105P A phase II study of SHR-1316 plus IBI310 in patients with advanced intrahepatic cholangiocarcinoma after failure of first-line therapy

Advanced intrahepatic cholangiocarcinoma (iCCA) is highly invasive and holds high mortality due to limited therapeutic strategies after failure of first-line therapy. This study aimed to evaluate the efficacy and safety of anti-PD-L1 antibody SHR-1316 in combination with anti-CTLA-4 antibody IBI310 for patients (pts) with previously treated advanced iCCA. The study was an ongoing open-label, single-arm, phase 2 trial. Unresectable, locally advanced or metastatic iCCA pts who had failed first or subsequent-line therapy were enrolled. A combination of SHR-1316 (IV 20mg/kg q3w) and IBI310 (IV 3mg/kg q3w) were administered for 4 cycles, followed by SHR-1316 monotherapy until disease progression, unacceptable toxicity, or a maximum of 2 years after enrollment. The primary endpoint was objective response rate (ORR). Secondary objectives included safety, overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). Response was evaluated according to RECIST1.1. Adverse effects (AEs) were assessed according to CTCAE V5.0. Up to May 1, 2023, 39 pathologically confirmed advanced iCCA pts were enrolled. Median age was 59 years (range 28 to 74). Previous treatments included systemic chemotherapy (39 pts), anti-PD-1 antibody (21 pts), and tyrosine kinase inhibitors (26 pts). At date cut-off, the median follow-up was 6.1 months (95%CI, 0.2-18.7), 28 pts were alive, 18 pts remained on treatment. Of 25 evaluable pts, 2 pts achieved complete response and 3 had partial response. The confirmed ORR and DCR were 20.0% and 60.0%, respectively. Notably, the ORR for pts previously treated with anti-PD-1 antibody was 16.7% (2/13). Median PFS and OS was not reached yet. Grade 3 or higher AEs occurred in 16 pts (41.0%), most commonly jaundice (15.4%), rash (10.3%), ALT elevation (7.7%), anaphylaxis (7.7%), AST elevation (5.1%), diarrhea (5.1%) and dyspnea (5.1%). The treatment of SHR-1316 combined with IBI310 was tolerable and showed promising antitumor activity in iCCA refractory to standard therapy. Further studies are required to identify predictive/prognostic biomarkers to improve selection of pts most likely to benefit from this treatment strategy.