INVESTIGATING SAFETY AND PRELIMINARY EFFICACY OF AFM13 PLUS PEMBROLIZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY HODGKIN LYMPHOMA AFTER BRENTUXIMAB VEDOTIN FAILURE

Abstract

Background: AFM13 is a bispecific, tetravalent NK cell-engaging antibody construct binding to CD30 on Hodgkin Lymphoma (HL) cells and CD16A on NK cells1. Pembrolizumab is a PD-1 blocking antibody that induces high response rates in patients (pts) with relapsed or refractory HL (RRHL)2. AFM13 has shown clinical activity in pts with RRHL in a Phase 1 study3. Preclinical data of the combination of AFM13 with PD-1 inhibition suggest synergism4. Method(s): This Phase 1b dose escalation/extension study is evaluating the safety, tolerability and preliminary efficacy of the combination of AFM13 with pembrolizumab as salvage therapy after failure of standard therapies including brentuximab vedotin (BV) in pts with HL (NCT02665650). Pts receive escalating doses of AFM13 in combination with pembrolizumab following the classical 3+3 design. Response assessment is performed every 12 weeks by PET/CT according to the Lugano Classification5. Data as of February 12, 2019 are presented. Result(s): All thirty pts have been enrolled. The median age is 34 years (18-73), with a median of 4 (3-7) prior lines of therapy. All pts have failed standard treatments including BV and 43% had BV as their latest therapy. Thirty seven percent have undergone prior autologous stem cell transplantation. Twelve pts were enrolled into the dose escalation cohorts and 18 into the Extension Cohort. All 30 pts completed the dose limiting toxicity (DLT) observation period. No DLTs occurred in Cohorts 1/2, one DLT occurred in Cohort 3 (missed >=25% of AFM13 during the DLT period) and one DLT occurred in the Extension Cohort (Grade (G)4 infusion-related reaction (IRR)). Adverse Events were mainly G1/G2 and included IRRs (87%), rash (30%), nausea (23%), pyrexia (23%), and diarrhea (20%). G3/4 AEs included IRRs (13%), elevated aspartate aminotransferase (3%), gastritis (3%), hypotension (3%), nausea (3%), neutropenia (3%), and vomiting (3%). Included in the efficacy analysis were the best response from all 30 patients. The best overall response rate (ORR) and complete response (CR) rate for pts treated at the dose and schedule chosen for expansion (n=24; Cohort 3 and Extension Cohort) were 88% and 46% by independent assessment. Investigator assessment resulted in an ORR of 88% and CR rate of 42% for these pts. Estimated 6-month PFS rate at the highest treated dose level was 77%. Longer term follow up results will be presented at the meeting. Conclusion(s): The combination of AFM13 and pembrolizumab is welltolerated with most AEs mild to moderate in nature. The ORR of 88% compares favorably to the historical data of pembrolizumab in a similar RRHL population, with the CR rates of 42% and 46% by local and independent assessment, respectively, approximately doubling that of pembrolizumab (CR rates 22-25%)2.