Inclusion Criteria:
1. Signed the informed consent form voluntarily and agreed to follow the trial
requirements. 2. Age ≥18 years. 3. Subject weighs more than 40 kg. 4. Has a life expectancy of ≥3 months. 5. Has documented locally advanced or metastatic SCLC, large cell neuroendocrine cancer
(LCNEC), neuroendocrine prostate cancer (NEPC), high-grade gastrointestinal
neuroendocrine tumors (GI-NET), Merkel cell carcinoma (MCC), or other neuroendocrine
tumors (with neuroendocrine histology ≥10%) 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 subject must have failed at least 1 line of
platinum therapy in the advanced/metastatic setting. No prior topoisomerase
inhibitor-based antibody-drug conjugate (ADC) therapy is permitted. 6. Agree to provide archival tumor samples (FFPE tissue block or slides) from primary
or metastatic sites:
1. In dose escalation and dose finding: archival tissue obtained within 2 years or
FFPE block from fresh biopsy. If no archival tissue is available, a fresh
tissue biopsy is required. 2. 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.
7. Has at least one measurable lesion based on RECIST (Response Evaluation Criteria in
Solid Tumors) V1.1. 8. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1. 9. Toxicity of previous antitumor therapy has returned to Grade ≤1 as defined by NCI
CTCAE V5.0, except for alopecia and endocrinopathies controlled by replacement
therapy. 10. Has no serious cardiac dysfunction and left ventricular ejection fraction ≥50%
11. Has adequate organ function, defined as:
1. Marrow function: Absolute neutrophil count (ANC) ≥1.5×109/L, platelet count
≥100×109/L, hemoglobin (Hb) ≥9.0 g/dL (blood transfusion, platelet transfusion,
erythropoietin (EPO), hematopoiesis agents (such as thrombopoietin [TPO]), and
G-CSF use are not allowed 1 week prior to screening)
2. Hepatic function: Total bilirubin (TBIL) ≤1.5×ULN (≤3×ULN for subjects with
Gilbert's syndrome or liver metastasis at baseline), AST and ALT without liver
metastasis ≤3.0×ULN, AST and ALT with liver metastasis ≤5.0×ULN. 3. Renal function: Creatinine (Cr) clearance ≥60 mL/minute (Cockcroft-Gault
equation)
12. 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. 13. Urine protein ≤2+ or ≤1000 mg/24 hours. 14. Sexually active fertile subjects and their partners must agree to use highly
effective methods of contraception (defined in Appendix D) during the course of the
study and for 7 months after the last dose of study treatment. An additional
contraceptive method, such as a barrier method (eg, condom), is recommended.
15. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at
screening and must be nonlactating. Female subjects 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.
Exclusion Criteria:
1. 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.
2. Subjects who have received prior topoisomerase inhibitor-based ADC therapy. 3. 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. 4. Subjects with history of severe heart disease, such as symptomatic congestive heart
failure (CHF) ≥Grade 2 (CTCAE 5.0), 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. 5. Subjects with prolonged QT interval (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. 6. 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., except for type 1
diabetes, hypothyroidism that can be controlled by standard of care treatment, and
skin diseases that do not require systemic treatment (such as vitiligo, psoriasis)
7. Subjects 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. 8. Subjects with poorly controlled hypertension by 2 types of antihypertensive drugs
(systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg)
9. Subjects with advanced/ clinically significant lung diseases, such as poorly
controlled COPD and asthma, restrictive lung disease, pulmonary hypertension etc.
10. Subjects who have a history of noninfectious interstitial lung disease
(ILD)/pneumonitis that required treatment with steroids, have current
ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging
at screening. 11. Subjects with stroke or transient ischemic attack (TIA) within 6 months before
screening. 12. Subjects 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. 13. Subjects with primary tumors in the central nervous system (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 evidence of new or enlarging
brain metastases and no requirements for corticosteroids 14 days prior to screening.
14. Subjects with pre-existing Grade ≥2 peripheral neuropathy. 15. Subjects 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. 16. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation. 17. Subjects who are receiving treatment with systemic glucocorticoids >10 mg/day
equivalent of prednisone, except for the treatment of chronic obstructive pulmonary
disease, 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. 18. Subjects who have received treatment with anthracyclines with a cumulative dose
exceeding 360 mg/m2. 19. Subjects 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.
20. Subjects with active hepatitis B virus (HBV) infection (positive HBsAg test).
Subjects with chronic inactive HBV infection are eligible if they meet all of the
following criteria:
1. Have a HBV DNA viral load ≤ 500 IU/mL. 2. Have normal AST and ALT, OR if liver metastasis is present, has AST and ALT < 3
× ULN which are not attributed to HBV infection. 3. Are on antiviral treatment, as clinically indicated.
21. Subjects with active hepatitis C virus (HCV) infection (HCV antibody positive and
HCV RNA > the lower limit of detection). Subjects with a positive anti-HCV antibody
are eligible only if PCR is negative for HCV RNA. 22. Subjects with active or latent tuberculosis. 23. Subjects 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.
24. Participated in another clinical trial within 4 weeks prior to first dose of study
treatment. 25. Subjects who are pregnant or breastfeeding, or planning to become pregnant during
the study. 26. Other conditions that the Investigator or Sponsor believes are not suitable for
participating in this clinical trial
