Phase 1 Study of Neratinib and Trastuzumab Deruxtecan for Treating Advanced Solid Tumors with HER2 Changes

What this Trial Is About

Researchers are evaluating the safety, side effects, and best dose of a combination of two anti-cancer drugs, neratinib and trastuzumab deruxtecan, in patients with advanced solid tumors that have spread or cannot be removed by surgery and have changes in the HER2 gene. This phase I trial aims to determine the maximum tolerated dose, assess tumor response, and study the drugs effects on tumor markers and overall survival in this patient population. Participants receive neratinib orally once daily on specified days of each 21-day cycle and trastuzumab deruxtecan intravenously over 30 to 90 minutes on day 1 of each cycle. Treatment cycles repeat every 21 days unless disease progression or unacceptable side effects occur. The study includes dose-escalation and dose-expansion phases, with possible tissue biopsies at various points to evaluate tumor changes and drug impact. Throughout the study, participants undergo blood sample collection, CT scans, and heart function tests via echocardiography or MUGA scans. Biopsies may be performed at baseline, during the study, or at disease progression depending on the cohort. After treatment ends, patients are followed every three months for at least one year to monitor health and survival outcomes. Researchers measure treatment safety, tumor response rates, duration of response, progression-free survival, and drug concentrations over this period.

Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene