Trastuzumab Plus Gedatolisib Demonstrates Promising Efficacy, Safety Among Patients With HER2-Positive Metastatic Breast Cancer
According to results from the phase 2 KM-10A/KCSG BR18-13 study, trastuzumab plus gedatolisib demonstrated promising efficacy and safety among patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer.
These data were first presented by KyongHwa Park, MD, PhD, Korea University College of Medicine, Seoul, South Korea, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.
In this single-arm study, researchers enrolled 44 patients with PI3K pathway genomic aberrations who experienced disease progression on or after at least 2 lines of HER2-directed therapies to receive trastuzumab plus gedatolisib. The primary end point was overall response rate (ORR). Key secondary end points included disease control rate, progression-free survival (PFS), overall survival (OS), and safety. The target enrollment of the study was 62 patients, however the study was prematurely terminated due to drug supply issues regarding gedatolisib.
At analysis with 44 evaluable patients, there were 2 complete responses, 17 partial responses, 19 patients with stable disease, 5 patients with progressive disease, and 1 patient that was non-evaluable, leading to an ORR of 43.2% and a disease control rate of 86.4%. Median PFS was 5.8 months, and median OS was 18.4 months. Frequently-observed grade ≥3 treatment-related adverse events included oral mucositis, skin reactions, and hyperglycemia. No treatment-related deaths were reported, however 22 deaths occurred.
“In this phase II study, the combination of trastuzumab-pkrb and gedatolisib demonstrated a 43.2% response rate with manageable toxicity in patients with HER2 positive [metastatic breast cancer] and PIK3CA mutations,” concluded Dr Park et al. “A translational research study focused on the analysis of cfDNA and [peripheral blood mononuclear cells] is currently being planned.”
Source:
Kim JW, Park YH, Ahn HK, et al. Phase II study of trastuzumab-pkrb plus gedatolisib in patients with HER2-positive metastatic breast cancer who progressed after 2 or more HER2-directed chemotherapies (KM-10A/KCSG BR18-13). Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 1021
