About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
Chemotherapy, biological therapy, immunotherapy, , targeted therapy (including small molecule inhibitor of tyrosine kinase), and other antitumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration; radical radiotherapy, major surgery within 4 weeks prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil drugs such as tegafur, capecitabine, or palliative radiotherapy within 2 weeks prior to initial administration.
Participants who have received prior topoisomerase inhibitor-based ADC therapy
Participants with other prior or concurrent malignancies except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after adequate resection, or other malignancy treated with curative intent with a disease-free interval of at least 3 years
Participants with advanced/ clinically significant lung diseases, such as poorly controlled chronic obstructive pulmonary disease (COPD) and asthma, restrictive lung disease, pulmonary hypertension etc.
Trial design
Sequential
Treatments tested in this trial
BL-M14D1
DrugBL-M14D1 will be administered on D1 every 3 weeks.
Treatment groups
Trial outcomes
Primary outcomes
Assess safety and tolerability of BL-M14D1
SAEs, AESIs, TEAEs, death, TEAEs leading to discontinuation, DLTs, physical examination findings (including ECOG PS), vital sign measurements, standard clinical laboratory parameters, ECG parameters (including the change-from-baseline ECG parameters), and ECHO/MUGA findings
Secondary outcomes
To characterize the PK of BL M14D1, total anti-DLL3 antibody, and payload (Ed-04)
PK Endpoints: Serum concentration of BL-M14D1, total anti-DLL3 antibody, and free payload ED-04 vs time will be utilized, serum PK parameters will include Cmax, Tmax, AUC0-8, AUClast and, if possible, Kel, t1/2, CL, Vz, Vss of BL-M14D1, total anti-DLL-3 antibody, and Ed-04. These PK parameters will be calculated both after the first dose and after multiple doses if applicable.
To investigate the antitumor activity of BL-M14D1
* Tumor response evaluated using RECIST v1.1, ORR, DCR, DoR, TTR, and PFS * OS
Sponsors and contacts
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