）. | Up to approximately 3 years | AUC0-t |
| Pharmacokinetic (PK) profile of YBL-006.Assessed by parameter Tmax. | Up to approximately 3 years | Time to maximum concentration |
Countries
China
Contacts
Primary ContactClinical Trials Information Group officer
Outcome results
None listed