AFM13 is currently also being evaluated on its own in lymphoma in a phase 2 registrational study.
Affimed’s innate cell engager therapy, AFM13, has demonstrated promising efficacy in patients with CD30-positive, relapsed/refractory (R/R) lymphoma when precomplexed with cord blood (CB)-derived natural killer (NK) cells.1
Positive data from a phase 1 trial (NCT04074746) being conducted at MD Anderson Cancer Center were presented at the American Association for Cancer Research (AACR) Annual Meeting, April 8-13, 2022, in New Orleans, Louisiana, by first author Yago Nieto, MD, PhD, professor, department of stem cell transplantation, division of internal medicine, The University of Texas MD Anderson Cancer Center.
“The data that we report today are highly encouraging. All patients on this trial were refractory to all available treatment options. Still the combination of AFM13 and precomplexed NK cells resulted in a 100% response rate and a 62% rate of complete responses. We are excited to see a deepening of responses from partial responses to complete responses with a second cycle and have amended the study to allow patients to receive additional cycles, which may further increase the efficacy,” Andreas Harstrick, MD, chief medical officer, Affimed, said in a statement.2 “To our knowledge, this is the highest response rate reported so far in Hodgkin Lymphoma patients with treatment-refractory disease.”
AFM13 is a first-in-class CD30/CD16a bispecific antibody construct. In this small, academic, phase 1 trial, the therapy was combined with IL-2/IL-15/IL-18 preactivated and expanded CB-derived NK cells prior to infusion.1 This combination demonstrated greater activity than AFM13 alone.
Nineteen patients have been treated in the study to date; these patients had a median age of 37 years (range, 20-68), were mostly male (n = 13), had a median of 6 prior lines of therapy (range, 1-14), and a median of 5 (range, 1-14) prior relapses or progressions of disease. Study participants received 2 cycles of fludarabine/cyclophosphamide prior to AFM13-CB NK cell infusion followed by weekly infusions of AFM13. CB NK cells expanded as early as 3 days after infusion and persisted for up to 1 month.
Patients have been treated in 3 dose levels, 106 NK cells/kg (n = 3), 107 NK cells/kg (n = 3), and 108 NK cells/kg (n = 13). All patients had active, progressive disease at enrollment and no patients received bridging therapy. Cords were not selected according to human leukocyte antigen match, which was 0/6 (n = 16), 1/6 (n = 17), 2/6 (n = 2), 3/6 (n = 1), and 4/6 (n = 1).
Investigators reported 17 responses to therapy, including 8 complete responses (CR) and 9 partial responses (PR). There were 2 cases of progressive disease. All patients treated at the third dose level, which is the recommended phase 2 dose, responded with 6 CRs and 7 PRs. Two patients received an autologous stem cell transplant after treatment. Progression-free survival was 58% at a median follow-up of 6 months (range, 2-16) and overall survival was 79%.
The therapy was well-tolerated, with no cases of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft –versushost disease. There were 6 infusion-related reactions, 1 of which was grade 3 and 5 of which were grade 2, in 110 infusions of AFM13 alone with no reactions to the complexed AFM13-NK cell infusion.
“A year ago, we were struck with hopeful optimism when the first four patients in the study all showed a response. Now, we are again presenting data at AACR and the results not only hold strong in a larger patient population but also show an increasing number of CRs with early but encouraging durability,” Adi Hoess, MD, PhD, chief executive officer, Affimed, added to the statement.2 “These ongoing successes with AFM13 represent an important milestone for Affimed and could mark a turning point in the innate immuno-oncology space, potentially setting the stage for expanding this approach to additional cancer indications. Our goal is to leverage the distinct features of our ROCK platform to generate best-in-class ICE molecules that drive effective innate immune cell activation for the benefit of broad patient populations, addressing hematologic and solid tumor malignancies.”
Affimed is currently conducting the phase 2 REDIRECT registrational study (NCT04101331) of AFM13 alone in R/R CD30-positive T-cell lymphoma or transformed mycosis fungoides, which completed enrollment in 2021. Topline data from the trial is expected to be read out in the second half of 2022.
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