Date: 2014-12-08
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the American Society of Hematology (ASH) Annual Meeting 2014 in San Francisco
Company: Affimed Therapeutics (Germany)
Product: AFM13
Action
mechanism: 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: advanced relapsing/refractory Hodgkin lymphoma
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The 28-patient phase 1 trial was designed to determine the safety profile, maximum tolerated dose (MTD) and pharmacokinetics (PK), and to provide an indication of activity of AFM13. In the dose escalation part, 24 patients received increasing doses of AFM13 ranging from 0.01 mg/kg to 7.0 mg/kg on a weekly dosing schedule for 4 weeks. In addition, 4 patients were treated with 4.5 mg/kg twice a week for 4 weeks. The median number of prior therapies was 6 (ranging from 3 to 11), and 9 out of 28 patients had received brentuximab vedotin prior to enrollment. In the trial, 14 of the 28 patients were refractory to prior therapy
Latest
news: * On December 8, 2014, Affimed, a clinicalstage biopharmaceutical company developing targeted cancer immunotherapies, announced that final clinical analyses of a Phase 1 study with its lead program AFM13 were presented at the American Society of Hematology (ASH) Annual Meeting 2014 in San Francisco, California, in a poster presentation on December 6, 2014. The analyses confirmed results reported to date that AFM13 is well tolerated with a favorable administration profile, demonstrating strong indications of clinical activity through tumor-shrinkage and Natural Killer (NK) cell engagement. In the Phase 1 study reported at ASH, 28 patients with relapsed/refractory Hodgkin lymphoma (HL) received a salvage treatment with escalating doses (0.01-7.0 mg/kg body weight) of AFM13. AFM13 was administered weekly for 4 weeks in the majority of patients. The study was designed to demonstrate safety and tolerability of the antibody. Secondary endpoints included pharmacokinetics (PK), tumor response and pharmacodynamics (PD). * On April 10, 2014, Affimed Therapeutics has announced further results from its phase 1 clinical trial of AFM13 as monotherapy for the treatment of patients with advanced relapsing/refractory (R/R) Hodgkin lymphoma. In the clinical phase 1 study, 28 heavily pretreated patients suffering from R/R Hodgkin lymphoma received infusions of AFM13 with increasing doses in the range of 0.01 mg/kg up to 7 mg/kg. AFM13 was administered once weekly over 4 weeks in the majority of the patients. Primary endpoints were safety and tolerability. Secondary endpoints were pharmacokinetics, pharmacodynamics and clinical efficacy. The data were presented by Max Topp, Professor of Medicine at the University of Wuerzburg, at the AACR Annual Meeting 2014, San Diego, CA, USA, on April 8, 2014. AFM13 binds selectively to NK cells through CD16A (FcγRIIIA); neutrophils carrying CD16B (FcγRIIIB) are not bound. Cytotoxic potency of AFM13 is consistently higher than those of the Fc-enhanced and native anti-CD30 IgGs. Each of the intravenously administered doses of AFM13 was considered safe and well tolerated, a maximum tolerated dose was not reached. AFM13 treatment resulted in a significant increase of activated NK cells in peripheral blood, which was more pronounced at dose levels >= 1.5 mg/kg. Soluble CD30 values decreased during treatment with AFM13; this effect was pronounced in patients receiving dose levels >= 1.5 mg/kg AFM13. Pharmacokinetic data revealed a dose proportional increase of systemic exposure with a half-life of 10-22 hours. Clinical activity was observed over all dose levels and included patients that received prior brentuximab vedotin. Clinical activity was more pronounced at higher dose levels, and all partial responses (PRs) were observed at doses >= 1.5 mg/kg. * On June 24, 2013, Affimed Therapeutics has announced encouraging results from a phase 1 clinical trial of AFM13 as monotherapy for the treatment of patients with advanced relapsing/refractory Hodgkin lymphoma. AFM13 appears to be well tolerated with evidence of meaningful anti-tumor activity, including partial responses and stable diseases. The data were presented by Andreas Engert, Professor of Medicine at The University of Cologne and Chairman of the German Study Hodgkin\'s Group (GSHG) at the 12th International Conference on Malignant Lymphoma, Lugano, Switzerland. The 28-patient phase 1 trial was designed to determine the safety profile, maximum tolerated dose (MTD) and pharmacokinetics (PK), and to provide an indication of activity of AFM13. AFM13 was safe and well tolerated in the phase 1 study, without reaching the MTD. One dose-limiting toxicity (DLT) was observed at 0.5 mg/kg and this dose level was increased to 6 patients. No further DLTs were observed. The most frequent adverse events were infusion-related reactions (headache, fever, fatigue and myalgia) that often occurred after the first administration. Nearly all adverse events were short-lived. AFM13 induced dose-dependent reduction of shed CD30 antigen and activation of NK cells. According to the Cheson criteria, 2 patients achieved partial responses and 14 patients had stable disease. AFM13 exhibited activity in brentuximab vedotin relapsing/refractory patients with 7 out of 9 patients achieving stable disease after AFM13 treatment. 13 patients received AFM13 as dose levels at and above 1.5 mg/kg. The drug showed substantial anti-tumor activity in these patients with 8 out of the 13 patients exhibiting a reduction in both, tumor volume (as assessed by CT scan) and tumor activity (as assessed by FDG-PET scan imaging). Furthermore, 3 out of 13 patients (23%) exhibited a reduction in tumor volume of more than 50%.
The clinical data demonstrate that AFM13 is very well tolerated. Adverse events are generally mild to moderate. No relevant hematological or neurological events were observed. PK data confirm that the bispecific TandAb molecule can be administered by regular infusions and does not require continuous infusions. Furthermore, AFM13 showed clear activity and more than half of the patients had tumor shrinkage. AFM13 was also active in brentuximab vedotin failures. In peripheral blood, the portion of activated NK cells increased significantly after each infusion and soluble CD30 wasreduced during the treatment period. A Phase 2 proof-of-concept study, conducted by the German Hodgkin Study Group and supported by the Leukemia and Lymphoma Society, is currently in preparation and will commence early 2015.
