Study to Evaluate BL-B01D1 in Patients With Metastatic or Unresectable Non-Small Cell Lung Cancer (NSCLC) and Other Solid Tumors

The objective of this study is to evaluate the safety, tolerability, and efficacy of BL-B01D1 in patients with Metastatic or Unresectable Non-Small Cell Lung Cancer (NSCLC) and Other Solid Tumors.

BL-B01D1-LUNG-101 is a global, multi-center, Phase 1 study to evaluate the safety, tolerability, pharmacokinetics , and initial efficacy of BL-B01D1 in participants with metastatic or unresectable NSCLC and Other Solid Tumors.

This study will be conducted in two different dosing schedules (Cohort A and Cohort B) and three parts (dose escalation, dose finding and dose expansion). Cohort A will be dosed on Day 1 and Day 8 of a continuous 21-day treatment cycle. Cohort B will be dosed on Day 1 of a continuous 21-day treatment cycle. Each Cohort has different dose groups.

Eligibility Criteria:
Inclusion Criteria:

1. Sign informed consent
2. Expected survival \> or = 3months
3. Has histologically documented, incurable, locally advanced or metastatic epithelial origin malignant cancer, priority to include the following tumor types: Non-Small Cell Lung Cancer, HER2- breast cancer, esophageal cancer, Small Cell Lung Cancer, and Nasopharyngeal Cancer
4. Agree to provide a tumor sample
5. Has at least one measurable lesion based on RECIST 1.1
6. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1
7. Toxicity of previous antitumor therapy has returned to level ≤1 as defined by NCI-CTCAE V5.0 (except for asymptomatic laboratory abnormalities such as elevated ALP, hyperuricemia, elevated serum or plasma amylase/lipase, and elevated blood glucose; except for toxicity that the investigator determined to have no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, hypothyroidism stabilized by hormone replacement therapy, etc.)
8. Has no serious cardiac dysfunction, left ventricular ejection fraction ≥50%.
9. Has adequate organ function before registration
10. Coagulation function: international normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (APTT) ≤1.5 ULN
11. Urinary protein ≤2+ or ≤1000mg/24 hours
12. For premenopausal women with childbearing potential, a pregnancy test must be taken within 7 days prior to the start of treatment. Serum or urine pregnancy must be negative and must be non-lactating
13. Must agree to use adequate barrier contraceptive measures during the treatment and 6 months after the end of treatment for all subjects (regardless of gender)

Exclusion Criteria:

1. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy and other anti-tumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration
2. Subjects with history of severe heart disease
3. Active autoimmune diseases and inflammatory diseases
4. Other malignant tumors were diagnosed within 5 years
5. Subjects with poorly controlled hypertension
6. Subjects have Grade 3 lung disease or a history of interstitial lung disease
7. Unstable thrombotic events such as deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring therapeutic intervention within the previous 6 months before screening
8. Symptoms of active central nervous system metastasis
9. Subjects who have a history of allergies to recombinant humanized antibodies or human mouse chimeric antibodies or any of the components of BL-B01D1
10. Subjects have a history of autologous or allogeneic stem cell transplantation
11. Known HIV, active tuberculosis, active Hepatitis B virus infection or active Hepatitis C virus infection
12. Subjects with active infections requiring systemic treatment
13. Participated in another clinical trial within 4 weeks prior to participating in the study
14. Other conditions that the investigator believes that it is not suitable for participating in this clinical trial
15. Subjects with prolonged QT interval (QTc \>470 msec), complete left bundle branch block, Grade 3 atrioventricular block
16. Has received treatment with anthracyclines with a cumulative dose exceeding 360 mg/m2