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

Phase 1b Study Evaluating the Safety and Efficacy of Autologous CD30.CAR-T in Combination With PD-1 Checkpoint Inhibitor (Nivolumab) in Relapsed or Refractory Classical Hodgkin Lymphoma Patients After Failure of Frontline Therapy (ACTION)

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.

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:

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