Activating the innate immune system to revolutionize the treatment landscape for patients with CD30-positive lymphomas
When discussing Affimed’s pursuit of novel cancer therapies, Adi Hoess, our CEO, recently commented, “Though we know the road to finding a cure for blood cancer is a long one, I’m confident that each milestone we reach in our research brings us closer to our mission of changing the meaning of cancer. That is what motivates us to continue our unrelenting efforts in this vital space.”
Looking at our milestones over the past year, the advances we have made for AFM13, our lead innate cell engager (ICE®) molecule, have demonstrated that Affimed’s approach has the potential to redefine the meaning of cancer.
For many patients with hematologic cancers, which include leukemia, lymphoma and multiple myeloma, additional treatment options are needed because current therapies are not always effective and they can be associated with serious side effects that limit their use. As part of Affimed’s commitment to transforming the treatment of hematologic cancers, we are developing novel ICE® molecules designed to restore the body’s innate immune system to fight cancer. Considered the first line of defense, innate immunity can eliminate tumor cells via natural killer (NK) cells and macrophages.
AFM13, our most advanced ICE® clinical program, represents a novel approach to activating innate immunity. AFM13 binds to both CD16A, a receptor on innate immune cells, such as NK cells and macrophages, and CD30, a receptor found on several types of blood cancer cells. By binding to both innate immune cells and CD30-positive cancer cells, AFM13 redirects the innate immune cells to kill CD30-positive tumor cells.
Clinical data shows promise of treatment with AFM13 in combination with adoptive NK cells
In people with cancer, the ability of their immune system to accurately detect and fight off aberrant cells is suppressed. To address this, our collaborator, The University of Texas MD Anderson Cancer Center, is studying NK cells, derived from cord blood and pre-complexed with AFM13, in a groundbreaking Phase 1 study in patients with recurrent or refractory CD30-positive lymphomas.
Initial safety and efficacy findings from this first-in-human study were presented at the American Association for Cancer Research (AACR) 2021 Annual Meeting. An early analysis of data, conducted in April 2021, showed that all four patients enrolled in the study experienced significant disease reduction – two had a partial response and two had a complete response – with no serious adverse events observed. All of the patients had either relapsed or experienced refractory Hodgkin lymphoma and previously received between 4 and 14 lines of therapy, including anti-PD-1 antibodies and brentuximab vedotin (Adcetris®).
This clinical data, which suggests that pre-complexing AFM13 with adoptive NK cells is an innovative and promising therapeutic approach, built upon preclinical research published in Clinical Cancer Research that showed the combination of NK cells derived from healthy donors and AFM13 was better able to recognize and kill tumor cells than NK cells alone. This preclinical data, generated by a collaboration with MD Anderson Cancer Center and Washington University School of Medicine, also showed that AFM13 strongly binds to cord blood-derived NK cells, resulting in enhanced tumor recognition and cytotoxicity. These findings substantiate the rationale for AFM13 and adoptive NK-cell based combination therapy for CD30-positive hematologic cancers.
Potential of AFM13 as both monotherapy and combination therapy for cancer patients with limited treatment options
The unique properties of AFM13 make it an ideal candidate to be used as monotherapy or in combination with other therapies to potentially provide new treatment options for patients suffering from CD30-positive lymphomas. We are exploring AFM13 as monotherapy in the Phase 2 REDIRECT clinical trial in patients with refractory peripheral T-cell lymphoma (PTCL) or transformed mycosis fungoides (a type of T-cell lymphoma).
We are assessing this ICE® molecule as combination therapy with adoptive NK cells as well as with other immuno-oncology therapies, such as checkpoint inhibitors. Results from a Phase 1b dose-escalation study of AFM13 in combination with the checkpoint inhibitor pembrolizumab in heavily pretreated patients with relapsed or refractory Hodgkin lymphoma showed promising signs of efficacy with an objective response rate of 88% at the highest treatment dose and an 83% overall response rate for the overall population. The combination was generally well tolerated in this proof-of-concept study.
Using AFM13 to unlock the power of the innate immune system presents a novel and promising therapeutic approach to combat hematologic cancer – and is a largely untapped scientific pathway in this field. We believe AFM13 has the potential to transform the field of immuno-oncology by giving patients back their innate ability to fight cancer. We are continuing to develop and customize approaches that leverage the unique and differentiating features of AFM13 to deliver new options for treating a variety of hematologic cancers.
i Bartlett NL, Herrera AF, Domingo-Domenech E, et al. A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2020;136(21):2401-2409. https://ashpublications.org/blood/article/136/21/2401/461621/A-phase-1b-study-of-AFM13-in-combination-with. Accessed August 18, 2021.