Phase 1 Study of Neratinib and Fam-Trastuzumab Deruxtecan in Advanced Gastrointestinal Cancers with HER2 Overexpression

What this Trial Is About

Researchers are evaluating the combination of Neratinib and Fam-Trastuzumab Deruxtecan TDxD in patients with metastatic or unresectable gastro-esophageal cancer that overexpress HER2, as well as other gastrointestinal cancers with specific HER2 expression. This Phase 1 trial aims to find the safest and most effective doses by studying the safety, toxicity, and recommended dose for future studies in patients who have already undergone prior chemotherapy and HER2-directed therapy. The study focuses on patients whose cancer has progressed or who could not tolerate previous treatments. The trial uses a dose escalation design where patients receive daily oral Neratinib at increasing doses 120 mg, 160 mg, 200 mg over 21-day cycles alongside intravenous TDxD given on day 1 of each cycle at a standard dose of 5.4 mgkg. If needed, dose adjustments are possible to reduce toxicity. The first cycle includes a Neratinib lead-in week before TDxD administration. Treatment cycles repeat every 21 days, and the study carefully monitors side effects, especially gastrointestinal effects such as diarrhea. Participants will undergo regular tumor imaging assessments every three cycles and heart function tests before starting treatment and every 12 weeks during the study. Safety will be closely monitored, especially during the first 28 days to identify dose-limiting toxicities and establish the maximum tolerated dose. The trial plans to enroll 18 patients to define the recommended phase 2 dose and further assess side effects and preliminary treatment response. The study duration for primary outcome measurement is two years, with ongoing monitoring of cancer response and survival outcomes.

Neratinib and Fam-Trastuzumab Deruxtecan in Advanced Gastro-esophageal Cancer Patients