A Multi-Center Phase I Trial of Neratinib and Fam-trastuzumab Deruxtecan in Advanced Refractory Gastric and Esophageal Cancer Patients
Fox Chase Cancer Center
Summary
This is Phase 1 dose finding trial with potential dose expansion to evaluate the safety, toxicity, recommended phase 2 dose (RP2D), and maximum tolerated dose (MTD) of Neratinib plus TDxD using a standard 3+3 dose escalation design in patients with metastatic or unresectable gastro-esophageal cancer that are HER2-overexpressing (IHC 3+ or IHC2+/ISH+) and any other gastrointestinal cancer with HER2 expression with IHC3+. Patients must have progressed or been intolerant of at least one prior line of chemotherapy + HER2 directed therapy.
Description
This is Phase 1 dose finding trial with potential dose expansion to evaluate the safety, toxicity, recommended phase 2 dose (RP2D), and maximum tolerated dose (MTD) of Neratinib plus TDxD using a standard 3+3 dose escalation design in patients with metastatic or unresectable gastro-esophageal cancer that are HER2-overexpressing (IHC 3+ or IHC2+/ISH+) and any other gastrointestinal cancer with HER2 expression with IHC3+. Patients must have progressed or been intolerant of at least one prior line of chemotherapy + HER2 directed therapy. A total of 18 patients will be enrolled with the plan to re…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Patients must have been diagnosed with histologically or cytologically confirmed gastrointestinal cancer (esophagus, stomach, colon, biliary, pancreas or unknown primary likely GI), and been deemed unresectable or have at least one site of metastatic disease 2. Patients must have evaluable or measurable disease by RECIST 1.1 criteria 3. 4.1.3 Patients' tumors must have HER2-overexpressing: 1. (IHC 3+ or IHC2+/ISH+) advanced gastroesophageal cancer (including gastroesophageal junction adenocarcinoma). 2. IHC 3+ for other GI cancers 4. Patients must have received a…
Interventions
- DrugNeratinib Pill
Patients will be enrolled in cohorts of 3 at each dose level of Neratinib (120 mg, 160 mg, 200 mg) daily (days 1 through 21)
- DrugFam-Trastuzumab Deruxtecan-Nxki (TDxD)
standard dosing of TDxD (5.4mg/m2) on day 1of a 21 day treatment cycle
Locations (3)
- Stanford Cancer CenterPalo Alto, California
- Roswell Park Comprehensive Cancer CenterBuffalo, New York
- Fox Chase Cancer CenterPhiladelphia, Pennsylvania