Merck KGaA announces new results for bifunctional immunotherapy M7824 - PharmaTimes
M7824 is an investigational bifunctional immunotherapy that brings together a TGF‑β trap and 'fuses' it with the anti-PD-L1 mechanism. Designed to simultaneously block the two immunosuppressive pathways, M7824 is thought to control tumor growth by potentially restoring and enhancing anti-tumor responses. M7824 is an important part of a novel combination approach that seeks to harness the power of the immune system and address the tremendously complex nature of difficult-to-treat tumors.
New data presented include the first presentation of results for M7824 in advanced squamous cell carcinoma of the head and neck (SCCHN), biliary tract cancer (BTC) and esophageal cancers (esophageal squamous cell carcinoma [ESCC] and esophageal adenocarcinoma [EAC]). In addition, updated data for M7824 in non-small cell lung cancer (NSCLC) and gastric cancer add to the growing evidence for M7824's clinical anti-tumor activity in a number of challenging cancers.
New data from an ongoing Phase I expansion cohort (32 patients, NCT02517398) showed signs of promising early clinical activity in patients with refractory metastatic second-line SCCHN, especially in HPV-positive SCCHN patients. The overall response rate (ORR) was 15.6%, with a numerically higher ORR in HPV-positive patients (36.4%, 4/11 patients experienced a partial response), with two additional delayed responses resulting in a 54.5% clinical response rate for the HPV-positive population.
At ASCO 2018, data from the dose escalation cohort of a Phase I, open-label study in advanced HPV-associated cancers (including SCCHN) were presented in collaboration with the National Cancer Institute, which showed that M7824 delivered an ORR of 41.7% in HPV-positive tumors. These new data from the SCCHN expansion cohort add to the evidence of encouraging activity in HPV-positive tumors. A total of 11 patients (34.4%) experienced Grade 3 treatment-related adverse events (TRAEs) and no Grade 4 or 5 TRAEs were seen. The most common TRAEs were rash (18.8%), asthenia (15.6%), pruritus (15.6%), hypothyroidism (15.6%), increased alanine aminotransferase (12.5%), increased aspartate aminotransferase (12.5%) and skin neoplasm (12.5%).
Updated results (now with longer follow-up and independent review committee [IRC] assessed data) from an ongoing Phase I trial (NCT02517398) in patients with previously treated, advanced NSCLC, demonstrated an ORR of 37.0% (10/27 patients) and progression free survival of 9.5 months in patients with PD-L1+ tumors (≥1%). In patients with high PD-L1+ expressing tumors (cut-off of ≥80% using the 73-10 assay; ≥80% cut-off with 73-10 assay is most comparable to ≥50% cut-off with the 22C3 test based on internal comparability studies), ORR was 85.7% (6/7 patients). Grade 3 TRAEs occurred in 23 patients (28.8%) and Grade 4 TRAEs occurred in 2 patients (2.5%): hypokalemia and decreased blood magnesium and increased amylase and lipase levels. The most common TRAEs were pruritus (21.3%), maculopapular rash (18.8%), decreased appetite (12.5%), asthenia (11.3%) and rash (10.0%).
New data from an ongoing expansion cohort (NCT02699515) in Asian patients with BTC who had progressed after platinum-based first-line treatment, demonstrated clinical activity with M782...
(All Rights Reserved)