Sintilimab (anti-PD-1 antibody) combined with chidamide (an oral subtype-selective HDACi) followed by P-GemOx regimen in patients with treatment-naïve extranodal natural killer/T cell lymphoma (TN-ENKTL): A multicenter, open-label, single-arm, phase

7006 Background: ENKTL is a highly aggressive NHL with a higher incidence in Asia. P-GemOx regimen is one of standard first-line treatment with mildly toxicities. We confirmed that Sintilimab plus Chidamide (SC) is safe and efficacious in patients(pts) with relapsed or refractory (r/r) ENKTL in previous study (SCENT trial). Initiation of SC prior to r/r might further optimize pts outcomes. Therefore, we conducted a prospective study to investigate the efficacy and safety of SC followed by P-GemOx for TN-ENKTL (NCT04994210). Here we present the preliminary results of pts with early stage. Methods: This is an investigator-initiated study,eligible pts were aged 18-80 years with histologically confirmed TN-ENKTL. Pts received 2 cycles of SC (SC×2) with standard doses (part A). Once pts had a CR or PR, 2 cycles of P-GemOx (P-GemOx×2) were administered (part B). If they got SD or PR, pts received P-GemOx×4. All pts accepted involved field radiotherapy (IFRT) after part B. The primary endpoint is the CR rate (CRR) of part A+B. Key secondary endpoints include CRR of part A, duration of CR (DoCR), PFS, OS and safety. According to historical data of P-GemOx, we expected a CRR of 80% and a minimum CRR of 60% after part A + B. A sample size of 47 was required. Pretreatment FFPE tumor and blood samples were analyzed by capture-based NGS targeting lymphoma relevant genes. Results: From Aug 2022 to Dec 2024, 47 eligible pts were enrolled from 3 centers in China. Two pts remained on treatment. All pts underwent PET/CT for efficacy evaluation. Across the 46 efficacy-evaluable pts after SC×2, 36 (78.2%) achieved response, including 29(60.3%) CR pts. Median cycles of P-GemOx were 2(1-4). After part B, among the 42 response-evaluable pts, the CRR was 95.2% (40/42), and the ORR was 97.6% (41/42). The median follow-up time was 12.4 (0.2-23.7) months. The 1-year DoCR, PFS, OS rates were 96.2% (95%CI, 75.7-99.5), 97.5% (95%CI, 83.6-99.6), 95.3% (95%CI, 82.2-98.8), respectively. The most common myelotoxicities were neutropenia (97.8%), lymphopenia (89.4%), anemia (74.5%), thrombocytopenia (58.7%), and non-myelotoxicities including appetite (38.3%), nausea (38.3%), lipase increased (31.9%). Most toxicities came from P-GemOx. Three patients died, 2 due to disease progression and 1 due to accident. Tumor DNA data in relation to efficacy will be presented at the meeting. Conclusions: Preliminary results from SCENT-2 trial exceeded expected efficacy. It may be a promising chemo-reduced therapeutic and manageable toxicities for this population. Further investigation is needed. Clinical trial information: NCT04994210 .