Uit het transcript van de conference call gisteren blijkt duidelijk dat AFM24 werkt en dat het in een aantal gevallen al heeft geleid tot disease stabilization. Het aantal patiënten in de cohorts 5 en 6 is uitgebreid. Doordat het veiligheidsprofiel onverminderd gunstig is kunnen de doses zelfs nog verhoogd worden en is de verlenging van de behandeling geen issue. Hoeveel bewijs wil je hebben voor het welslagen van AFM 24?!
"Now, let me turn over to AFM24, our EGFR-directed innate cell engager. For AFM24, we continue to execute our three-pronged strategy of monotherapy, combination with natural killer cells in combination with the checkpoint inhibitor PD-L1. Our goal in this program is to evaluate a broad set of solid tumor indications in parallel supported all by a strong biological rationale. We expect multiple inflection points this year and plan to have multiple additional data readouts in 2022. Our monotherapy dose escalation study is on track. Based on current data, cohorts 5 and 6 are pharmacologically active doses. Therefore, we have increased the size of cohort 5 patients are dosed at 320 milligram and cohort 6 patients are dosed at 480 milligrams to generate additional pharmacokinetic and pharmacodynamic data that we expect will aid our selection of the recommended Phase 2 dose. As of today, in each of the cohorts 5 and 6 – 5 out of 6 patients are enrolled. It is important to mention that to-date in patients that have already completed the DLT period in each cohort. No dose-limiting toxicities were observed.
So as just mentioned, we continue to see a good safety profile of AFM24. We confirm that we have not seen any of the classical EGFR-related target effects like acne form, skin rash or mucosa. This is in line with the distinct mechanisms of action of AFM24, which is very different from the mode of action of EGFR pathway targeting antibodies like cetuximab or panitumumab. These findings also confirm the data from our pivotal toxicology studies in cynomolgus monkeys that indicated a different side effect profile for AFM24 versus cetuximab. Infusion-related reactions remain the main side effect and are well manageable with symptomatic treatment and modifications of infusion rate.
The ongoing dose escalation part includes patients with any EGFR expressed in solid tumors. When assessing anti-tumor activity at dose levels in the 320 milligram and 480 milligram cohort, we are encouraged to see that there were several patients on the study that experienced disease stabilization beyond 8 weeks and we are able to receive additional cycles. Biomarker analysis of the patients point to the activation of effector cells shown by increasing expression of activation markers and a continuous secretion of cytokines, supportive of this observation is a continuous occupancy of the CD16A receptor.
We are enrolling patients in the monotherapy study. And independent of the selection of our recommended Phase 2 dose, we plan to continue to increase the dose in non-selected patients to gather further insight into the exposure, effect relationship of AFM24 focusing on PD markers and to confirm safety of AFM24 at even higher dose levels. Important not to note is in addition in line with our guidance, we expect now to start enrollment of indication-specific patients in the expansion cohorts using single agent AFM24 in the second half of 2021. These cohorts have been chosen based on a detailed analysis of the tumor biology as we explained in the past and will enrich for patients that we believe have a high likelihood to respond to single agent AFM24. These expansion cohorts include – will include renal cell carcinoma that failed standard of care, which includes TKIs and PD-1 targeted therapy. Second indication is non-small cell lung cancer, EGFR-mutant failing standard of care, TKIs. And the third indication is colorectal cancer failing chemotherapy plus EGFR-targeted antigen. So, we have selected three indications for the monotherapy study.
In addition, we are now in the final stages of the setup phase for our combination studies of AFM24 with both atezolizumab, studies called AFM24-102 and the autologous NK cell product, SNK01. The study is called AFM24-103. We confirm our guidance that we expect both of these studies to start enrolling patients in 2021. The tumor types, we plan to study with the AFM24 adhesive combination are as follows. Again, non-small-cell lung cancer, in this case, EGFR wild type failing chemo and PD-1 targeted therapy. Gastric and GEJ cancer failing standard platinum-based chemo and a basket of EGFR-expressing tumors comprising pancreatic, hepatocellular and biliary tract cancer, again failing standard of therapy for the respective study.
Now, the tumor types we plan to study in AFM24, SNK01, NK cell combination studies are as follows: again, non-small-cell lung cancer, EGFR wild type, squamous cell carcinoma of the head and neck failing chemo in PD-1 and colorectal cancer failing standard of care. The indications for each of the three studies have been selected carefully based on the biology of each tumor type. This approach allows us to investigate a broad set of solid tumors while also providing multiple shots on goal for the more prevalent tumor types such as non-small cell lung cancer and colorectal cancer.
In summary, we are very satisfied with the progress of the AFM24 program. The data show that AFM24 possesses a different mode of action compared to conventional EGFR-targeting antibody. We see pharmacological activity based on CD16A receptor binding and NK activation markets. At these pharmacologically active doses, we see no classical EGFR-related side effects like skin or mucosal toxicity. And in addition, we were seeing disease stabilization in these heavily pretreated patients at dose levels 320 milligram and 480 milligram. We believe in the significant potential of AFM24. And with the planned expansion of the program, we are seeking to maximize this opportunity, addressing a broad set of major EGFR-expressing tumor indications. And this strategy will allow us to provide a continuous flow of data."