공시 • May 27
Affimed N.V. Announces Highlights Trial Designs of Three AFM24 Ongoing Clinical Studies At the Annual Meeting of the American Society of Clinical Oncology
Affimed N.V. announced that three abstracts of clinical trial designs of its AFM24 innate cell engager have been published and will be presented at the American Society of Clinical Oncology Annual Meeting, taking place on June 3-7, 2022 in Chicago, IL. The Trial in Progress posters provide background information and introduce the study designs of the three ongoing AFM24 studies in which patients with a variety of EGFR-positive solid tumors are treated with AFM24 monotherapy or in combinations with either Roche’s checkpoint inhibitor, atezolizumab, or NKGen Biotech’s autologous NK cell product, SNK01. Affimed’s ICE® molecules are tetravalent, bispecific and therefore can bind to tumor cell-surface antigens and CD16A expressed on natural killer cells and macrophages, inducing antibody-dependent cellular cytotoxicity and antibody dependent cellular phagocytosis, respectively. AFM24 activates the innate immune system to kill cancer cells by binding to CD16A on innate immune cells and EGFR, a protein widely expressed on solid tumors. AFM24 utilizes the patient’s innate immunity to redirect and activate immune cells, overcoming resistance to current therapies. The primary mode of action of AFM24 is to redirect NK cells and macrophages to EGFR+ tumor cells inducing antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis, respectively. Preclinical studies showed AFM24 induced killing of EGFR+ tumor cell lines independent of EGFR expression level and independent of mutations in the EGFR signaling pathway. In vivo studies in cynomolgus monkeys demonstrated a favourable safety profile. An ongoing phase 1/2a, first-in-human study is evaluating AFM24 in patients with locally advanced or metastatic, treatment refractory solid tumors that are known to express EGFR. The phase 1 dose escalation study was designed to establish the maximum tolerated dose and the recommended phase 2 dose of AFM24 and evaluate the safety, efficacy, immunogenicity, pharmacokinetic and pharmacodynamic responses. AFM24 was administered intravenously once weekly until disease progression, intolerable toxicity, patient withdrawal, or termination of treatment at investigator’s discretion. AFM24 had a well-managed safety profile and the RP2D was established at 480 mg. In parallel to the continuing dose escalation phase, a phase 2a dose expansion study was initiated, and the first patient was enrolled in January 2022. This Simon two-stage study will assess AFM24 at the RP2D in patients with different EGFR-expressing tumors. The trial will progress to the second stage unless the null hypothesis, that the true tumor response rate is below a specific value, is confirmed at the end of stage one. Eligible patients must have positive histological or cytological staining of EGFR in >1% of tumor cells. The primary endpoint of the study is to establish the overall response rate in three disease-specific cohorts. These include patients with clear cell renal cell carcinoma (ccRCC), KRAS wild-type colorectal cancer (KRASwt CRC) and EGFR-mutant non-small cell lung cancer (EGFRmut NSCLC). Secondary endpoints include treatment-emergent adverse events, serious adverse events, PK, PD, and immunogenicity. Anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors which enhance anti-tumor activity of a patient’s adaptive immunity, have already demonstrated efficacy as monotherapy and are playing an increasingly prominent role in cancer treatment. The combination of AFM24 and PD-L1 inhibitor, atezolizumab, may represent a promising new treatment modality, enhancing both the innate and adaptive immune responses to target EGFR+ tumor cells. An ongoing phase 1/2a open-label, non-randomized, multicenter, dose escalation (phase 1) and dose expansion (phase 2) study was initiated in November 2021 to evaluate the safety, tolerability and efficacy of AFM24 in combination with atezolizumab. The primary aim of the phase 1 study is to determine the maximum tolerated dose and the RP2D of AFM24. Eligible patients must have advanced, histologically confirmed EGFR+ disease and confirmed disease progression after treatment with =1 prior therapy. A standard 3+3 design will be used to determine the RP2D. Escalating doses of AFM24 will be given to each cohort as weekly intravenous (IV) infusions. The starting dose and at least two planned dose escalations are based on results from the ongoing AFM24 monotherapy trial. Atezolizumab is given at a fixed dose of 840 mg biweekly IV infusion. Patients will receive AFM24 and atezolizumab treatment until disease progression, intolerable toxicity, patient withdrawal, or termination of treatment at investigator’s discretion. The phase 2a study will establish the overall response rate and safety of the combination therapy in patients with advanced/metastatic, or treatment refractory gastric, esophagogastric, hepatocellular, hepatobiliary, pancreatic, or non-small cell lung cancer. For both phases, secondary endpoints include treatment-emergent adverse events, serious adverse events, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity. The AFM24 combination study with SNK01 autologous natural killer cells (NCT05099549) includes information about the dose-escalation and dose-expansion phase of AFM24 in combination with SNK01 autologous NK cells in patients with advanced EGFR+ solid tumors. Autologous NK cell transfer represents a promising treatment strategy, with ex vivo expansion and activation enhancing the specificity and anti-tumor activity of NK cells. The efficacy of this approach may be enhanced through the addition of tumor-targeting antibodies, augmenting NK-cell mediated ADCC. An ongoing phase 1/2a open-label, non-randomized, multicenter, dose escalation (phase 1) and dose expansion (phase 2) study were initiated in November 2021 to evaluate the safety, tolerability and efficacy of AFM24 in combination with SNK01 autologous NK cells in patients with advanced EGFR+ solid tumors. The primary aim of the phase 1 study is to determine the maximum tolerated dose and RP2D of AFM24 in combination with SNK01 at a fixed dose of NK cells using a standard 3+3 design.
