Evaluating BL-M14D1 in Subjects With Locally Advanced or Metastatic Small Cell Lung Cancer and Neuroendocrine Tumors

Exclusion Criteria28

• 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
• Concomitant use of strong inhibitors and inducers of any CYP enzyme or transporter system within 2 weeks prior to the first administration and throughout all parts of the study
• Participants with history of severe heart disease, such as symptomatic (CHF) ≥Grade 2 (CTCAE v5.0), New York Heart Association (NYHA) ≥Grade 2 heart failure at any time, history of myocardial infarction or unstable angina pectoris within 6 months before enrollment
• Participants with prolonged QT interval corrected (Fridericia formula (QTcF \>470 msec), complete left bundle branch block, Grade 3 atrioventricular block, or a history of additional risk factors for Torsades de Pointes (TdP); eg, heart failure as defined in Exclusion Criterion 4, chronic or recurrent hypokalemia that requires medical intervention, congenital long QT syndrome, family history of long QT syndrome) or any current concomitant medication known to prolong the QT/QTc interval or cause TdP.
• Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease, and Hashimoto's thyroiditis, etc. Participants with skin diseases that do not require systemic treatment (such as vitiligo, psoriasis), well-controlled type 1 diabetes, or hypothyroidism are permitted. For autoimmune conditions that are active but stable and low grade on systemic therapy, discussion with the medical monitor is required prior to screening.
• 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 poorly controlled hypertension by 2 types of antihypertensive drugs (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg)
• Participants with advanced/ clinically significant lung diseases, such as poorly controlled chronic obstructive pulmonary disease (COPD) and asthma, restrictive lung disease, pulmonary hypertension etc.
• Participants who have a history of noninfectious ILD/pneumonitis that required treatment with steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Participants with stroke or transient ischemic attack (TIA) within 6 months before screening
• Participants with a thromboembolic event (eg, deep vein thrombosis \[DVT\] or pulmonary embolism \[PE\]) within 6 months before screening except for those who are clinically stable and receiving treatment with adequate anticoagulant therapy for at least 3 weeks before screening
• Participants with primary neoplasms in the (CNS), active or untreated CNS metastases or carcinomatous meningitis should be excluded. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks and have no radiological evidence of new or enlarging brain metastases and no requirements for corticosteroids 14 days prior to screening.
• Participants with preexisting Grade ≥2 peripheral neuropathy
• Participants who have a history of anaphylaxis or severe hypersensitivity to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL-M14D1
• Previous organ transplantation or allogeneic hematopoietic stem cell transplantation
• Participants who are receiving treatment with systemic glucocorticoids \>10 mg/day equivalent of prednisone, except for the treatment of COPD, antiemetic, infusion reactions; however, treatment with low dose glucocorticoids (≤10 mg/day equivalent of prednisone) is permitted. The use of topical, inhaled, and locally injected steroids is permitted
• Participants with known human immunodeficiency virus infection (HIV Ab positive). Subjects are allowed to participate if all of the following criteria are met: (1) Undetectable HIV RNA and CD4 count ≥350 cells/μL at Screening, (2) No AIDS-defining opportunistic infection within 12 months prior to screening, (3) On stable antiretroviral therapy (ART) for at least 4 weeks prior to Screening with projected continuation of ART as clinically indicated while on the study
• Participants with active hepatitis B virus (HBV) infection (positive HBsAg test). Participants with chronic inactive HBV infection are eligible if they meet all of the following criteria:
• Have a HBV DNA viral load ≤ 500 IU/mL
• Normal AST and ALT, OR if liver metastasis is present, has AST and ALT \< 3 × ULN which are not attributed to HIV infection
• Are on antiviral treatment, as clinically indicated.
• Participants with active hepatitis C virus (HCV) infection (HCV antibody positive and HCV RNA \> the lower limit of detection). Participants with a positive anti-HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
• Participants with active or latent tuberculosis
• Participants with active infections requiring IV antibiotic, antiviral, or antifungal treatment, such as severe pneumonia, bacteremia, sepsis, etc., within 1 week prior to first dose of study treatment. Subjects on stable oral antimicrobials with no clinical or laboratory evidence of active infection are eligible.
• Participated in another clinical trial within 4 weeks prior to first dose of study treatment
• Participants who are pregnant or breastfeeding, or planning to become pregnant during the study
• Other conditions that the Investigator or Sponsor believes are not suitable for participating in this clinical trial