FDA grants orphan drug designation to AFM13 and fast track designation to tipifarnib for T-cell lymphomas

The United States Food & Drug Administration (FDA) has granted orphan drug designation to AFM13, a CD30- and CD16A-binding innate cell engager, for the treatment of T-cell lymphoma, including peripheral T-cell lymphoma (pTCL).¹ The FDA has also granted fast track designation to tipifarnib for adult patients with relapsed/refractory (R/R) T-cell lymphomas, including angioimmunoblastic T-cell lymphoma (AITL), follicular T-cell lymphoma (FTCL), and nodal pTCL with a T follicular helper (TFH) phenotype.²

AFM13¹

• AFM13 is a first-in-class tetravalent, bispecific innate cell engager that binds to
  • CD30 on tumor cells
  • CD16A on natural killer cells
• It is being investigated in patients with pTCL and other CD30-positive lymphomas
• An ongoing phase II study, REDIRECT (NCT04101331), is investigating AFM13 as monotherapy in patients with R/R CD30-positive pTCL
• AFM13 has previously been granted orphan drug designation by the FDA for Hodgkin lymphoma

Tipifarnib³

• Tipifarnib is a selective inhibitor of farnesyltransferase
• Results from a phase II trial (NCT02464228) of tipifarnib in R/R T-cell lymphomas were presented at the 61st meeting of the American Society of Hematology (ASH) in December 2019
  • Single-arm, multicenter, open-label trial of 50 patients with AITL and CXCL12⁺ pTCL
  • Designed in two stages (11 + 7 patients) to assess efficacy, safety, and biomarkers of tipifarnib in patients with R/R pTCL
    • Based on initial findings, the study was amended to include a cohort of patients with AITL (n = 12) and pTCL with CXCL12 rs2839695 A/A genotype (wild type [wt] CXCL12 3’UTR, n = 12)
  • All patients received tipifarnib, orally, twice daily on Days 1–21 of 28-day treatment cycles until disease progression or unacceptable toxicity
  • Primary endpoint: overall response rate (ORR)
  • At a cut-off of May 24, 2019, 50 patients with pTCL had been treated: 19 in Stages 1 and 2, and 31 in the AIRL and wt CXCL12 3’UTR cohort
  • In Stages 1 and 2, 18 patients were evaluable for response:
    • Partial response (PR): 3
    • Stable disease (SD): 5
  • In the AITL cohort, 11 patients were evaluable for response:
    • ORR: 45%
    • Clinical benefit rate (CBR): 73%
      • Complete response: 3
      • PR: 2
      • SD: 3
  • In the wt CXCL12 3’UTR cohort, 12 patients were evaluable for response:
    • ORR: 42%
      • CR: 3
      • PR: 2
  • For safety (n = 48), treatment-emergent adverse events (TEAEs) were observed in all evaluable patients. Drug-related Grade > 3 TEAEs occurring in > 10% of patients were
    • Neutropenia: 40%
    • Thrombocytopenia: 33%
    • Leukopenia: 25%
    • Anemia: 19%
    • Febrile neutropenia: 19%
  • There were 14 deaths on study, with one deemed to be related to treatment (lung infection)
• A future trial will enroll approximately 128 patients with AITL (or similar) who have relapsed or are refractory to ≥ 1 prior systemic regimen²