CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Signed ICF
2. Male or female patients who are 12 years of age and above
3. Relapsed or refractory CD30+ cHL following failure of a standard frontline chemotherapy
4. At least 1 lesion, which must be fluordeoxyglucose positron emission tomography (FDG-PET) avid and measurable by PET-CT scan
5. Adequate laboratory parameters including hematologic, renal, hepatic, and coagulation function
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, or equivalent either Karnofsky performance status (for patients ≥ 16 years of age) or Lansky performance status (for patients \< 16 years of age)
7. Anticipated life expectancy \> 12 weeks
8. No active infections including COVID 19 at Screening

Exclusion Criteria:

1. Evidence of lymphomatous involvement of the central nervous system (CNS)
2. Presence of clinically relevant or active seizure disorder, stroke, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
3. Symptomatic cardiovascular disease: Class III or IV according to the New York Heart Association (NYHA) Functional Classification
4. Active uncontrolled bleeding or a known bleeding diathesis
5. Inadequate pulmonary function defined as oxygen saturation by pulse oximetry \< 90% on room air
6. Echocardiogram (ECHO) or Multi-gated Acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) \< 45%
7. Prior receipt of salvage therapy, for relapsed or refractory cHL, including allogeneic or ASCT
8. Prior receipt of investigational CD30.CAR-T cells
9. Receiving any investigational agents or any tumor vaccines
10. Receiving any live/attenuated vaccines
11. Ongoing treatment with immunosuppressive drugs or chronic systemic corticosteroids
12. Unresolved \> Grade 1 non-hematologic toxicity associated with any prior treatments
13. Previous history of known or suspected autoimmune disease within the past 5 years
14. Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
15. Evidence of human immunodeficiency virus (HIV) infection
16. Evidence of active viral infection with hepatitis B virus (HBV)
17. Evidence of active viral infection with hepatitis C virus (HCV)
18. Active second malignancy or history of another malignancy within the last 3 years
19. History of hypersensitivity reactions to murine protein-containing products or other product excipients
20. Any allergic or adverse reaction to nivolumab, fludarabine, or bendamustine that precludes treatment with these agents
21. History of a significant irAE from prior immune checkpoint inhibitor therapy

主要终点：Safety of autologous CD30.CAR-T in combination with nivolumab · DLT · From first dose of nivolumab (Cycle 1) to end of nivolumab Cycle 4 (each cycle is 28 days)
次要终点：Anti-tumor activity using CR rate of autologous CD30.CAR-T in combination with nivolumab；Overall response rate；Duration of response；Progression-free survival

• Nivolumab and CD30.CAR-T · EXPERIMENTAL · Study treatment will include 4 cycles of nivolumab and a single CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy of Fludarabine and Bendamustine).

This is a Phase 1b, multicenter, open-label, single arm study to evaluate the safety and efficacy of the combination therapy, CD30.CAR-T and the programmed cell death protein-1 (PD-1) checkpoint inhibitor, nivolumab, in patients aged 12 years of age and above with relapsed or refractory classical Hodgkin lymphoma (cHL) following failure of standard frontline therapy.