A Phase I Clinical Study to Evaluate the Safety, Tolerability, Immunogenicity, Preliminary Efficacy and Pharmacokinetics of SCB-219M in the patients with chemotherapy-induced thrombocytopenia (CIT)

The purpose of this trial is to evaluate the safety, tolerability, immunogenicity, and PK characteristics of single and multiple subcutaneous injections of SCB-219M for CIT, explore the MTD and BED, and preliminarily observe and evaluate efficacy. The trial is divided into a dose escalation phase (Ia) and an expansion phase (Ib).

Inclusion Criteria:

1. Age: 18-75 years (inclusive), voluntary participation with signed informed consent and commitment to protocol-defined visits.
2. Body Weight: ≥40 kg.
3. Diagnosis: Histopathologically/cytopathologically confirmed malignant solid tumors or lymphoma.
4. Phase Ia: Platelet (PLT) & Treatment Status:

1. PLT <75×10⁹/L during prior chemotherapy cycle;

2. Receiving mono/combination chemotherapy (may include targeted/immunotherapy). 5.Phase Ib: Stratified Requirements:

   • Group A (1st-line CIT prophylaxis/therapy):

1. PLT <50×10⁹/L, or

2. PLT 50-75×10⁹/L. • Group B (2nd-line CIT therapy/refractory cases): Second-line CIT treatment for refractory or treated CIT patients who failed first-line therapy (rhTPO/IL-11) with platelet count <50×10⁹/L 6.Refractory/Treated CIT Definition:

   • Platelet count remains <50×10⁹/L or increases by <20×10⁹/L within 14 days after completing first-line CIT therapy (e.g., rhTPO or rhIL-11), with baseline PLT <50×10⁹/L at enrollment.

     7.Toxicity Resolution: Prior anti-tumor toxicity ≤ Grade 2 (CTCAE v5.0) at enrollment (alopecia/vitiligo/subjective symptoms excluded).

     8.ECOG PS: 0-2. 9.Life Expectancy: ≥3 months (investigator-assessed). 10.Baseline Laboratory (Pre-dose):

   • a) Creatinine ≤1.5×ULN; CrCl >40 mL/min;

   • b) PT/APTT/INR 80-120% of normal range;

   • c) ANC ≥1.5×10⁹/L;

   • d) Hemoglobin ≥70 g/L;

   • e) Albumin ≥25 g/L. 11.Liver Function:

   • a) ALT/AST ≤3×ULN (≤5×ULN if liver metastasis);

   • b) Total bilirubin ≤2.0×ULN (Gilbert's syndrome/asymptomatic cholelithiasis exempted).

     12.Contraception:

   • Fertile subjects must use ≥1 method:

     o Absolute abstinence;

     • Double-barrier (condom + spermicidal diaphragm);
     • IUD/hormonal contraceptives (oral/implant/patch/injection);
     • Hysterectomy/bilateral salpingectomy/tubal ligation (females or partners);
     • Vasectomy/azoospermia (males or partners).

   • Females: Negative serum β-HCG within 28 days;

   • Males: No sperm donation from first dose to 180 days post-last dose.

Exclusion Criteria:

1. Pregnancy/Lactation: Pregnant or breastfeeding females.

2. Hypersensitivity: Known allergy to protein-based drugs (e.g., recombinant proteins, mAbs) or excipients of the investigational product.

3. Active Infection: Acute infection requiring IV antibiotics without clinical control.

4. Prior Thrombopoietic Agents:

   • Group A: Use within specified windows pre-SCB-219M:

   o Trilaciclib: ≤3 weeks

   o Romiplostim: ≤2 weeks

   o TPO-RAs (e.g., eltrombopag), rhTPO, IL-11, or platelet transfusion: ≤10 days

   • Group B: Use within:

   o Romiplostim/rhTPO/IL-11: ≤7 days

   o TPO-RAs/platelet transfusion: ≤3 days

5. Anticoagulant Use: Anticoagulants/antiplatelet drugs ≤5 half-lives pre-dose or needed during study (aspirin washout ≥7 days).

6. Non-Chemotherapy Thrombocytopenia (within 6 months/unresolved):

1) Clinically significant non-chemotherapy-induced thrombocytopenia (e.g., EDTA-dependent pseudothrombocytopenia) 2) Hematologic malignancies (excluding lymphoma; e.g., leukemia) 3) Multiple myeloma 7.Bleeding Events (within 2 weeks pre-screening):

• Group A: ≥Grade 2 (WHO Bleeding Scale)

• Group B: ≥Grade 3 (WHO Bleeding Scale) 8.Non-CIT Thrombocytopenia Etiologies: 1) Primary immune thrombocytopenia (pITP) 2) Bone marrow failure (e.g., aplastic anemia, Fanconi anemia) 3) Myeloproliferative disorders/MDS 4) Hypersplenism secondary to hematologic/autoimmune diseases 9.Splenectomy/Splenic Effects: Splenic metastasis affecting hematopoiesis; splenectomy/splenic artery embolization ≤12 weeks pre-enrollment.

  10.Uncontrolled Cardiovascular Disease:

• NYHA Class III/IV heart failure

• Pro-thrombotic conditions (e.g., atrial fibrillation, unstable angina)

• QTc >470 ms (>480 ms with bundle branch block)

• Myocardial infarction ≤6 months (Note: Pacemaker/ICD users with normal function eligible) 11.Thrombotic/Coagulation Disorders:

• Coagulopathies

• Arterial/venous thrombosis ≤3 months (excluding PICC-related thrombosis)

• Transient ischemic attack ≤3 months 12.Major Procedures/Radiotherapy: Major surgery/radiotherapy ≤4 weeks pre-dose (except toxicity ≤Grade 2 [CTCAE v5.0], alopecia/vitiligo permitted).

  13.CNS Metastases: Active/untreated CNS or leptomeningeal metastases (asymptomatic brain metastases allowed).

  14.Uncontrolled Hypertension: Resting SBP ≥160 mmHg and/or DBP ≥100 mmHg (two measurements, 2h apart).

  15.Active Infections:

• HIV seropositivity

• Active HBV (HBsAg+ andHBV DNA >LLOQ)

• Active HCV (anti-HCV+ andHCV RNA >LLOQ) 16.Live Vaccines: Live attenuated vaccines ≤4 weeks pre-dose (COVID-19 vaccines permitted except Ad5-vectored type [requires investigator assessment]).

  17.Concurrent Clinical Trials: Participation in other drug/device trials ≤4 weeks pre-dose or planned during study.

  18.Investigator's Discretion: Poor compliance or other factors deemed unsuitable for the study.