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
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
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:
PLT <75×10⁹/L during prior chemotherapy cycle;
Receiving mono/combination chemotherapy (may include targeted/immunotherapy). 5.Phase Ib: Stratified Requirements:
PLT <50×10⁹/L, or
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;
Females: Negative serum β-HCG within 28 days;
Males: No sperm donation from first dose to 180 days post-last dose.
Exclusion Criteria:
Pregnancy/Lactation: Pregnant or breastfeeding females.
Hypersensitivity: Known allergy to protein-based drugs (e.g., recombinant proteins, mAbs) or excipients of the investigational product.
Active Infection: Acute infection requiring IV antibiotics without clinical control.
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
Anticoagulant Use: Anticoagulants/antiplatelet drugs ≤5 half-lives pre-dose or needed during study (aspirin washout ≥7 days).
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.