Fruquintinib in combination with camrelizumab and paclitaxel liposome and nedaplatin as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, phase II study.

4042 Background: Previous studies have indicated a synergistic effect of fruquintinib in combination with chemotherapy or immunotherapy. Therefore, we conducted a phase II study to evaluate the efficacy and safety of fruquintinib plus camrelizumab, paclitaxel liposome, and nedaplatin as a first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). Methods: This study consisted of a dose-finding and a dose-expansion phase. A total of 33 to 36 eligible patients with untreated advanced ESCC were planned for enrollment. In the dose-finding phase, based on a standard 3+3 design, patients were treated with fruquintinib (3 mg, 4 mg, 5 mg, days 1-14, every 3 weeks, respectively, the initial fruquintinib dose was 4mg), in combination with a fixed dose of camrelizumab 200 mg, paclitaxel liposome 135 mg/m 2 , and nedaplatin 70 mg/m 2 on day 1, every 3 weeks. In the dose-expansion phase, patients received camrelizumab, paclitaxel liposome, nedaplatin and recommended phase 2 dose (RP2D) of fruquintinib. A maximum of six cycles was administered, followed by maintenance therapy with fruquintinib in combination with camrelizumab. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and safety. Results: As of December 28, 2024, 22 patients (20 males) were enrolled with a median age of 65 years (range 50-76). Among the 21 patients with metastases, 19.0% (4/21) had a single metastatic site and 81.0% (17/21) had multiple metastatic sites. In the dose-finding phase, no DLTs occurred in 3 patients at 4 mg and 6 patients at 5 mg, establishing fruquintinib’s RP2D as 5 mg. Of the 19 patients evaluable for efficacy, 13 achieved a partial response, and 6 had stable disease. The confirmed ORR was 68.4% (95% CI: 47.5%-89.3%) for all evaluable patients and 68.8% (95%CI: 41.3%-89.0%) for patients receiving 5 mg dose of fruquintinib. The confirmed DCR was 100.0% (95%CI: 82.4%-100.0%). At a median follow-up of 5.1 (95%CI: 4.2-7.2) months, the median PFS was 8.7 (95%CI: 5.2-not available [NA]) months, the 6-month PFS rate reached 81.7%. The most common treatment-related adverse events (TRAEs) were anemia 72.7% (16/22), neutropenia 40.9% (9/22), leukopenia, hypertension 31.8% (7/22). Grade≥3 TRAEs were identified in seven patients, including neutropenia 13.6% (3/22), leukopenia 13.6% (3/22), oral mucositis 9.1% (2/22), nausea 4.5% (1/22), vomiting 4.5% (1/22), headache 4.5% (1/22), and anemia 4.5% (1/22). No treatment-related serious adverse events (TRSAEs) or deaths occurred. Conclusions: The combination of fruquintinib, camrelizumab, paclitaxel liposome, and nedaplatin demonstrated significant efficacy and manageable toxicity profile as a first-line treatment for advanced ESCC, suggesting a potential new treatment strategy. Clinical trial information: NCT06010212 .