Autologous CD30.CAR-T in Combination With Nivolumab in cHL Patients After Failure of Frontline Therapy

Upon successful leukapheresis to produce CD30.CAR-T cells, patients will enter the treatment phase of the study. Treatments will include 4 cycles of nivolumab and CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy). Patients will then enter the post-treatment follow-up phase of the study, whereby patients will undergo either autologous stem cell transplant or continue to receive up to 6 additional treatment cycles of nivolumab. Patients will be followed for response assessments and safety monitoring until end of study (EOS); approximately 3 years after leukapheresis. Long-term follow-up will continue with additional safety monitoring and survival for up to 15 years after Leukapheresis.

Inclusion criteria

• Signed ICF
• Male or female patients who are 12 years of age and above
• Relapsed or refractory CD30+ cHL following failure of a standard frontline chemotherapy
• At least 1 lesion, which must be fluordeoxyglucose positron emission tomography (FDG-PET) avid and measurable by PET-CT scan
• Adequate laboratory parameters including hematologic, renal, hepatic, and coagulation function
• 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)
• Anticipated life expectancy > 12 weeks
• No active infections including COVID 19 at Screening

Exclusion criteria

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