A Study of BL-B01D1, SI-B003 and BL-B01D1+SI-B003 in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Other Solid Tumors

Inclusion Criteria:

1. All subjects voluntarily participated in the study and signed informed consent.

2. Male or female aged ≥18 years and ≤75 years.

3. Expected survival time ≥3 months.

4. ECOG 0-1.

5. Patients with recurrent or metastatic head and neck squamous cell carcinoma (non-nasopharyngeal carcinoma) confirmed by histopathology and/or cytology:

6. Cohort_A, B, and Cohort_C Stage I patients who had failed or were intolerant to 1 or more lines of systemic therapy for recurrent or metastatic HNSCC (non-nasopharyngeal carcinoma);

7. Cohort_C Stage II patients who had not received any previous systemic antitumortherapy (other than induction chemotherapy, neoadjuvant, or adjuvant therapy)for recurrent or metastatic HNSCC (non-nasopharyngeal); Treatment failure wasdefined as disease progression during or after systemic antitumor therapy. Intolerance refers to the refusal of patients to continue the original regimen dueto grade 3-4 adverse reactions after receiving standard treatment. Note: Recurrence or disease progression within 6 months after the last chemotherapyof multimodal therapy was considered as the first line of treatment.

8. Consent to provide archival tumor tissue specimens (10-12 unstained sections (anti-slip) surgical specimens (thickness 4-5μm)) or fresh tissue samples fromprimary or metastatic lesions within 3 years. If participants cannot provide tumortissue samples, they can be enrolled if they meet other inclusion and exclusioncriteria after the evaluation of the investigator.

9. Must have at least one measurable lesion according to RECIST v1.1 definition;Lesions that had been previously treated with radiation could be included in ameasurable lesion only if there was definite disease progression after radiationtherapy.

10. No blood transfusions and no use of cell growth factors and/or platelet-raisingdrugs during the 14 days prior to the screening period must be allowed, and theorgan function level must meet the following criteria:

11. Blood routine: hemoglobin (HGB) ≥ 90g/L; Absolute neutrophil count (NEUT) ≥ 1.5×10 9 /L; Platelet count (PLT) ≥ 100×10 9 /L;

12. Renal function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50mL/min (according to Cockcroft and Gault formula).

13. Liver function: total bilirubin (TBIL≤1.5 ULN), alanine aminotransferase (ALT)and aspartate aminotransferase (AST) were all ≤2.5 ULN, and AST and ALT wereboth ≤5.0 ULN when liver metastasis was present;

14. coagulation function: international normalized ratio (INR) ≤1.5 and activatedpartial thromboplastin time (APTT) ≤1.5ULN;

15. no severe cardiac dysfunction with left ventricular ejection fraction ≥50%;

16. proteinuria ≤2+ or ≤1000mg/24h.

17. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined byNCI-CTCAE v5.0 (except for asymptomatic laboratory abnormalities such as ALPelevation, hyperuricemia, and hyperglycemia, as judged by the investigator, andtoxicity without safety risk, such as alopecia, grade 2 peripheral neurotoxicity, ordecreased hemoglobin ≥90g/L, as judged by the investigator).

18. For premenopausal women with childbearing potential, a pregnancy test must beperformed within 7 days before the start of treatment, the serum or urine pregnancytest must be negative, and the patient must not be lactating; All enrolled patientsshould take adequate barrier contraception during the whole treatment cycle and for 6 months after the end of treatment.

Exclusion Criteria:

1. Prior treatment with an ADC drug with a topoisomerase I inhibitor as a toxin.

2. Antineoplastic therapy, including chemotherapy, biologic therapy, immunotherapy,definitive radiotherapy, major surgery (investigator-defined), or targeted therapy (including small-molecule tyrosine kinase inhibitors), has been administered within 4 weeks or 5 half-life cycles (whichever is shorter) before the first dose; Oralfluorouracil drugs such as S-1, capecitabine, or palliative radiotherapy within 2weeks before the first dose.

3. Non-squamous cell tissue confirmed by histopathology and/or cytology must beexcluded.

4. Cohort_C Stage II patients who had received any previous systemic therapy forrecurrent or metastatic HNSCC (other than induction chemotherapy, adjuvant orneoadjuvant therapy) were excluded.

5. Cohort_C with a history of immunotherapy and grade ≥3 irAE or grade ≥2immune-related myocarditis, excluded.

6. Cohort_C cohort_c who had received immunomodulatory drugs (including but not limitedto thymosin, interleukin-2, interferon, etc.) within 14 days before the first doseof study drug was excluded.

7. Systemic corticosteroids (> 10mg/ day of prednisone, or the equivalent of anothercorticosteroid) are required within 2 weeks before the first dose of the study dose;Exceptions were inhaled or topical corticosteroids or physiological replacementdoses of corticosteroids for adrenal insufficiency.

8. A history of immunotherapy with grade ≥3 irAE or grade ≥2 immune-related myocarditismust be excluded.

9. A history of severe cardiovascular and cerebrovascular diseases, including but notlimited to:

10. severe cardiac rhythm or conduction abnormalities, such as ventriculararrhythmias or Ⅲ degree atrioventricular block requiring clinical intervention;

11. prolonged QT interval at rest (QTc > 450 msec in men or QTc > 470 msec inwomen);

12. myocardial infarction, unstable angina, cardiac angioplasty or stentimplantation, coronary artery/peripheral artery bypass grafting, New York HeartAssociation (NYHA) class III or IV congestive heart failure, cerebrovascularaccident, or transient ischemic attack within 6 months before the first dose.

13. Active autoimmune diseases and inflammatory diseases, such as systemic lupuserythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis,inflammatory intestinal diseases and Hashimoto's thyroiditis, etc., excluding type Idiabetes mellitus, hypothyroidism that can be controlled only by replacementtherapy, and skin diseases without systemic treatment (such as vitiligo andpsoriasis).

14. Other malignant tumors that have progressed or require treatment within 3 yearsbefore the first dose, except for radical basal cell carcinoma of the skin, squamouscell carcinoma of the skin, superficial bladder cancer, radical resection ofcarcinoma in situ, such as carcinoma in situ of the breast, prostate cancer; Notes:Patients with localized low-risk prostate cancer (defined as stage ≤T2a, Gleasonscore ≤6, and PSA < 10ng/mL at prostate cancer diagnosis (as measured) who hadreceived radical treatment and no biochemical recurrence of prostate specificantigen (PSA) were eligible to participate in this study).

15. A history of (non-infectious) interstitial lung disease (ILD)/pulmonary inflammationrequiring steroid treatment, or current ILD/ pulmonary inflammation, or suspectedILD/ pulmonary inflammation that cannot be ruled out by imaging at screening.

16. Before starting the study treatment, there are:

17. Poorly controlled diabetes (fasting blood glucose ≥ 13.3 mmol/L)

18. Poorly controlled hypertension (systolic blood pressure ≥ 140 mmHg and/ordiastolic blood pressure ≥ 90 mmHg)

19. History of hypertensive crisis or hypertensive encephalopathy.

20. Unstable deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiringmedical intervention within 6 months before screening; Infusion-related thrombosiswas excluded.

21. Patients with central nervous system (CNS) metastases and/or carcinomatousmeningitis (meningeal metastases). Patients who had received treatment for brainmetastases (radiotherapy or surgery; Patients with stable brain metastases who hadstopped radiotherapy or surgery 28 days before the first dose were eligible.Patients with cancerous meningitis (meningeal metastases) were excluded even if theywere treated and judged to be stable. Stable disease was defined as beingasymptomatic, in stable condition, and not requiring steroid therapy for more than 4weeks before starting study treatment.

22. Patients with pleural effusion, pericardial effusion or ascites with clinicalsymptoms or requiring repeated drainage.

23. Patients with a history of allergy to recombinant humanized antibody or human-mousechimeric antibody or to any excipients of BL-B01D1.

24. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT).

25. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, activehepatitis B virus infection (HBV-DNA copy number > 103 IU/ml) or active hepatitis Cvirus infection (HCV antibody positive and HCV-RNA > detection limit).

26. Active infections requiring systemic therapy, such as severe pneumonia, bacteremia,sepsis, etc.

27. Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of the last dose).

28. Persons with a history of psychotropic drug abuse and inability to quit or mentaldisorders.

29. Other circumstances considered by the investigator to be inappropriate forparticipation in the trial.