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e16118 Background: The development of ICIs has promoted a major breakthrough in the field of cancer therapy. A number of patients experience primary or acquired resistance to ICIs based first line therapy. Because of the similar mechanisms, PD-(L)1 inhibitors replacement after PD-(L)1 inhibitors-based therapy resistance is difficult to sustain benefits. Therefore, whether suspending immunotherapy, or maintenance immunotherapy and switching the combination drugs in the follow-up strategy is worth to explore. Regorafenib is an oral multikinase inhibitor that blocks the activity of protein kinases involved in angiogenesis, oncogenesis and metastasis. Besides, regorafenib could regulate the immune microenvironment. This retrospective trial aims to evaluate the efficacy of regorafenib in combinations with previous ICI in advanced HCC patients who failed to previous ICI-TKI treatment. Methods: In this study, eligible patients were advanced HCC, who failed to previous treatment with TKIs and PD-1 inhibitors. 17 patients were received PD-1 inhibitor the same as the first-line treatment (dosage and mode of administration according to instructions) and regorafenib (40, 80, 120mg/m2, po, qd, d1-21) every 4 weeks, until disease progression, intolerable toxicities, or physician/patient withdrawal. The safety and efficacy were assessed by investigators per CTCAE v5.0 and RECIST v1.1, respectively. The primary endpoint was objective response rate (ORR), the secondly endpoints were progression-free survival (PFS), disease control rate (DCR), overall survival (OS), duration of response (DOR) and safety. Results: From Nov 15, 2020 to Jan 31, 2022, 17 patients with advanced HCC, Child-Pugh class A liver disease, and ECOG PS 0-1 (16 male vs. 1 female, 13 second-line recipients vs. 4 third-line recipients, median age of 55 years) had been enrolled. 52.94% of the patients had BCLC stage B and others had BCLC stage C. The median follow-up was 8.8 months (range, 2.7-14.7). Confirmed ORR and DCR were 41.2% and 64.7%, respectively. The median PFS was 5.21 months (95% CI, 2.65-7.77). For 13 second line patients, confirmed ORR and DCR were 46.2% and 69.2%, respectively. Median OS and DOR had not yet been reached. 12 recipients had treatment-related adverse events (TRAEs). Most frequent TEAEs (≥5%) included fatigue (15.8%), diarrhea (15.8%), periodontal disease (10.5%), hypertension (10.5%), albuminuria (5.3%). Grade 3 TRAEs occurred in 3 (17.6%) patients included gastrointestinal bleeding, hand-foot syndrome and albuminuria. No Grade 4 TRAE and new safety signal were identified. Conclusions: Regorafenib plus PD-1 inhibitor showed a promising efficacy with favorable safety in HCC patients with PD-1 inhibitor resistance, especially in the standard second line patients. Moreover, the strategy showed a higher ORR than RESORCE study (46.2% vs. 10.6%).

e16144 Background: Patients with advanced or unresectable BTC have limited treatment options and poor prognosis. The combination of ICIs with chemotherapy has demonstrated promising antitumor activity with manageable safety in the first- or second-line in treatment of patients with advanced or unresectable BTC, but only a subset of patients with BTC derive benefit. The standard systemic treatment for BTC has been gemcitabine (800-1250 mg/m2, i.v., d1 and d8, q3w) in combination with oxaliplatin/cisplatin. The regimen is associated with high frequency of intravenous injection or more hospital days. All above highlights the need for new combinations. Therefore, we conducted a retrospective trial to evaluate ICIs combined with CAPOX (more convenient dosing regimen) in patients with advanced or recurrent BTC who were treatment-naive or failed to previous treatment. Methods: In this study, eligible patients were diagnosed as unresectable advanced or recurrent BTC, therapy-naive or failed to previous treatment with chemotherapy, inhibitors of VEGFR or PD-1/PD-L1. In therapy phase, 28 patients were given with ICIs (dosage and mode of administration according to instructions, d1), oxaliplatin (130 mg/m2, i.v., d1), and capecitabine (1000mg/m2, po, bid, d1-14) every 3 weeks, until disease progression, intolerable toxicities, or physician/patient withdrawal. The safety and efficacy were assessed by investigators per CTCAE v5.0 and RECIST v1.1, respectively. The primary endpoint was progression-free survival (PFS), the secondly endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR) and adverse events (AEs). Results: From Dec 24, 2019 to Aug 6, 2021, 28 patients had been enrolled to receive therapy. The patients were characterized with a median age of 58 years (range 53-79), 75% intrahepatic cholangiocarcinoma (ICC) and 25% gallbladder cancer (GBC), 25% lymph node metastasis, 25% liver metastases, 54% with history of surgery, and 57% with therapy-native. As of Jan 23, 2022, with a median follow-up of 9.0 months (range, 2.1-23.4), safety and efficacy were assessed in 26 evaluable patients, with response of 12 PR and 6 SD. Confirmed ORR and disease control rate (DCR) were 46.2% (95% CI, 27.1%-66.2%) and 69.2% (95% CI, 48.1%-84.9%), respectively. The median PFS, median OS and median DOR were 6.1 months (95% CI, 4.9-7.3), 16.5 months (95% CI, 5.0-28.0) and 5.0 months (95% CI, 2.0-8.0), respectively. Grade 3-4 treatment-related adverse events occurred in 32.1% of patients, with thrombocytopenia and bone marrow depression ranking the most frequent. No new safety signal was identified. Conclusions: In this study, ICIs combined with CAPOX not only showed high level of safety and efficacy, but also provided convenience in the treatment of unresectable advanced or recurrent BTC.