Date: 2016-04-21
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting
Company: Affimed (Germany)
Product: AFM13 with checkpoint modulators, including checkpoint inhibitor PD-1
Action
mechanism: monoclonal antibody/immune checkpoint inhibitor/bispecific antibody. AFM13 is a bispecific TandAb®antibody recruiting host NK cells via its CD16A-binding domains to engage and kill CD30-positive malignant cells. TandAbs®, which were invented and developed by Affimed, are tetravalent bispecific antibody formats that have two binding sites for each antigen. They bind to target molecules on the surface of tumor cells and specifically activate immune effector cells such as cytotoxic T-cells or natural killer (NK) cells in the presence of tumor cells. The TandAb® AFM13 is specifically designed to treat CD30-positive malignancies. It targets CD30 on malignant cells and CD16A on NK-cells. The simultaneous binding to both cells leads to an effective lysis of the tumor cells. In cytotoxicity assays, AFM13 has been shown to possess higher potency than antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced CD30 IgGs.
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On April 21, 2016, Affimed, a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, announced the presentation of preclinical data from a combination study of Affimed's lead candidate AFM13 and checkpoint modulators at the American Association for Cancer Research (AACR) 2016 Annual Meeting in New Orleans, LA. Affimed, together with its collaboration partner Stanford University, provided further evidence for a synergy between its CD30/CD16A-specific NK-cell engager AFM13 and an anti-PD-1 antibody, shedding light on the molecular mechanisms underlying AFM13's previously reported tumor cell-killing properties. Affimed expects to initiate a Phase 1b combination clinical trial this quarter and the Company's investigational new drug (IND) application for AFM13 in combination with pembrolizumab has recently been accepted by the FDA and is now active. In the Phase1b study, Affimed will investigate AFM13 in combination with Merck's Keytruda® for treatment of HL patients relapsed or refractory to chemotherapy, including Adcetris™. The trial is designed to assess safety and efficacy and to establish an optimal dosing regimen for the combination therapy. Data from in vivo PDX models with human CD30+ Hodgkin lymphoma (HL) tumors and immune cells derived from the patients' own PBMCs corroborated the previously described enhancement of AFM13 tumor cell lysis through combination with checkpoint modulators. The effect was most prominent for AFM13 in combination with anti PD-1. Tumor size, tumor-infiltrating human lymphocytes, myeloid cells and intratumoral cytokines were evaluated 2, 16 and 30 days after initiation of treatment. When both AFM13 and PD-1 were combined, a strong correlation between inhibition of tumor growth and increasing levels of tumor-infiltrating NK-cells, T-cells, myeloid cells and intratumoral cytokines such as IFN? were observed, indicating a crosstalk between the innate and adaptive immune system. Over the course of the 30-day treatment period, the initial immune response is characterized by infiltration and activation of NK-cells and macrophages driven by AFM13 followed by the adaptive immune response via T-cells and activated dendritic cells driven by the combination. The data presented at AACR strongly indicate that AFM13-mediated tumor infiltration and activation of different immune cell subpopulations is the molecular basis for the higher efficacy observed for AFM13 in combination with anti-PD-1 treatment. * On May 29, 2015, Affimed provided details on preclinical data from a combination study of Affimed’s lead candidate AFM13 with checkpoint modulators, including checkpoint inhibitor PD-1. These data will be presented on Saturday, May 30, at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting being held May 29 – June 2, 2015 in Chicago, IL. The poster titled “CD137 co-stimulation and blocking PD-1 enhances NK-cell-mediated target lysis by CD30/CD16A TandAb AFM13” (Abstract #3050) outlines the results of four preclinical studies developed by Dr. Holbrook Kohrt at Stanford University in PatientDerived Tumor Graft (PDX) mice to analyze Affimed’s AFM13 in combination with checkpoint modulating agents. In this model, which develops actual human tumors, AFM13, a first-in-class natural killer (NK-) cell engager, demonstrated significant synergy in combination with a PD-1 inhibitor. Importantly, these preclinical results were consistent among the four individual studies. Specifically, tumor samples were surgically obtained from four newly diagnosed CD30+ Hodgkin lymphoma patients. These tumors were xenografted into mice and allowed to grow for 28 days before the mice were infused with the respective patient’s peripheral blood mononuclear cells (PBMCs) and treated on a weekly basis with either monotherapy (IgG control, AFM13, anti-CTLA-4, anti-PD-1, or anti-CD137) or a combination regimen (AFM13 plus anti-CTLA-4, anti-PD-1, or anti-CD137). The mice received three weekly treatments via intraperitoneal injection and tumor size was compared between groups on day 58. The mean results for all patients demonstrated: • Of all single agents investigated, AFM13 showed the most potent anti-tumor efficacy. • As single agents, AFM13 and anti-PD-1 were able to demonstrate tumor shrinkage. • Treatment with the combination of AFM13 with an anti-PD-1 resulted in an impressive decrease in tumor volume, in some cases with complete tumor eradication. • As a single agent, AFM13 led to substantial tumor-infiltration of NK-cells, which was enhanced by the combination with anti-CTLA-4, anti-CD137, and anti-PD-1. • Increased number of tumor-infiltrating cytotoxic T-cells, especially with the combination of AFM13 with anti-PD-1 and anti-CTLA-4. Affimed’s approach to redirect NK-cells to the tumor through its CD16A bispecific TandAb-platform is aiming to reestablish the killing mechanism by the innate immune system. As the innate immune system is also the gate keeper of the adaptive immune system, namely the T- and B-cells, this redirection and killing of cancer cells may also be crucial to activating the adaptive immune response. Affimed is presently investigating this clinically with AFM13 as a monotherapy and is planning to initiate a clinical study with AFM 13 in combination with a checkpoint inhibitor.
