CD30/CD16A Tetravalent Bispecific Antibody AFM13 in Combination with Keytruda Doubles Complete Response Rate in Relapsed/Refractory Hodgkin Lymphoma

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Affimed is a clinical-stage immuno-oncology company dedicated to developing innovative therapies that combat cancer by restoring patients’ innate immune capabilities. Recently, the company announced that the results of its Phase Ib clinical study evaluating AFM13 in combination with Merck’s anti-PD-1 therapy Keytruda (pembrolizumab) for the treatment of relapsed or refractory Hodgkin lymphoma (R/R HL) have been published in the journal Blood. The data demonstrated that the combination of AFM13 and Keytruda achieved a higher objective response rate (ORR) compared to Keytruda monotherapy, notably doubling the complete response (CR) rate.

AFM13 is a first-in-class innate cell engager (ICE), a bispecific tetravalent antibody that targets CD30 and CD16. It specifically binds to CD30 on tumor cells and CD16A on innate immune cells, such as natural killer (NK) cells and macrophages. By binding to and activating NK cells and macrophages, AFM13 induces specific and selective killing of CD30-positive tumor cells, thereby harnessing the power of the innate immune system to combat cancer.

AFM13 is the most advanced ICE® clinical program from Affimed’s ROCK platform, currently being developed for the treatment of CD30-positive lymphomas.

This publication presents a dose-escalation study designed to evaluate the safety and preliminary efficacy of AFM13 in combination with Keytruda in patients with relapsed/refractory Hodgkin lymphoma (R/R HL) who were heavily pretreated. The study enrolled 30 patients with R/R HL who were anti-PD-1 naive and had experienced treatment failure after receiving at least two prior therapies, including brentuximab vedotin (BV).

Results showed: (1) Independent review assessment: at the highest dose, the ORR was 88% and the CR was 42% for AFM13 + Keytruda treatment; (2) Investigator review assessment: at the highest dose, the ORR was 88% and the CR was 46% for AFM13 + Keytruda treatment. (3) Subgroup analysis revealed that the highest response rates were observed in the subgroup of patients with primary refractory disease to BV (ORR 85%, CR 46%), with 11 out of 13 patients achieving an objective response.

These data demonstrate superiority over the historical efficacy data of Keytruda monotherapy in a similar patient population: in the KEYNOTE-087 study, the ORR and CR for Keytruda monotherapy were 69% and 22.4%, respectively.

In this study, the combination of AFM13 and Keytruda was well tolerated, with a safety profile consistent with the known safety profiles of each drug. Most adverse events were low-grade and manageable with standard care.

AFM13 proposes a novel approach to activate innate immunity by leveraging the CD16A-directed tumor cell-killing capacity of NK cells and macrophages. Phase 1b studies support the notion that immune checkpoint inhibitors release the brakes on adaptive immune responses, and AFM13 can complement PD-1 checkpoint inhibitors. Through combination therapy, both branches of the immune system—the innate and adaptive immune systems—can be simultaneously triggered to combat tumors.

Dr. Andreas Harstick, Chief Medical Officer of Affimed, stated, “We have demonstrated for the first time that the combination of ICE® and PD-1 checkpoint inhibitors can be administered safely with manageable side effects. The highly encouraging efficacy data, including high response rates and complete response rates, observed in the proof-of-concept study of AFM13 in combination with Keytruda, indicate that activation of innate immunity can enhance the efficacy of existing therapies.”

Reference Source: Affimed Announces Publication of Final Study Results of its Innate Cell Engager Candidate AFM13 in Combination with MSD's anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in Blood

Original Title: Complete Response Rate Doubles! CD30/CD16A Bispecific Tetravalent Antibody Combined with Keytruda Outperforms Monotherapy in Hodgkin Lymphoma