The NCCN Oncology Research Program (ORP) strives to improve the quality of life for patients and reduce cancer-related deaths by advancing cancer therapies through research. Since the program’s establishment in 1999, the NCCN ORP has brought millions of dollars in research grants to investigators at NCCN Member Institutions. Research grants are provided to NCCN through collaborations with pharmaceutical and biotechnology companies; these grants are in turn used to support scientifically meritorious cancer research efforts.
NCCN ORP studies typically explore new avenues of clinical investigation and seek answers to important cancer-related questions. All studies are approved and funded through a scientific peer-review process and are overseen by the ORP.
This feature highlights an NCCN study funded through the grant mechanism.
A Phase II Study of Neratinib in Combination With Chemotherapy/Trastuzumab/Pembrolizumab in HER2-Overexpressing Gastroesophageal Cancers
Principal Investigator: Dae Won Kim, MD
Condition: Stage IV HER2-overexpressing gastroesophageal cancers
Institution: H. Lee Moffitt Cancer Center and Research Institute
This is an open-label, nonrandomized, single-arm, multi-institution phase II study evaluating neratinib in combination with 5-fluorouracil, oxaliplatin, trastuzumab, and pembrolizumab as first-line therapy in patients with metastatic HER2-positive gastric/gastroesophageal junction adenocarcinoma.
Patients with measurable metastatic HER2-positive gastroesophageal adenocarcinomas (GEAs) who have not received prior treatment for metastatic disease will be eligible for inclusion. The study will begin with a lead-in phase in which the first 6 patients will be evaluated for toxicity. If no dose-limiting toxicities (DLTs) are observed, the phase II portion will include a total of 30 patients, including those from the lead-in phase, to assess efficacy. If any DLTs occur during the lead-in phase, dose level −1 will be used for further toxicity evaluation before proceeding to phase II. All patients will receive standard-dose modified FOLFOX (mFOLFOX)/trastuzumab every 2 weeks and pembrolizumab every 6 weeks. Neratinib will be administered orally daily with food. Tumor assessment imaging will be performed every 8 weeks, coinciding with the start of every third cycle. Patients can continue treatment on the study for up to 2 years.
Primary Objective:
• Determine the efficacy of neratinib in combination with mFOLFOX/trastuzumab/pembrolizumab in patients with stage IV HER2-positive GEAs as measured by objective response rate
Secondary Objectives:
• Establish safety of neratinib in combination with mFOLFOX/trastuzumab/pembrolizumab in patients with stage IV HER2-positive GEAs
• Observe other measures of efficacy of neratinib in combination with mFOLFOX/trastuzumab/pembrolizumab, including clinical benefit rate and duration of response, in patients with stage IV HER2-positive GEAs
• Assess median overall survival with neratinib in combination with mFOLFOX/trastuzumab/pembrolizumab in patients with stage IV HER2-positive GEAs
Contact: Dae Won Kim, MD • daewon.kim@moffitt.org
Coordinator: Lauren Ponto • lauren.ponto@moffitt.org
ClinicalTrials.gov Identifier: NCT06109467