Overview

This phase II study is designed to investigate the efficacy and safety of BL-B01D1 monotherapy, SI-B003 monotherapy, and BL-B01D1+SI-B003 combination therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (non-nasopharyngeal carcinoma) and other solid tumors.

Eligibility

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:
   1. 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);
   2. Cohort_C Stage II patients who had not received any previous systemic antitumor therapy (other than induction chemotherapy, neoadjuvant, or adjuvant therapy) for recurrent or metastatic HNSCC (non-nasopharyngeal); Treatment failure was defined as disease progression during or after systemic antitumor therapy.

             Intolerance refers to the refusal of patients to continue the original regimen due to
             grade 3-4 adverse reactions after receiving standard treatment.
             Note: Recurrence or disease progression within 6 months after the last chemotherapy of
             multimodal therapy was considered as the first line of treatment.
          6. Consent to provide archival tumor tissue specimens (10-12 unstained sections
             (anti-slip) surgical specimens (thickness 4-5μm)) or fresh tissue samples from primary
             or metastatic lesions within 3 years. If participants cannot provide tumor tissue
             samples, they can be enrolled if they meet other inclusion and exclusion criteria
             after the evaluation of the investigator.
          7. 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 a measurable
             lesion only if there was definite disease progression after radiation therapy.
          8. No blood transfusions and no use of cell growth factors and/or platelet-raising drugs
             during the 14 days prior to the screening period must be allowed, and the organ
             function level must meet the following criteria:
               1. Blood routine: hemoglobin (HGB) ≥ 90g/L; Absolute neutrophil count (NEUT) ≥
                  1.5×10 9 /L; Platelet count (PLT) ≥ 100×10 9 /L;
               2. Renal function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50
                  mL/min (according to Cockcroft and Gault formula).
               3. Liver function: total bilirubin (TBIL≤1.5 ULN), alanine aminotransferase (ALT)
                  and aspartate aminotransferase (AST) were all ≤2.5 ULN, and AST and ALT were both
                  ≤5.0 ULN when liver metastasis was present;
               4. coagulation function: international normalized ratio (INR) ≤1.5 and activated
                  partial thromboplastin time (APTT) ≤1.5ULN;
               5. no severe cardiac dysfunction with left ventricular ejection fraction ≥50%;
               6. proteinuria ≤2+ or ≤1000mg/24h.
          9. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by
             NCI-CTCAE v5.0 (except for asymptomatic laboratory abnormalities such as ALP
             elevation, hyperuricemia, and hyperglycemia, as judged by the investigator, and
             toxicity without safety risk, such as alopecia, grade 2 peripheral neurotoxicity, or
             decreased hemoglobin ≥90g/L, as judged by the investigator).
         10. For premenopausal women with childbearing potential, a pregnancy test must be
             performed within 7 days before the start of treatment, the serum or urine pregnancy
             test must be negative, and the patient must not be lactating; All enrolled patients
             should 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; Oral
             fluorouracil drugs such as S-1, capecitabine, or palliative radiotherapy within 2
             weeks before the first dose.
          3. Non-squamous cell tissue confirmed by histopathology and/or cytology must be excluded.
          4. Cohort_C Stage II patients who had received any previous systemic therapy for
             recurrent or metastatic HNSCC (other than induction chemotherapy, adjuvant or
             neoadjuvant therapy) were excluded.
          5. Cohort_C with a history of immunotherapy and grade ≥3 irAE or grade ≥2 immune-related
             myocarditis, excluded.
          6. Cohort_C cohort_c who had received immunomodulatory drugs (including but not limited
             to thymosin, interleukin-2, interferon, etc.) within 14 days before the first dose of
             study drug was excluded.
          7. Systemic corticosteroids (> 10mg/ day of prednisone, or the equivalent of another
             corticosteroid) are required within 2 weeks before the first dose of the study dose;
             Exceptions were inhaled or topical corticosteroids or physiological replacement doses
             of corticosteroids for adrenal insufficiency.
          8. A history of immunotherapy with grade ≥3 irAE or grade ≥2 immune-related myocarditis
             must be excluded.
          9. A history of severe cardiovascular and cerebrovascular diseases, including but not
             limited to:
               1. severe cardiac rhythm or conduction abnormalities, such as ventricular
                  arrhythmias or Ⅲ degree atrioventricular block requiring clinical intervention;
               2. prolonged QT interval at rest (QTc > 450 msec in men or QTc > 470 msec in women);
               3. myocardial infarction, unstable angina, cardiac angioplasty or stent
                  implantation, coronary artery/peripheral artery bypass grafting, New York Heart
                  Association (NYHA) class III or IV congestive heart failure, cerebrovascular
                  accident, or transient ischemic attack within 6 months before the first dose.
         10. Active autoimmune diseases and inflammatory diseases, such as systemic lupus
             erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis,
             inflammatory intestinal diseases and Hashimoto's thyroiditis, etc., excluding type I
             diabetes mellitus, hypothyroidism that can be controlled only by replacement therapy,
             and skin diseases without systemic treatment (such as vitiligo and psoriasis).
         11. Other malignant tumors that have progressed or require treatment within 3 years before
             the first dose, except for radical basal cell carcinoma of the skin, squamous cell
             carcinoma of the skin, superficial bladder cancer, radical resection of carcinoma in
             situ, such as carcinoma in situ of the breast, prostate cancer; Notes: Patients with
             localized low-risk prostate cancer (defined as stage ≤T2a, Gleason score ≤6, and PSA <
             10ng/mL at prostate cancer diagnosis (as measured) who had received radical treatment
             and no biochemical recurrence of prostate specific antigen (PSA) were eligible to
             participate in this study).
         12. A history of (non-infectious) interstitial lung disease (ILD)/pulmonary inflammation
             requiring steroid treatment, or current ILD/ pulmonary inflammation, or suspected ILD/
             pulmonary inflammation that cannot be ruled out by imaging at screening.
         13. Before starting the study treatment, there are:
               1. Poorly controlled diabetes (fasting blood glucose ≥ 13.3 mmol/L)
               2. Poorly controlled hypertension (systolic blood pressure ≥ 140 mmHg and/or
                  diastolic blood pressure ≥ 90 mmHg)
               3. History of hypertensive crisis or hypertensive encephalopathy.
         14. Unstable deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring
             medical intervention within 6 months before screening; Infusion-related thrombosis was
             excluded.
         15. Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis
             (meningeal metastases). Patients who had received treatment for brain metastases
             (radiotherapy or surgery; Patients with stable brain metastases who had stopped
             radiotherapy or surgery 28 days before the first dose were eligible. Patients with
             cancerous meningitis (meningeal metastases) were excluded even if they were treated
             and judged to be stable. Stable disease was defined as being asymptomatic, in stable
             condition, and not requiring steroid therapy for more than 4 weeks before starting
             study treatment.
         16. Patients with pleural effusion, pericardial effusion or ascites with clinical symptoms
             or requiring repeated drainage.
         17. Patients with a history of allergy to recombinant humanized antibody or human-mouse
             chimeric antibody or to any excipients of BL-B01D1.
         18. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation
             (Allo-HSCT).
         19. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active
             hepatitis B virus infection (HBV-DNA copy number > 103 IU/ml) or active hepatitis C
             virus infection (HCV antibody positive and HCV-RNA > detection limit).
         20. Active infections requiring systemic therapy, such as severe pneumonia, bacteremia,
             sepsis, etc.
         21. Had participated in another clinical trial within 4 weeks before the first dose
             (calculated from the time of the last dose).
         22. Persons with a history of psychotropic drug abuse and inability to quit or mental
             disorders.
         23. Other circumstances considered by the investigator to be inappropriate for
             participation in the trial.