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.
Authors: Stefano Kim, Jihane Boustani, Dewi Vernerey, Ludovic Evesque, Benoist Chibaudel, Angélique Vienot, Olivier Bouche, Chloé Vernet, Clélia Coutzac, François Ghiringhelli, David Tougeron, Laurent Quero, Laurent Mineur, Aurelién Carnot, Aurelia Meurisse, Magali Rebucci-Peixoto, Sarah Chennoufi, Christophe Maritaz, Christophe Borg
Journal: Journal of Clinical Oncology (2024)

2 Background: CRT is the standard of care for locally advanced SCCA. However, up to 50% of pts experience recurrence/definitive colostomy; there is an unmet need for novel treatment (Tx) options to improve pt outcomes. mDCF is a standard first-line Tx for advanced SCCA, and anti-programmed death protein-1 (PD-1) immunotherapy has been shown to be effective in a subset of chemorefractory SCCA. Preclinical and clinical data support the feasibility and the potential of combining mDCF with anti-PD-1 immunotherapy. Methods: INTERACT-ION (NCT04719988) is an open-label, single-arm study in pts with Tx-naïve Stage III (T4N0 or TxN+) SCCA to evaluate ezabenlimab (anti-PD-1 antibody) plus mDCF as induction therapy, followed by CRT and then maintenance with ezabenlimab. Pts received induction ezabenlimab (240 mg intravenously, every 3 weeks, 3 cycles) plus mDCF (D [40 mg/m 2 ], C [40 mg/m 2 ] on Day 1; F [1200 mg/m 2 /day for 2 days] every 2 weeks, 4 cycles). If there was no disease progression after 2 months, pts received an additional cycle of ezabenlimab plus 2 cycles of mDCF. Planned early efficacy endpoint analyses were performed after 2 months of Tx. Pts with radiological objective response (OR; RECIST v1.1), pathological (p) complete response (CR)/near CR (&lt;10% viable tumor cells) by repeat biopsy, and molecular CR (undetectable human papillomavirus [HPV] circulating tumor DNA) by liquid biopsy, received involved nodetumor bed CRT with intensity-modulated radiation therapy (IMRT) followed by 7 cycles of ezabenlimab. All other pts received standard IMRT based-CRT. The primary endpoint is the clinical CR rate 10 months after Cycle 1 of ezabenlimab plus mDCF. Results: At analysis cut-off date,43 pts had been enrolled; 37 pts had preliminary early efficacy endpoint evaluation. All but 1 pt (97.3%) received the planned 4 cycles of ezabenlimab plus mDCF prior to evaluation; 1 pt presented with treatment-related capillary leak syndrome after Cycle 1 and died of a lung infection 3 months later. Radiological assessment was performed in 33 pts; 32 (97.0%) had radiological OR including 14 (42.4%) with CR. One HPV- pt had disease progression. Pathological response data were available for 21 pts; 16 (76.2%) had pCR/near pCR. For molecular response, 3 pts were HPV- (excluded). Among 23 HPV+ evaluable pts, 21 (91.3%) had a molecular CR. Two pts had a significant decrease at 2 months (decrease: 14/1 and 54/1); then molecular CR after radiotherapy. No safety signals were identified by an independent safety review committee. Conclusions: Preliminary results from this ongoing Phase II study show promising antitumor activity and manageable safety of ezabenlimab plus mDCF in pts with Tx-naïve, locally advanced SCCA. Further evaluation of this new treatment regimen is warranted. Clinical trial information: NCT04719988 .