The following is a summary of “Ezabenlimab (BI 754091) plus modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) followed by chemoradiotherapy (CRT) in patients (pts) with stage III squamous cell anal carcinoma (SCCA): Early efficacy endpoint results from the phase II INTERACT-ION study,” published in the January 2024 issue of Oncology by Kim, et al.
Chemo-radiotherapy (CRT) is the established standard for treating locally advanced squamous cell carcinoma of the anus (SCCA). Despite this, up to 50% of patients face recurrence or the necessity for definitive colostomy, highlighting the need for innovative treatment options to enhance patient outcomes.
The combination of modified dose-dense chemotherapy (mDCF) as a first-line treatment for advanced SCCA and anti-programmed death protein-1 (PD-1) immunotherapy has shown efficacy in a subset of chemorefractory SCCA. Both preclinical and clinical evidence support the feasibility and potential benefits of combining mDCF with anti-PD-1 immunotherapy.
The INTERACT-ION study is an open-label, single-arm investigation in treatment-naïve Stage III SCCA patients (T4N0 or TxN+). The study assessed the efficacy and safety of ezabenlimab (anti-PD-1 antibody) in combination with mDCF as induction therapy, followed by CRT, and maintenance with ezabenlimab. Patients received induction ezabenlimab (240 mg intravenously every 3 weeks for 3 cycles) plus mDCF (D [40 mg/m2], C [40 mg/m 2] on Day 1; F [1200mg/m 2days] every 2 weeks for 4 cycles). Additional cycles were administered if no disease progression occurred after 2 months. Early efficacy analyses were planned after 2 months of treatment. Patients with positive responses received involved nodetumor bed CRT with intensity-modulated radiation therapy (IMRT) followed by 7 cycles of ezabenlimab. The primary endpoint was the clinical complete response (CR) rate 10 months after Cycle 1 of ezabenlimab plus mDCF.
As of the analysis cut-off date, 43 patients had enrolled, with preliminary early efficacy data available for 37 patients. Almost all patients (97.3%) completed the planned 4 cycles of ezabenlimab plus mDCF. One patient experienced treatment-related complications and succumbed to a lung infection. Radiological assessment showed an overall response rate of 97.0%, with 42.4% achieving a complete response. Pathological response data were available for 21 patients, with 76.2% achieving a pathological complete response or near-complete response. Molecular response assessment for human papillomavirus (HPV)+ patients revealed a 91.3% molecular complete response. No safety concerns were identified by an independent safety review committee.
Preliminary findings from the ongoing Phase II study indicated promising antitumor activity and manageable safety for ezabenlimab plus mDCF in treatment-naïve, locally advanced SCCA patients. Further investigation of this novel treatment regimen is warranted to establish its efficacy and safety profile comprehensively.
Source: ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.2
