A phase II open-label multicenter study to assess the efficacy and safety of AFM13 in patients with relapsed or refractory CD30-positive peripheral T-cell lymphoma or transformed mycosis fungoides: The REDIRECT study design and rationale.

Abstract

TPS3148 Background: AFM13 is a tetravalent, bispecific (anti-CD30/anti-CD16A) recombinant antibody being developed for the treatment of CD30-positive T-cell malignancies and Hodgkin lymphoma. AFM13 selectively kills CD30-positive tumor cells by engaging and activating natural killer cells and macrophages. AFM13 was well tolerated at doses of 0.01 to 7 mg/kg and showed clinical activity in patients with relapsed/refractory (R/R) Hodgkin lymphoma in a Phase 1 study. In an ongoing biomarker Phase 1b/2a study in patients with R/R CD30-positive lymphomas with cutaneous involvement, 4 of 8 patients responded (at different doses) including one CR. Based on these findings, this Phase 2 study (REDIRECT) has been initiated. Methods: This is a Phase 2, open-label, multicenter global study investigating the efficacy and safety of AFM13 in patients with R/R CD30-positive peripheral T cell lymphoma (PTCL) or transformed mycosis fungoides (TMF). AFM13 is administered at 200 mg weekly via an intravenous infusion until disease progression, unacceptable toxicity, investigator discretion or withdrawal of consent. Cohorts A and B include PTCL patients with ≥10%, and ≥1% to <10% CD30 expression by IHC, respectively. Cohort C includes patients with TMF who express ≥1% CD30. Eligible PTCL patients must have received at least 1 prior line of systemic therapy and, if diagnosed with systemic anaplastic large cell lymphoma, must have failed or be intolerant to brentuximab vedotin. Eligible patients with TMF must have received at least 1 prior line of systemic therapy and have exhausted systemic therapies with regular approval for their disease. This global trial started enrollment in Oct 2019. The primary endpoint is objective response rate as confirmed by an Independent Review Committee for all cohorts. The study will also assess investigator-measured efficacy parameters, safety, PK, immunogenicity and QOL. Disease assessment will be done at screening and every 8 weeks for the first 3 assessments, then every 12 weeks thereafter, regardless of any treatment/cycle delays that may occur. ClinicalTrials.gov identifier: NCT04101331.