Affimed N.V. (Nasdaq: AFMD) has provided a data update from the ongoing study of the company’s lead innate cell engager (ICE) AFM13 precomplexed with cord blood-derived natural killer (cbNK) cells.
AFM13 is currently being investigated at The University of Texas MD Anderson Cancer Center in a phase 1/2 study in patients with CD30-positive relapsed or refractory Hodgkin and non-Hodgkin lymphomas. The investigator-sponsored study is led by Yago Nieto, M.D., Ph.D., professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson. The study shows a 100% objective response rate (ORR) and an improvement of complete response (CR) rate to 62% at the recommended phase 2 dose (RP2D) in 13 patients after 2 cycles of therapy. The results will be presented during the Clinical Plenary Session on cellular immunotherapies at the American Association for Cancer Research (AACR) Annual Meeting 2022 and will also be covered during an AACR press conference this morning, the company said.
“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,” said Dr Andreas Harstrick, Chief Medical Officer at Affimed. “To our knowledge, this is the highest response rate reported so far in Hodgkin Lymphoma patients with treatment refractory disease.”
As of the cut-off date, the study had enrolled 22 patients with relapsed or refractory CD30+ Hodgkin and non-Hodgkin lymphoma having received a median of seven prior lines of therapy, of whom 19 were evaluable for response. Thirteen response-evaluable patients were treated at the RP2D, including 12 patients with Hodgkin Lymphoma and one patient with non-Hodgkin Lymphoma. Each treatment cycle consists of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed two days later by a single infusion of cytokine-preactivated and expanded cord blood-derived NK cells that are pre-complexed with AFM13. Three weekly infusions of AFM13 (200 mg) monotherapy are subsequently administered and responses are assessed by the investigator on day 28 by FDG-PET, the company said.
The company further explained that all 13 patients treated at the recommended phase 2 dose (108 NK/Kg) achieved a response by Lyric criteria. Of these 13 patients, 8 patients (62%) demonstrated a CR after two cycles of treatment, which represents an increase from 5 patients (38%) demonstrating CR after one cycle of treatment previously announced in December 2021. For the 13 patients treated at the RP2D, median duration of response has not yet been reached. As of the cutoff date, assessment of durability shows:
- Seven patients remain in CR at median follow-up of 6.5 months, including two patients who remain in response after 10 months and two patients who received stem cell transplant and remain in response at 6.5 months
- One patient with a CR experienced disease progression after 7.9 months
- Of the five patients with a PR, one remains in response at 6.3 months and four patients progressed between 2.9 and 4.3 months after initial infusion
Also, the treatment was well tolerated, with minimal side effects beyond the expected myelosuppression from the preceding lymphodepleting chemotherapy. No instances of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft versus host disease were observed. There were six infusion-related reactions in 110 infusions (5.4%) of AFM13 alone and no reactions to the cord blood-derived NK cells precomplexed with AFM13.
“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,” commented Dr. Adi Hoess, Chief Executive Officer at Affimed. “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.”
The trial was originally designed to include up to two cycles. To assess durability beyond two cycles, an amendment has been approved by the U.S. Food and Drug Administration to increase the length of treatment from two up to four cycles, enabling longer follow up of patients, the company noted.
AFM13, a bispecific tetravalent ICE molecule, is designed for high affinity binding, both to CD16A on NK cells and macrophages, and to CD30 on lymphoma cells. AFM13 is also being investigated as a monotherapy and can bind the patient’s own NK cells, thus boosting their existing capacity to fight cancerous cells. When precomplexed with AFM13, NK cells exhibit immediate expansion in the patient’s circulation which persists for at least two weeks, the company said.