A Phase 1 Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of BL-M14D1 in Subjects With Locally Advanced or Metastatic Small Cell Lung Cancer and Other Neuroendocrine Neoplasms
The objective of this study is to evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of BL-M14D1 in Subjects with locally Advanced or Metastatic Small Cell Lung Cancer and Other Neuroendocrine Neoplasms
• Signed the informed consent form voluntarily and agreed to follow the trial requirements
• Age ≥18 years
• Participant weighs more than 40 kg
• Life expectancy of ≥3 months
• Documented locally advanced or metastatic SCLC, large cell neuroendocrine cancer of the lung (LCNEC), neuroendocrine prostate cancer (NEPC), poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) or other extrapulmonary neuroendocrine carcinomas (EP-NECs), Merkel cell carcinoma (MCC), or other poorly differentiated and/or high-grade neuroendocrine neoplasms with evidence of DLL3 expression who have failed at least 1 line of standard therapy in the advanced/metastatic setting or are unable to receive standard treatment Notes: For SCLC, the participant must have failed at least 1 line of platinum therapy in the advanced/metastatic setting. No prior topoisomerase inhibitor-based ADC therapy is permitted. In the dose expansion part, Cohort 6 (DLL3-Positive NEN Subgroup): participants will be eligible based on documented positive DLL3 expression.
• Agree to provide archival tumor samples (formalin-fixed paraffin-embedded \[FFPE\] tissue block or 6-12 slides of 5-μm thickness) from primary or metastatic sites:
∙ In dose escalation and dose finding: archival tissue should be obtained within 2 years or FFPE block from fresh biopsy. If no archival tissue is available, a fresh tissue biopsy is required
‣ In dose expansion: an FFPE block from fresh biopsy or archival tissue (within 6 months) is required NOTE: If no archival tissue is available and, a fresh tissue biopsy is clinically contraindicated, please consult the sponsor.
• At least one measurable lesion based on RECIST (Response Evaluation Criteria in Solid Tumors) v1.1
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1
• Toxicity of previous antitumor therapy has returned to Grade ≤1 as defined by National Cancer Institute (NCI) CTCAE v5.0, except for alopecia and endocrinopathies controlled by replacement therapy
⁃ No serious cardiac dysfunction and left ventricular ejection fraction ≥50%
⁃ Adequate organ function, defined as:
• Marrow function: Absolute neutrophil count (ANC) ≥1.5×10\^9/, platelet count
• ≥100×10\^9/L, hemoglobin (Hb) ≥9.0 g/dL (blood transfusion, platelet transfusion, erythropoietin (EPO), hematopoiesis agents (such as thrombopoietin \[TPO\]), and granulocyte colony-stimulating factor \[G-CSF\] use are not allowed 1 week prior to screening)
∙ Hepatic function: Total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN) (≤3×ULN for participants with liver metastasis at baseline), AST and alanine aminotransferase (ALT) without liver metastasis ≤3.0×ULN, AST and ALT with liver metastasis ≤5.0×ULN NOTE: For participants with Gilbert's syndrome, TBIL ≤3.0×ULN in the absence of liver metastases.
∙ Renal function: Creatinine (Cr) clearance ≥60 mL/minute (Cockcroft-Gault equation) or estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] equation)
⁃ Coagulation parameters: International normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (aPTT) ≤1.5×ULN, unless receiving anticoagulation therapy with PT and aPTT levels within the intended therapeutic range
⁃ Urine protein ≤2+ or ≤1000 mg/24 hours
⁃ Sexually active fertile participants and their partners must agree to use highly effective methods of contraception (defined in Appendix D) during the course of the study and after the last dose of study treatment (7 months for women of childbearing potential \[WOCP\] and 4 months for men). An additional contraceptive method, such as a barrier method (eg, condom), is recommended.
⁃ WOCBP must have a negative serum pregnancy test at screening and must be nonlactating. Female participants are considered WOCBP unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \>45 years old in the absence of other biological or physiological causes). In addition, females \<55 years old must have a serum follicle stimulating hormone (FSH) level \>40 mIU/mL to confirm menopause.