Core Insights - The SACHI Phase III study demonstrated that the combination of savolitinib and osimertinib significantly improves progression-free survival (PFS) in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC) with MET amplification compared to chemotherapy [1][4][9] Study Overview - SACHI is a Phase III clinical trial focusing on the combination of savolitinib and osimertinib for treating patients with locally advanced or metastatic EGFR mutation-positive NSCLC with MET amplification after progression on first-line EGFR inhibitor therapy [2] Efficacy Results - In the intention-to-treat population, the median PFS was 8.2 months for the savolitinib plus osimertinib group versus 4.5 months for the chemotherapy group, with a hazard ratio (HR) of 0.34 [4] - The independent review committee assessed median PFS at 7.2 months for the combination therapy compared to 4.2 months for chemotherapy, with an HR of 0.40 [4] - The objective response rate (ORR) was 58% for the combination group compared to 34% for chemotherapy, and the disease control rate (DCR) was 89% versus 67% [5] Safety Profile - The combination therapy exhibited a tolerable safety profile, with treatment-emergent adverse events of Grade 3 or above occurring in 57% of patients in both the savolitinib plus osimertinib and chemotherapy groups [7][8] Regulatory Status - The Independent Data Monitoring Committee concluded that the study met its primary endpoint of PFS, leading to the conclusion of patient enrollment [9] - A New Drug Application (NDA) for the combination therapy has been accepted and granted priority review by the China National Medical Products Administration (NMPA) [9] Company Background - HUTCHMED is an innovative biopharmaceutical company focused on the discovery and commercialization of targeted therapies and immunotherapies for cancer and immunological diseases [13]

Core Insights - Olema Pharmaceuticals announced preclinical data for OP-3136, a novel small molecule that selectively inhibits KAT6, demonstrating anti-tumor activity in prostate, ovarian, and non-small cell lung cancer models [1][2][5] Group 1: OP-3136 Overview - OP-3136 is an orally available small molecule that targets KAT6, an epigenetic factor involved in various cancers, including breast cancer [4][7] - The Investigational New Drug (IND) application for OP-3136 was approved by the FDA in December 2024, and patient recruitment for the Phase 1 trial is currently ongoing [4][5] Group 2: Preclinical Findings - In preclinical studies, OP-3136 exhibited significant anti-proliferative activity in ER+ breast cancer models and showed robust tumor growth inhibition in ovarian cancer models [4][6] - OP-3136 demonstrated sustained tumor regression in the OVCAR3 ovarian cancer model over a 28-day study period [6] - In the LCLC-97TM1 NSCLC model, OP-3136's tumor growth inhibition was comparable to ribociclib, and the combination of both showed enhanced anti-tumor activity [6] - The 22Rv1 prostate cancer model showed dose-dependent tumor growth inhibition with OP-3136, and when combined with docetaxel, it resulted in improved anti-tumor effects [6] Group 3: Clinical Development - Olema is actively recruiting patients for the Phase 1 trial of OP-3136, exploring its potential as a monotherapy and in combination regimens across multiple solid tumor types [2][5] - The data on OP-3136 will be presented at the 2025 AACR Annual Meeting, highlighting its potential utility in treating challenging cancers beyond breast cancer [5][6]