Avistone Biotechnology has announced interim results from its ongoing phase 1 study on PLB1004, a novel mono-anilino-pyrimidine small molecule inhibitor of EGFR. The molecule targets exon 20 insertion as well as classical EGFR mutations ExDel19, L858R, and T790M with a high degree of selectivity over wild-type EGFR. PLB1004 was found to be safe and well-tolerated with promising anti-tumor activity in patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations.
The study is a multi-center, open-label, dose escalation, and expansion study conducted entirely in China to assess the safety, tolerability, pharmacokinetics, and anti-tumor effect of PLB1004, administered orally, in patients with advanced NSCLC. At the cutoff date for these interim results, July 31, 2022, a total of 65 patients (32 in escalation and 33 in expansion) had received treatment with PLB1004. Most patients were women (60%) with adenocarcinoma (95%) and good performance status (ECOG 0-1 in 98%). The most frequent treatment-related adverse events included diarrhea, rash, mouth ulceration, elevated serum creatinine, and elevated aspartate aminotransferase. No DLTs were observed at any dose level, and thus an MTD was not determined during cycle 1 of drug administration.
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Beyond Cycle 1, frequent dose interruptions and reductions due to toxicity were observed, and further dose escalation was not attempted above 480 mg QD. Across all dose groups, a total of 38 subjects had EGFR Ex20ins mutations, including 29 at doses ≥ 160 mg QD, among whom 26 completed at least 1 tumor assessment. In these 26 patients, the confirmed best response rate was 57.7% (15/26), and the disease control rate (DCR) was 100% (26/26). Among the 26 patients (≥160mg QD dose level) with EGFR Ex20ins mutation who completed at least one tumor evaluation, 8 patients had brain metastases, and 3 of them had a PR (37.5%).
“PLB1004 appears to be safe and well-tolerated with promising anti-tumor activity in patients with NSCLC harboring EGFR exon 20 insertion mutations,” said Jin-Ji Yang, M.D., Primary Investigator from Guangdong Provincial People’s Hospital. “Avistone is a science-driven, innovative biotechnology company committed to the discovery and clinical development of first-in-class and best-in-class drugs,” said Dr. Hepeng Shi, Chairman, CEO, and Founder of Avistone. “We are proud to share data at this year’s AACR conference for PLB1004, which has best-in-class potential for patients with EGFR NSCLC. We are excited to present these additional data and to highlight the advancements we are achieving for patients with lung cancer.”
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Avistone is a clinical-stage biotechnology company based in Beijing, China, focusing on researching and developing innovative therapies for patients with significant unmet medical needs globally. The company’s core team comprises experienced drug design and clinical development experts, supported by a scientific advisory committee that includes internationally renowned KOLs. Avistone has an extensive pipeline of targeted therapies for molecular drivers of cancer, including two clinical-stage drug candidates and several ongoing programs in the pre-clinical development stage. Electronic copies of the poster presented at the AACR annual meeting are available upon request.
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