A phase II trial of a FAK inhibitor combined with albumin-bound paclitaxel and an anti–PD-1/CTLA-4 bispecific antibody for metastatic, recurrent, or persistent gastric-type endocervical adenocarcinoma (GIFT Study).

Abstract

TPS5630 Background: Gastric-type endocervical adenocarcinoma (GAC) is a rare, HPV-independent subtype of cervical cancer with an aggressive clinical course and an exceptionally poor prognosis. Current clinical guidelines offer largely non-specific treatment recommendations, and conventional chemotherapy-based regimens, even when combined with immunotherapy, frequently demonstrate limited efficacy and early resistance in patients with advanced, recurrent, or metastatic disease. Preclinical studies demonstrate that FAK inhibition can remodel the tumor microenvironment and enhance sensitivity to both cytotoxic chemotherapy and immunotherapy. This study aims to evaluate the efficacy and safety of the FAK inhibitor IN10018 in combination with immunotherapy and chemotherapy in patients with GAC. Methods: The GIFT study is a multicenter, open-label, single-arm, prospective phase II trial designed to evaluate the combination of the FAK inhibitor IN10018 with nab-paclitaxel and cadonilimab (a PD-1/CTLA-4 bispecific antibody) in patients with metastatic, recurrent, or persistent gastric-type endocervical adenocarcinoma. A total of 25 eligible patients will receive oral IN10018 (100 mg once daily) in combination with intravenous nab-paclitaxel (260 mg/m²) and cadonilimab (10 mg/kg) on day 1 of each 21-day cycle. Tumor response will be assessed every 6 weeks by imaging according to RECIST v1.1. Patients will receive up to six cycles of combination chemotherapy, followed by maintenance therapy with IN10018 and cadonilimab until disease progression or unacceptable toxicity. The primary endpoint is objective response rate. Secondary endpoints include progression-free survival, disease control rate, and safety. An additional exploratory objective is to longitudinally evaluate alterations in peripheral circulating cell-free DNA and the tumor microenvironment and to examine their association with therapeutic response. The study is currently active and enrolling patients. As of the data cutoff, 14 of the planned 25 patients have been enrolled. The trial is registered at ClinicalTrials.gov (NCT06654011). Clinical trial information: NCT06654011 .