Genprex, Inc. announced today that it has enrolled the first patient in a clinical trial evaluating its lead product candidate Oncoprex® in combination with erlotinib (Tarceva®) for late-stage lung cancer patients. Oncoprex is a targeted biologic incorporating the pan-kinase inhibitor TUSC2, which inhibits oncogenic kinases via multiple pathways.
The trial is significant in that it seeks to determine if patients without the EGFR activating mutation as well as patients with the EGFR activating mutation whose cancer has progressed after erlotinib treatment can benefit from the Oncoprex + erlotinib combination therapy. While erlotinib is a blockbuster drug helping many cancer patients worldwide, research shows that the vast majority of patients who have lung cancers without the activating EGFR mutation are unlikely to benefit from erlotinib. Additionally, many patients with the activating EGFR mutation who respond to erlotinib therapy eventually become resistant to the therapy.
The Phase II clinical trial evaluates Oncoprex + erlotinib in late-stage lung cancer patients without an activating EGFR mutation who have received prior chemotherapy or in patients with the activating EGFR mutation whose cancer has progressed after treatment with erlotinib. An initial safety and dose-finding portion of the trial tests four escalating doses of the Oncoprex + erlotinib combination. Approximately 40 patients enrolled in the highest dose cohort will be evaluable for efficacy. The trial is being conducted at The University of Texas MD Anderson Cancer Center.
Research conducted previously at MD Anderson Cancer Center shows significant cancer-killing synergy when Oncoprex is combined with erlotinib and a variety of other kinase inhibitors (TKIs) including EGFR, AKT, PDGFR, and Src targeted agents. Notably, these data show Oncoprex works synergistically with EGFR TKIs, including erlotinib, in multiple cancers without the activating EGFR mutation. Data also demonstrated that when Oncoprex is combined with EGFR TKI therapy in EGFR mutated and TKI resistant cancers, the Oncoprex combination overcomes intrinsic and acquired therapeutic resistance by simultaneously inactivating the EGFR and the AKT signaling pathways in the cancers that have become resistant to EGFR TKI to restore apoptotic pathways. Importantly, synergistic anticancer results were also obtained from studies combining Oncoprex with EGFR TKIs in K-ras mutant cancers, which are generally unresponsive to EGFR TKIs.
A previously reported phase I safety study in 32 late-stage lung cancer patients demonstrated that intravenous Oncoprex was well tolerated as a single agent. The study showed that non-immunogenic Oncoprex nanovesicles safely travel through the patients' bodies to selectively and preferentially target cancer cells with therapeutic doses of TUSC2 in both primary and metastatic tumors. Tumor responses were seen in both primary and metastatic tumors.