Two-Stage Phase II Study of Envafolimab Combined with Endostar and Concurrent Chemoradiotherapy in Treatment of Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: Preliminary Results of Stage 1

Abstract

<h3>Purpose/Objective(s)</h3> Concurrent chemoradiotherapy (CRT) is the standard of care for patients with unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). In the era of immunotherapy, we performed a single-center, open-label phase II study of CRT combined with endostar (inhibitor of tumor angiogenesis) and envafolimab (PD-L1 checkpoint inhibitor) in patients with LA-ESCC. <h3>Materials/Methods</h3> Treatment-naïve patients with LA-ESCC were enrolled. Radiologists evaluated each patient to exclude the risk of esophageal fistula before enrollment. Involved field radiotherapy at doses of 50.4 Gy (1.8Gy QD), two cycles of paclitaxel liposome (150 mg /m²) and carboplatin (AUC=5) Q4W and 5 cycles of endostar (75mg × 48h, QW) were delivered. Envafolimab at 400 mg subcutaneous injection Q4W was started concurrently with CRT and continued for up to 12 cycles. In Stage 1, the primary endpoint was safety and tolerability. Secondary endpoint was objective response rate and the rate of endoscopic complete remission (EsCR) defined as absence of invasive cells in esophagoscopic biopsy. Responses were assessed by positron emission tomography-computed tomography (PET-CT) at baseline, 12 weeks after the CRT, and computed tomography (CT) at 4 weeks after the CRT, every 12 weeks thereafter. The esophagoscopic examination and biopsy were monitored at baseline, after 41.4 Gy radiation, and 1 month after the CRT To evaluate the efficacy. <h3>Results</h3> Between Sep. 8, 2021 and Nov. 15, 2022, 10 patients were enrolled in Stage-1. Treatment-related adverse events (TRAE) occurred in 9 (90%) patients, the most common of which was fatigue (30%), nausea (40%), thrombocytopenia (20%), leucopenia (60%), acute esophagitis (40%), thyroid dysfunction (10%), and Rash (20%). These occurred predominantly at grade 1 or 2 severity. The most frequent TRAE of grade 3 or worse was leucopenia (40%). No patient had pneumonitis, esophageal fistula. There were no deaths or treatment discontinuations due to serious adverse events. CT scan was completed in 10 patients, esophagoscopic examination biopsy in 9 of them, at 4 weeks after the CRT. All patients had a decrease in target lesion size on CT. The objective response rate was 100%. The pathology report of 8 patients revealed no cancerous cells was observed, resulting in an EsCR rate of 88.9%. <h3>Conclusion</h3> In the stage-1, Envafolimab combined with endostar and CRT was well tolerated with manageable toxicity for unresectable LA-ESCC patients. The preliminary results provide a basis for the ongoing stage 2 study. This trial is registered with ClinicalTrials.gov, number ChiCTR2100051606.