GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, today announced that it has entered into a clinical trial collaboration and supply agreement with Merck to start a clinical study of the combination therapy of GFH925 with ERBITUX® (cetuximab) as a potential frontline treatment among NSCLC patients harboring KRAS G12C mutation in a multi-center Phase Ib/II trial in Europe.
Preliminary data from phase I clinical study (NCT05005234) of GFH925 monotherapy for the treatment of solid tumors were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting; and a favorable safety/tolerability and promising antitumor activity profile was observed in previously treated advanced NSCLC patients with KRAS G12C mutation.
"We are delighted to reach an agreement with Merck in our mutual efforts to move forward the clinical investigation of GFH925/Erbitux combination therapy in a frontline setting for NSCLC, as the GFH925 monotherapy program is making significant progress in China. We appreciate Merck's recognition of our fully integrated capabilities in developing innovative products. We are excited for the opportunity to further evaluate the safety/tolerability, as well as efficacy of this promising combination therapy." said Yu Wang, M.D./Ph.D., Chief Medical Officer of GenFleet.
"This trial collaboration will mark the starting point of GenFleet's multi-regional clinical development in Europe. As we reach an increasing number of milestones in our globalization efforts, we believe our cooperation with Merck will strengthen GenFleet's competitive advantage with differentiated development strategy and efficiency. Through internal discovery and co-development initiatives, we hope to bring more innovative therapies to patients worldwide." said Jiong Lan, Ph.D., Chief Executive Officer of GenFleet.
Under the terms of the agreement, GenFleet will conduct an open-label study of the combination therapy in previously untreated advanced NSCLC patients. Merck will provide clinical drug supplies of cetuximab in this multi-center trial in Europe. The use of cetuximab as a monotherapy or as a combination therapy has not been approved in any country for patients with advanced NSCLC.
About KRAS & GFH925
RAS protein family can be divided into KRAS, HRAS and NRAS categories. KRAS mutation are detected in nearly 90% of pancreatic cancer, 30-40% of colon cancer, and 15-20% lung cancer patients. The occurrence of KRAS G12C mutation subset is more frequently observed than those with ALK, ROS1, RET and TRK 1/2/3 mutations combined.
By covalently and irreversibly modifying the cysteine residue of KRAS G12C protein, GFH925 inhibits the GTP/GDP exchange, an essential step in pathway activation. Preclinical cysteine selectivity studies demonstrated high selectivity of GFH925 towards G12C. Subsequently, GFH925 inhibits the downstream signal pathway to induce tumor cells' apoptosis and cell cycle arrest.
About ERBITUX® (cetuximab)
ERBITUX is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of ERBITUX is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth. Based on in vitro evidence, ERBITUX also targets cytotoxic immune effector cells towards EGFR-expressing tumor cells (antibody-dependent cell-mediated cytotoxicity [ADCC]).