Phase (Ph) 1/2a study of CLN-081 in patients (pts) with NSCLC with EGFR exon 20 insertion mutations (Ins20).

作者：Helena Alexandra Yu, Daniel Shao-Weng Tan, Egbert Frederik Smit, Alexander I. Spira, Ross Andrew Soo, Danny Nguyen, Victor Lee, James Chih‐Hsin Yang, Vamsidhar Velcheti, John M. Wrangle, Mark A. Socinski, Marianna Koczywas, David Witter, Asher N. Page, Leigh S. Zawel, John Edward Janik, Zofia Piotrowska · 发表于：Journal of Clinical Oncology · 年份：2022 · DOI：10.1200/jco.2022.40.16_suppl.9007 · 被引用次数：32 · 研究领域：Lung Cancer Treatments and Mutations、Radiomics and Machine Learning in Medical Imaging、Colorectal Cancer Treatments and Studies

9007 Background: EGFR ins20-mutant NSCLC has historically been challenging to treat. While new agents targeting EGFR ins20 have recently been approved, adverse events (AEs), particularly wild type (WT) EGFR-related AEs are common. CLN-081 is a novel EGFR tyrosine kinase inhibitor (TKI) with broad activity against EGFR mutations, including ins20, and increased selectivity for ins20 versus WT EGFR. CLN-081 has been granted FDA Breakthrough Therapy Designation for the treatment of pts with EGFR ins20 NSCLC. We present updated results of the initial multicenter Ph1/2a study of CLN-081 in pts with advanced, EGFR ins20-mutant NSCLC, including 39 pts treated in an expanded cohort at the dose of 100 mg twice daily (BID). Methods: Ph1 dose escalation utilized an accelerated titration (AT) and rolling six design. Individual cohorts were expanded in Phase 1 and 2a based on prespecified protocol criteria. Pts were required to have received prior platinum-based chemotherapy. Stable, treated brain metastasis (mets) were allowed. CLN-081 is dosed in 21-day cycles. Results: As of 13 December 2021, 73 pts [median age: 65 (36-82), median lines of prior therapy: 2 (1-9), 28 (39%) with a history of brain mets] received CLN-081 at 30 mg (8), 45 mg (1), 65 mg (14), 100 mg (39), and 150 mg (11), all BID. Treatment-related AEs in ≥ 15% of pts were rash (74%), diarrhea (27%), paronychia (25%), fatigue (19%), anemia (18%), dry skin (18%), nausea (16%). Treatment-related Gr ≥ 3 AEs in ≥ 4 % of pts incl...