Safety and Preliminary Efficacy of F0002, an Anti-CD30 Antibody-Drug Conjugate, in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma Previously Treated with Anti-PD-1 or PD-L1 Therapy: Results from F0002-101 Phase 1 Study

Background:

F0002 is an antibody drug conjugate comprising an anti-CD30 antibody linked to the potent cytotoxin DM1 via a non-cleavable maleimidomethyl cyclohexane-1-carboxylate (MCC) thioether linker. Previous non-clinical studies demonstrated its potential antitumor efficacy. Here we first reported the results of the phase I study in patients with Relapsed or Refractory (R/R) classical Hodgkin Lymphoma (cHL) (NCT03894150).

Methods:

Eligible patients aged ≥18 years with measurable, histologically confirmed R/R cHL or other lymphoma were enrolled from four study sites in China. R/R cHL was defined as cHL patients with failed autologous stem cell transplant (ASCT) treatment or failure of at least 2 lines of prior systemic chemotherapy.

This study consisted of two parts: dose-escalation and dose-expansion. In dose-escalation part (Part 1), F0002 was administered every 3 weeks at doses ranging from 0.3mg/kg to 3.6mg/kg until disease progression or unacceptable toxicity. Part 2 was dose expansion with two dose groups (2.4mg/kg and 3.0mg/kg Q3W) in R/R cHL patients. The primary endpoint was safety and maximum tolerated dose (MTD) while secondary endpoints included efficacy, pharmacokinetics, and immunogenicity.

Results

From April 2019 to April 2024, a total of 45 patients were enrolled and received at least one treatment with F0002 (13 in part 1; 32 in part 2). 64.4% of enrolled patients were male, with a mean age was 35.62±10.18 (range: 21, 69), and 84.4% had stage III/IV disease. Most patients (95.6%) had cHL, with 2 patients having NK/T lymphoma and peripheral T lymphoma who were at 2.4mg/kg dose level. Enrolled patients had a median of 5 prior lines (range: 2, 13) of systemic therapies, 86.7% had previously received PD-1/PD-L1 immunotherapy (92% in 3.0mg/kg group). No deaths were reported in the study. Of the 43 patients available for tumor assessment, the overall response rate (ORR) was 30.2% (13/43), disease control rate (DCR) was 74.4%, median duration of response (mDOR) was 5.13 months, median progression-free survival (mPFS) was 5.55 months. Two patients achieved complete response (CR) (both in 3.0mg/kg), 11 patients achieved partial response (PR), and 19 patients achieved stable disease (SD). In 3.0mg/kg group, ORR was 40%, DCR was 80%, mDOR was 7.23 months, mPFS was 5.85 months. Notably, one patient achieved CR with a DOR of 12.45 months and PFS of 13.80 months while another patient achieved CR with a DOR of 14.95 months and PFS of 16.10 months.

Treatment-emergent adverse events (TEAEs) occurred in all patients (100%). Treatment-related adverse events (TRAEs) were reported in 97.8% of patients. The most common TRAEs (≥20%) included thrombocytopenia (84.4%), AST increased (71.1%), ALT increased (64.4%), anemia and GGT increased (33%), neutrophil count decreased and fever (31.1%), WBC count decreased and blood bilirubin increased (26.7%), and BIL increased and ALP increased (24.4%). Grade 3/4 TRAEs with an incidence of ≥5% were thrombocytopenia (51.1%), GGT increased (13.3%), ALT increased (8.9%), 8.9% anemia (8.9%) and 6.7%WBC count decreased (6.7%). In the 3.6mg/kg group, 2 patients experienced dose-limiting toxicities (DLTs) (both grade 4 thrombocytopenia), leading to treatment discontinuation.

Conclusions

F0002 demonstrated a tolerable safety profile and potential efficacy in patients with classical Hodgkin lymphoma, with an ORR of 40% and DCR of 80% in the 3.0mg/kg dose group. Additionally, F0002 showed potential efficacy in patients previously treated with PD-1/PD-L1 inhibitors. Further exploration of the 3.0 mg/kg dose is warranted to clarify the anti-tumor efficacy of F0002 in PD-1/PD-L1 treated patients.

Yan:Shanghai Fudan-Zhangjiang Bio-pharmaceutical Co., Ltd: Current Employment. Zhou:Shanghai Fudan-Zhangjiang Bio-pharmaceutical Co., Ltd.,: Current Employment. Sun:Shanghai Fudan-Zhangjiang Bio-pharmaceutical Co., Ltd: Current Employment. Liu:Shanghai Fudan-Zhangjiang Bio-pharmaceutical Co., Ltd: Current Employment.