88P - Sintilimab plus anlotinib as second-line therapy for metastatic or recurrent gallbladder carcinoma (GBC): A single-arm, phase II study

Background

Gemcitabine plus cisplatin (GC) is currently the standard regimen for advanced biliary tract cancers (BTC), but its effectiveness remains to be improved. PD-1 blockade and chemotherapy have demonstrated important therapeutic advantages in BTC (TOP-AZ). Further, the addition of PD-1 to anlotinib has improved the clinical results in the second-line therapy for additional carcinomas, including cervical cancer and HCC, for which therapeutic options have been limited. The effectiveness and safety of sintilimab plus anlotinib in treating metastatic or recurrent GBC are being evaluated in this study.

Methods

This is a single-arm, phase II trial. Patients with histopathologically confirmed metastatic or recurrent (T2-T4, N0-N+M0-1) GBC, who had previously received S-1 or gemcitabine based chemotherapy were enrolled. Sintilimab (200mg, iv, d1) was given every 3 weeks for up to 2 years, in combination with anlotinib (12mg, po, di-14). The primary endpoint was objective response rate (ORR) and secondary endpoints included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), as well as safety and tolerability.

Results

Between 11/2020 and 5/2022, 13 patients were enrolled with a median age of 63 years (range 51-71), 53.8% were male, and all had an ECOG PS of 0. All of the patients were diagnosed with stage IVB, with 53.8% having distant metastasis. At median follow-up duration of 8.3 months (range 3.2-14.5), ORR was 53.8% in 13 evaluable patients and DCR was 76.9%. The 2 of 13 (15.4%) achieved a complete response (CR), and 5 (38.5%) achieved a partial response (PR). At the first stage of statistical hypothesis, the 2 of 18 achieved CR or PR. Median PFS was 7.3 months (95% CI 3.0-NR), and median OS was 10.2 months (95% CI 6.0-NR). The treatment-related Grade 3/4 AE was pneumonia (7.7%). The most common TRAEs were hand-foot syndrome (30.8%), diarrhea (23.1%), hypothyroidism (23.1%), and oral mucositis (23.1%).

Conclusions

Given the encouraging ORR and tolerable safety, the regimen of sintilimab plus anlotinib may be a viable and safe option for second-line metastatic or recurrent GBC treatment.

Clinical trial identification

Trial protocol number: ChiCTR2000039606 release date: 2020/11/03.

Editorial acknowledgement

Legal entity responsible for the study

Dongfang Hepatobiliary Surgery Hospital of Naval Medical University.

Funding

Innovent Biologics (Suzhou) Co. Ltd.

Disclosure

All authors have declared no conflicts of interest.