AFM13 in patients with relapsed or refractory classical Hodgkin lymphoma: final results of an open-label, randomized, multicenter phase II trial

Abstract

In patients with relapse of classical Hodgkin lymphoma (cHL) after autologous stem cell transplant, brentuximab vedotin and anti-PD1 treatment, the outcome is poor. To assess the efficacy of the bispecific anti-CD30/CD16A, NK-cell engaging antibody AFM13 and to select the optimal treatment schedule (arm A–C), we initiated a randomized two-stage phase II trial (NCT02321592). Due to slow recruitment, the trial was terminated after treatment of 25 patients. Treatment with AFM13 was well tolerated: only two treatment-associated serious adverse events (SAEs) were reported; all SAEs resolved completely. With an objective response rate (ORR) of 16.7% (1/5 in arm A, 1/11 in arm B, and 2/8 in arm C) and a 12-month progression-free survival (PFS) of 12.6% (95% CI 3.2–28.9), treatment efficacy of AFM13 monotherapy in all evaluable patients was modest. The continuous application schedule (arm C) might be more effective, but the visit schedule should be better aligned with patients’ daily life.

Keywords:

• Relapsed classical Hodgkin lymphoma
• bispecific anti-CD30/CD16A-antibody
• AFM13
• NK-cell mediated immune-response
• phase II trial
• immunotherapy

Acknowledgements

The authors would like to thank the patients and their families as well as all trial centers for participation in this clinical trial.

Author contributions

Conception of the trial design and administrative support: S.S., P.A., F.M., E.A., B.P., B.P.J., K.C., D.M. Providing study material or patients: H.A. B.N., K.C., M.S., B.M., G-T.C., T.S., De W.M., v.T.B., M.J., B.P.J. Central assessment of PET/CT: K.C. and D.M. Statistical analysis: P.A. Preparation of draft and revision of manuscript: S.S., P.A., F.M., and M.J. All authors approved of the submitted and final version.

Disclosure statement

P.J. Bröckelmann: research grants from BeiGene, Bristol Myers Squibb, Merck Sharpe & Dohme, and Takeda; and personal fees and non-financial support from Bristol-Myers Squibb, Celgene, and Takeda; all outside the submitted work. A. Engert: consultant or advisory role: Takeda, ADC Therapeutics, Tessa Therapeutics, and AstraZeneca; honoraria: Takeda, BMS, Novartis, MSD, Hexal, and AstraZeneca; research funding: Takeda, BMS, Affimed, and all outside the submitted work. C. Grosse-Thie: travel grants of BMS, Abbvie, personal fees for presentations from MSD, BMS, Novartis, Abbvie, and all outside the submitted work. J. Momotow, A. Plütschow, N. Basara, A. Huettmann, C. Koenecke, S. Martin, M. Bentz, S. Thorspecken, M. de Wit, C. Kobe, M. Dietlein, and M. Fuchs: no disclosures. S. Sasse: travel grants of GSK, Takeda; outside the submitted work. B. v. Tresckow: research funding from Novartis, MSD, and Takeda; consulting fees from BMS/Celgene, Incyte, Miltenyi, Novartis, Pentixafarm, Amgen, Pfizer, Takeda, MSD, and Gilead; honoraria for lectures and presentations by AstraZeneca, Novartis, Roche Pharma AG, Takeda, and MSD. Travel support by AbbVie, AstraZeneca, Kite-Gilead, MSD, Takeda, and Novartis. All outside the submitted work. P. Borchmann: Novartis: Honoraria, Research Funding, outside the submitted work.