Tislelizumab In Patients Research Articles

A Phase 1/2 study of the PD-L1 inhibitor, BGB-A333, alone and in combination with the PD-1 inhibitor, tislelizumab, in patients with advanced solid tumours

BackgroundMany patients do not respond or eventually relapse on treatment with programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors due to secondary or acquired resistance; therefore, there is a need to investigate novel PD-1/PD-L1 inhibitors.MethodsThis open-label, non-randomised study investigated the safety and anti-tumour activity of BGB-A333, a PD-L1 inhibitor, alone and in combination with tislelizumab in patients with advanced solid tumours with progression during/after standard therapy. The primary objectives were to determine the recommended Phase 2 dose (RP2D), safety and tolerability for BGB-A333 alone and in combination with tislelizumab (Phase 1a/1b) and to determine the overall response rate (ORR) with BGB-A333 plus tislelizumab (Phase 2).ResultsOverall, 39 patients across Phase 1a (N = 15), 1b (N = 12) and 2 (N = 12) were enroled. In Phase 1a, an RP2D of 1350 mg was determined. In Phase 1a and 1b/2, serious treatment-emergent adverse events (TEAEs) were reported in five and eight patients, respectively. Two patients experienced TEAEs that led to death. In Phase 2, the ORR was 41.7% (n = 5/12; 95% confidence interval: 15.17%, 72.33%).ConclusionsTEAEs reported with BGB-A333 were consistent with other PD-L1 inhibitors. Encouraging preliminary anti-tumour activity was observed with BGB-A333 in combination with tislelizumab.Clinical trial registrationNCT03379259.

Interim result of phase II, prospective, single-arm trial of long-course chemoradiotherapy combined with concurrent tislelizumab in locally advanced rectal cancer.

Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer, with modest benefits on tumor regression and survival. Since chemoradiotherapy combined with immune checkpoint inhibitors has been reported to have synergic effects. This study aims to explore the safety and efficacy of long-course chemoradiotherapy combined with concurrent tislelizumab as a neoadjuvant treatment regimen for patients with locally advanced rectal cancer. This manuscript reported the interim result of a prospective, multicenter, single-arm, phase II trial. Patients with mid-to-low locally advanced rectal cancer with clinical stages of cT3-4a N0M0 or cT1-4a N1-2M0 were included. The patients received long-course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles of capecitabine (1000 mg/m2, bid, day1-14) plus concurrent three 21-day cycles of tislelizumab (200 mg, day8), followed by a radical surgery 6-8 weeks after radiotherapy. The primary endpoint was the pathological complete response rate. (Clinical trial number: NCT04911517). A total of 26 patients completed the treatment protocol between April 2021 and June 2022. All patients completed chemoradiotherapy, 24 patients received three cycles of tislelizumab, and 2 patients received two cycles. The pathological complete remission (ypT0N0) was achieved in 50% (13/26) of the patients with all proficient mismatch repair tumors. The immune-related adverse event occurred in 19.2% (5/26) of patients. Patients with no CEA elevation or age less than 50 were more likely to benefit from this treatment regimen. Long-course chemoradiotherapy combined with concurrent tislelizumab in patients with locally advanced low rectal cancer had favorable safety and efficacy, and does not increase the complication rate of surgery. Further study is needed to confirm these results.

An Open-Label, Phase 1b/2 study of Surufatinib in Combination with Tislelizumab in Patients with Advanced Neuroendocrine Tumors

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

SAFFRON-103: a phase 1b study of the safety and efficacy of sitravatinib combined with tislelizumab in patients with locally advanced or metastatic non-small cell lung cancer

BackgroundSome patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) respond poorly to anti-programmed cell death protein 1 (PD-1)/anti-programmed death-ligand 1 (PD-L1) treatments. Combination with other agents may improve the...

106P Zanubrutinib in combination with tislelizumab in patients with refractory diffuse large B cell lymphoma (DLBCL): A phase II study

Treatment of refractory DLBCL still represents a unique area of unmet need. Previous studies have shown synergistic antitumour effects between Bruton’s tyrosine kinase inhibitors (BTKi) and immune checkpoint inhibitors. However, it lacks data of zanubrutinib and tislelizumab. Herein, we present the premilitary results of an ongoing, multicenter, single-arm phase II study designed to assess the safety and efficacy of zanubrutinib in combination with tislelizumab in refractory DLBCL patients.

74P The safety, tolerability, and preliminary antitumor activity of sitravatinib plus tislelizumab in patients (pts) with locally recurrent or metastatic triple-negative breast cancer (TNBC): A multi-cohort, phase II trial

This is a multi-cohort, phase II trial to evaluate the safety and preliminary antitumor activity of 70 mg (cohort A) or 100 mg (cohort B) sitravatinib QD plus tislelizumab in pts with locally recurrent or metastatic TNBC, and their combination with nab-paclitaxel in untreated locally recurrent inoperable or metastatic TNBC pts (cohort C). The preliminary result of cohort A has been reported with ORR of 38.1% (Lei Fan. JCO 2022 40:16_suppl). This analysis aims to report the updated analysis in cohort A and the interim results in cohort B.

Model-based population pharmacokinetic analysis of tislelizumab in patients with advanced tumors.

Tislelizumab, a humanized immunoglobulin G4 monoclonal antibody, is a programmed cell death protein 1 (PD-1) inhibitor designed to minimize Fc gamma receptor binding on macrophages to limit antibody-dependent phagocytosis, a potential mechanism of resistance to anti-PD-1 therapy. The pharmacokinetic (PK) profile of tislelizumab was analyzed with population PK modeling using 14,473 observed serum concentration data points from 2596 cancer patients who received intravenous (i.v.) tislelizumab at 0.5-10mg/kg every 2 weeks or every 3 weeks (q3w), or a 200 mg i.v. flat dose q3w in 12 clinical studies. Tislelizumab exhibited linear PK across the dose range tested. Baseline body weight, albumin, tumor size, tumor type, and presence of antidrug antibodies were identified as significant covariates on central clearance, whereas baseline body weight, sex, and age significantly affected central volume of distribution. Sensitivity analysis showed that these covariates did not have clinically relevant effects on tislelizumab PK. Other covariates evaluated, including race (Asian vs. White), lactate dehydrogenase, estimated glomerular filtration rate, renal function categories, hepatic function measures and categories, Eastern Cooperative Oncology Group performance status, therapy (monotherapy vs. combination therapy), and line of therapy did not show a statistically significant impact on tislelizumab PK. These results support the use of tislelizumab 200 mg i.v. q3w without dose adjustment in a variety of patient subpopulations.

Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial

Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multiregional phase 2 study RATIONALE-208 examined single-agent tislelizumab (200 mg intravenously every 3 weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by the Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018, and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9–18), including five complete and 27 partial responses. The number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8–20]; two or more prior lines, 13% [95% CI, 7–20]). Median duration of response was not reached. The disease control rate was 53%, and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC.

EP08.01-071 Safety and Efficacy of Sitravatinib + Tislelizumab in Patients with PD-L1+, Locally Advanced/Metastatic, Non-Squamous NSCLC

Patients with programmed death-ligand 1 positive (PD-L1+), locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) have a poor prognosis and treatment options are limited. Sitravatinib, a selective tyrosine kinase inhibitor, reduces the number of myeloid-derived suppressor cells and regulatory T cells, promotes the expansion and migration of antitumor cytotoxic T cells, and increases the ratio of M1/M2-polarized macrophages. Tislelizumab, an anti-programmed cell death protein 1 (PD-1) antibody engineered to minimize binding to FcγR on macrophages, has shown clinical activity in patients with advanced solid tumors, including NSCLC.

EP08.01-073 AdvanTIG-105: Phase 1b Dose-Expansion Study of Ociperlimab plus Tislelizumab in Patients with Metastatic NSCLC

T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) inhibitor plus an anti-programmed cell death protein 1 (PD-1) antibody is a promising combination and shows potent efficacy in non-small cell lung cancer (NSCLC). Ociperlimab is a humanized IgG1 monoclonal antibody (mAb) designed to bind to Fc-intact TIGIT with high affinity and specificity. Tislelizumab is an anti-PD-1 mAb approved for the treatment of NSCLC in China. AdvanTIG-105 is a Phase 1/1b open-label study designed to assess the safety and preliminary antitumor activity of ociperlimab plus tislelizumab in patients with advanced, metastatic unresectable solid tumors (NCT04047862).

EP08.01-070 Safety and Efficacy of Sitravatinib + Tislelizumab in Patients with PD-L1+, Locally Advanced/Metastatic, Squamous NSCLC

Patients with programmed death-ligand 1 positive (PD-L1+), locally advanced or metastatic, squamous non-small cell lung cancer (NSCLC) have a poor prognosis and more effective treatments with better tolerability profiles are needed. Sitravatinib, a selective tyrosine kinase inhibitor, reduces the number of myeloid-derived suppressor cells and regulatory T cells, which promotes expansion and migration of antitumor cytotoxic T cells, and increases the ratio of M1/M2-polarized macrophages. Tislelizumab, an anti-programmed cell death protein 1 (PD-1) antibody engineered to minimize binding to FcγR on macrophages, has shown clinical activity in patients with advanced solid tumors, including NSCLC.

AdvanTIG-202: A phase 2 study investigating anti-T cell immunoglobulin and ITIM domain monoclonal antibody ociperlimab plus tislelizumab in patients with previously treated recurrent or metastatic cervical cancer (333)

AdvanTIG-202: A phase 2 study investigating anti-T cell immunoglobulin and ITIM domain monoclonal antibody ociperlimab plus tislelizumab in patients with previously treated recurrent or metastatic cervical cancer (333)

The safety, tolerability, and preliminary antitumor activity of sitravatinib plus tislelizumab in patients with locally recurrent or metastatic triple-negative breast cancer.

1070 Background: Anti-PD-1 antibody plus chemotherapy has been demonstrated promising anti-tumor activity in patients with locally recurrent or metastatic triple negative breast cancer (TNBC). However, this regime only limited to TNBC patients with PD-L1 positive. As antiangiogenic agents could enhance the response to immune checkpoint inhibitors, we conducted this phase 2 study to assess the efficacy and safety of novel chemotherapy-free regimen of sitravatinib (targets receptor TKI against TYRO3, AXL, MERTK and VEGF family of receptors) in combination with tislelizumab (anti-PD-1 antibody) in patients with locally recurrent or metastatic TNBC regardless of PD-L1 status. Methods: Patients with locally recurrent or metastatic TNBC were included and divided into two cohorts. Patients received 70 mg (cohort A) or 100 mg (cohort B) sitravatinib QD PO and 200 mg tislelizumab IV Q3W until disease progression or intolerable toxicity. The primary endpoints included overall response rate (ORR) (cohort A and B) and rate of grade ≥3 treatment-related adverse events (AEs) (cohort B). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), 1-year overall survival rate and safety/tolerability. In cohort A, the first statistical analysis would be performed when 12 patients were enrolled; if ≥1 of 12 patients were with confirmed response during the first stage, additional 9 patients would be enrolled to the second stage based on Simon's two-stage design. We would deem cohort A to be statistically superior to a historical control of 8% under the settings if > 3 of 21 patients responded (one-sided a = 0.1 and power of 80%). Patients’ recruitment in cohort B would begin after completing the recruitment in cohort A. Results: Herein we reported the preliminary results in cohort A. Four patients were with confirmed response during the first stage, and additional nine patients were enrolled to the second stage. A total of 21 patients with 0-3 lines of prior chemotherapy were included from April 2021 to September 2021. The median age was 51 (32-66) years and 20 (95%) patients had ECOG PS 0. At data cut off 13 Jan 2022, 19 patients were alive, 11 are still on treatment. The confirmed ORR was 38.1% (95% CI, 18.1%-61.6%) based on current 21 efficacy evaluable patients. DCR was 95.2% (95% CI, 76.2%-99.9%), and median PFS was 7.0 (95% CI, 3.7 - not reached) months. 4/21 (19%) of patients experienced grade 3 treatment-related AEs. Grade 3 AEs reported in ≥5% of patients were aspartate aminotransferase increased (9.5%) and palmar-plantar erythrodysaesthesia syndrome (9.5%). No patients experienced grade 4 AEs. Conclusions: Sitravatinib combined with tislelizumab demonstrated clinically meaningful anti-tumor activity and had a manageable safety profile. Clinical trial information: NCT04734262.

P-19 Subgroup analysis of the number of prior lines of systemic therapy and clinical outcomes associated with tislelizumab in patients with previously treated advanced hepatocellular carcinoma (HCC)

Tislelizumab, an anti-programmed cell death protein 1 (PD-1) monoclonal antibody, showed clinical activity and was well tolerated in patients with previously treated advanced HCC in the phase 2 RATIONALE-208 study (NCT03419897). This analysis examined the number of prior lines of systemic therapy and clinical outcomes associated with tislelizumab.

Clinical outcomes associated with tislelizumab in patients (pts) with advanced hepatocellular carcinoma (HCC) who have been previously treated with sorafenib (SOR) or lenvatinib (LEN) in RATIONALE-208.

4072 Background: Tislelizumab, an anti-PD-1 monoclonal antibody, demonstrated clinical activity and was well tolerated in pts with previously treated advanced HCC in the Phase 2 RATIONALE-208 study (NCT03419897). At the time of this study, SOR and LEN were recommended first-line treatments for pts with advanced HCC and continue to have an important role in the first-line treatment of HCC despite the recent approval of new immuno-oncology-based combinations (atezolizumab and bevacizumab) in some regions. We report the clinical outcomes of pts with advanced HCC who were previously treated with SOR/LEN. Methods: Pts who had received ≥ 1 prior line of systemic therapy for advanced HCC received tislelizumab 200 mg intravenously once every three weeks. Objective response rate (ORR) by independent review committee (IRC) (ORRIRC), duration of response by IRC (DORIRC), progression-free survival by IRC (PFSIRC), overall survival (OS), and safety were evaluated in pts who had been previously treated with SOR/LEN. Results: As of February 2020, 249 pts were enrolled and 235 pts had received prior treatment with SOR/LEN, of whom 126 and 109 pts had received 1 or ≥ 2 prior lines of systemic therapy, respectively. At study entry, 211 (89.8%) pts had BCLC stage C and 187 (79.6%) pts had extrahepatic spread. Median follow-up duration for pts previously treated with SOR/LEN was 12.5 months and ORRIRC was 13.6% (95% CI: 9.5, 18.7), including 2 complete responses and 30 partial responses. Median DORIRC was not reached. Median PFSIRC and OS of pts previously treated with SOR/LEN was 2.7 months (95% CI: 1.6, 2.8) and 13.5 months (95% CI: 10.9, 15.8), respectively. Tislelizumab was generally well tolerated in pts previously treated with SOR/LEN (Table), and the most common treatment-emergent adverse events were increased aspartate aminotransferase (n=70; 28.1%) and alanine aminotransferase (n=52; 20.9%). Conclusions: Tislelizumab was investigated beyond the first-line setting, as effective second- and third-line treatment options are limited for pts with advanced HCC and there is an unmet medical need. This analysis indicates that tislelizumab is clinically active and well tolerated in pts with advanced HCC who have received prior systemic treatment with SOR/LEN. Clinical trial information: NCT03419897. [Table: see text]

Selected Articles from This Issue

Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are both characterized by amplification of MDM2 and CDK4. Although inhibitors of both MDM2 and CDK4 have shown clinical promise as monotherapy, preclinical studies have revealed synergy between MDM2 and CDK4 inhibitors. To assess this combination treatment strategy, Abdul Razak and colleagues conducted a clinical trial combining siremadlin, a p53–MDM2 inhibitor, with ribociclib, a CDK4/6 inhibitor, in patients with locally advanced/metastatic WDLPS or DDLPS. The toxicity profile of this combination was manageable. Furthermore, preliminary signs of clinical activity were observed, with 3 patients achieving a partial response and 38 achieving stable disease. These results suggest that the combination of siremadlin and ribociclib should be studied in future clinical trials.The process of autophagy has been shown to lead to resistance to BRAF/MEK inhibition in BRAFV600-mutant melanoma. To investigate whether this resistance mechanism can be circumvented, Mehnert and colleagues conducted a phase I/II clinical trial assessing the combination of hydroxychloroquine (HCQ), an autophagy inhibitor, with dabrafenib and trametinib, in patients with BRAFV600-mutant melanoma. This combination was well tolerated but did not meet a previously determined criteria for success. That said, evidence of clinical activity was observed: a complete response rate of 41% was observed across the entire cohort, while a response rate of 88% was observed in patients with elevated LDH. A follow-up clinical trial is underway to further study this combination in patients with LDH-elevated, BRAFV600-mutant melanoma.Ionizing radiation has been proposed to enhance the efficacy of checkpoint inhibitors. This combinatorial strategy has been shown to be effective in non-small cell lung cancer and other advanced cancer subtypes. To assess the efficacy of this strategy in patients locally advanced rectal cancer (LARC), Bando and colleagues conducted a phase I trial assessing chemotherapy followed by nivolumab and surgery. A pathological complete response (pCR) was observed in 30% and 60% of patients with MSS and MSI-H LARC, respectively. The authors observed elevated PD-L1 levels and CD8+/effector T-reg cell ratio in patients with pCR. Further clinical trials are needed to confirm these results and further establish prognostic biomarkers for this strategy.Tislelizumab is an anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fcγ receptors (FcγR) and subsequent antibody-dependent phagocytosis by macrophages. Song and colleagues conducted an extended three-year follow-up of a phase II clinical trial of tislelizumab in patients with relapsed/refractor classical Hodgkin lymphoma. Tislelizumab remained generally well-tolerated over this extended period. The overall response rate was 87.1%, and the complete response rate was 67.1%, with 3-year progression-free and overall survival rates of 40.8% and 84.8, respectively. Interestingly, FcγRI-positive macrophages did not correlate with CR or PFS. These results are encouraging, warranting further clinical investigation of tislelizumab.

2P Sitravatinib + tislelizumab in patients with metastatic non-small cell lung cancer (NSCLC)

Patients (pts) with advanced NSCLC often develop progressive disease, with limited treatments for pts who are heavily pretreated with anti-PD-(L)1 antibodies and/or chemotherapy. Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM and VEGFR2 receptors, which can reduce the number of myeloid-derived suppressor cells, regulatory T cells, and increases the ratio of M1/M2 polarized macrophages, potentially augmenting antitumor responses. Tislelizumab, is an anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a potential mechanism of resistance.

1P Sitravatinib + tislelizumab in patients with anti-PD-(L)1 refractory/resistant metastatic non-small cell lung cancer (NSCLC)

Patients with metastatic NSCLC who are refractory/resistant (R/R) to anti-PD-(L)1 therapies have limited treatment options. Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM and VEGFR2 receptors, which can reduce the number of myeloid-derived suppressor cells, regulatory T cells, and increase the ratio of M1/M2 polarized macrophages, potentially augmenting antitumor immune responses. Tislelizumab, is an anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a potential mechanism of resistance.

Phase II study of sitravatinib in combination with tislelizumab in patients with advanced biliary tract cancer who have failed to at least 1 prior systemic treatment: Trial in progress.

TPS490 Background: In biliary tract cancer (BTC), there was a positive association of overall survival (OS) with high levels of tumor-infiltrating CD4+, CD8+, and Foxp3+ T lymphocytes, whereas increases in PD-1+/CD8+ tumor-infiltrating lymphocytes had a negative association with OS (Tariq NU et al. 2018). Therefore, immune-modulating treatment can be promising option to overcome a dismal prognosis in BTC patients. However, immune checkpoint inhibitor (ICI) monotherapy, including tislelizumab (anti-PD-1 monoclonal antibody), has a modest effect in advanced BTC (Desai J et al. 2020). Thus, several combination strategies to improve the anti-tumor effect of ICI are being conducted. Anti-angiogenic agent in combination with ICI is one of the promising strategies in which anti-angiogenic agent induced improved anti-tumor immune responses by increasing tumor antigen presentation and promoting lymphocyte infiltration and migration (Song Y et al. 2020). However, this combination have not been widely tested in BTC patients. Sitravatinib is a potent inhibitor of multiple receptor tyrosine kinases including Axl, MER, MET, KIT, FLT3, RET, VEGFR1-3, PDGFRα, which targets are expressed in a number of immune cell types and promote an immunosuppressive tumor microenvironment. This study aim to evaluate the efficacy of the combination strategy of sitravatinib with tislelizumab in advanced BTC and to reveal the immune-modulation through the combination of ICI and antiangiogenic agents. Methods: This study is an open-label, phase 2 study to evaluate the efficacy of sitravatinib and tislelizumab combination treatment in advanced BTC patients who have failed to first-line chemotherapy. Eligible patients have histologically proven BTC (including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer, and ampulla of Vater cancer) and have failed one prior systemic chemotherapy. Patients who have previously received ICI can be enrolled. However, patients who have experienced unacceptable toxicity during prior ICI treatment are excluded. All patients will receive sitravatinib 120mg orally once daily in combination with tislelizumab 200mg intravenously once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is disease control rate, with key secondary endpoints including overall response rate, progression-free survival, overall survival, and safety. For evaluating metabolic response, 18F-FDG PET-CT scan will be performed before treatment and at the first response evaluation. Tissue biopsies will be conducted three times in total: screening, the first response evaluation, and disease progression. Blood samples are being collected every cycles for translational biomarker studies. Clinical trial information: NCT04727996.

Clinical outcomes associated with tislelizumab in patients (pts) with advanced hepatocellular carcinoma (HCC) who have been previously treated with sorafenib (SOR) or lenvatinib (LEN) in RATIONALE-208.

420 Background: Tislelizumab, an anti-PD-1 monoclonal antibody, demonstrated clinical activity and was well tolerated in pts with previously treated advanced HCC in the phase 2 RATIONALE-208 study (NCT03419897). At the time of this study, SOR and LEN were recommended first-line treatments for pts with advanced HCC and continue to have an important role in the first-line treatment of HCC despite the recent approval of new immuno-oncology-based combinations (atezolizumab and bevacizumab) in some regions. We report the clinical outcomes of pts with advanced HCC who were previously treated with SOR/LEN. Methods: Pts who had received ≥1 prior line of systemic therapy for advanced HCC received tislelizumab 200 mg intravenously once every three weeks. Objective response rate (ORR) by independent review committee (IRC) (ORRIRC), duration of response by IRC (DORIRC), progression-free survival by IRC (PFSIRC), overall survival (OS), and safety were evaluated in pts who had been previously treated with SOR/LEN. Results: As of February 2020, 249 pts were enrolled and 235 pts had received prior treatment with SOR/LEN, of whom 126 and 109 pts had received 1 or ≥ 2 prior lines of systemic therapy, respectively. At study entry, 211 (89.8%) pts had BCLC stage C and 187 (79.6%) pts had extrahepatic spread. Median follow-up duration for pts previously treated with SOR/LEN was 12.5 months and ORRIRC was 13.6% (95% CI: 9.5, 18.7), including 2 complete responses and 30 partial responses. Median DORIRC was not reached. Median PFSIRC and OS of pts previously treated with SOR/LEN was 2.7 months (95% CI: 1.6, 2.8) and 13.5 months (95% CI: 10.9, 15.8), respectively. Tislelizumab was generally well tolerated in pts previously treated with SOR/LEN (Table), and the most common treatment-emergent adverse events were increased aspartate aminotransferase (n=70; 28.1%) and alanine aminotransferase (n=52; 20.9%). Conclusions: Tislelizumab was investigated beyond the first-line setting, as effective second- and third-line treatment options are limited for pts with advanced HCC and there is an unmet medical need. This analysis indicates that tislelizumab is clinically active and well tolerated in pts with advanced HCC who have received prior systemic treatment with SOR/LEN. Clinical trial information: NCT03419897. [Table: see text]