89P Radiotherapy Followed by Camrelizumab for Unresectable Biliary Tract Cancer: A Phase II Clinical Trial

Unresectable biliary tract cancer (BTC) has a poor prognosis despite treated with the standard combination chemotherapy. We aimed to evaluate the efficacy, safety, and biomarkers of radiotherapy and camrelizumab as first-line therapy in unresectable BTC. In this single-arm, phase II study, patients with histopathologically confirmed unresectable BTC without distant metastases received external radiotherapy with a dose of ≥45 Gy (2-2.5 Gy per fraction), followed by anti-PD-1 immunotherapy (camrelizumab 200mg once, every 3 weeks) initiated within 7 days after completion of radiotherapy as first-line therapy. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included safety, objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Integrated biomarker analyses were also performed. Between December, 2019 and March, 2021, a total of 36 patients with unresectable BTC were enrolled after assessing 50 patients for eligibility. All eligible patients [23 (63.9%) male; median (range) age, 62 (28-75) years] completed radiotherapy and at least one cycle of camrelizumab. With a median follow-up of 19 months (IQR 12-24), the median PFS and OS were 12 months (95% CI, 8-not estimable) and 22 months (95% CI, 15-not estimable), respectively. And the 1-year PFS rate was 44%. The ORR was 61.1% [95% CI, 43.5-76.9], and the DCR was 86.1% [95% CI, 70.5-95.3]. In addition, median OS was prolonged in patients with high of tumor mutational burden (TMB) compared with those with low TMB (24 vs. 15 months, nominal p=0.041). Five (13.9%) patients experienced grade ≥3 treatment-related adverse effects, including decreased lymphocyte (5.6%), bullous dermatitis (2.8%), decreased platelet count (2.8%), and deep-vein thrombosis (2.8%). External radiotherapy followed by camrelizumab indicated an acceptable antitumor activity and low toxicity levels in unresectable BTC without distant metastases as the first-line therapy, the efficacy of this regimen was related to the TMB status, but warranting further investigation.