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.

Abstract

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]

A GLOBAL CONGRESS DIGEST ON SOLID TUMORS. Report from the ASCO Hybrid Congress , 3rd – 7th June 2022

“…Efficacy and safety of the anti-PD-1 inhibitor sintilimab have been demonstrated in several malignant entities [11], both in advanced disease like recently shown in esophageal squamous cell carcinoma [12], and in the neoadjuvant setting [13]. In gastric cancer, sintilimab plus XELOX (capecitabine plus oxaliplatin) has demonstrated efficacy after neoadjuvant chemotherapy [14], while lymphocyte-activation gene 3 (LAG-3) -an immune checkpoint receptor protein -controls T-cell response, activation, and growth [15]. Thus, a dual inhibition with anti-PD-1 and anti-LAG-3 might act synergistically against tumoral cells [16].…”

“…Camrelizumab -a programmed cell death 1 (PD-1) inhibitor -has been investigated as treatment of various malignancies and has demonstrated a significantly improved OS or PFS when administered in combination with chemotherapy in phase 3 trials among patients with advanced or metastatic esophageal squamous cell carcinoma [12] or NPC [13]. Famitinib -a receptor tyrosine kinase inhibitor -showed a prolonged PFS in refractory patients with metastatic colorectal cancer when administered as monotherapy [14], and a potent and enduring antitumor activity when combined with camrelizumab in patients with advanced or metastatic renal cell carcinoma [15].…”

“…At ASCO 2022 meeting, the response rate (interim analysis) was presented [14]. Of the 80 evaluable patients in the Nimo+CCRT arm 26 patients achieved a complete response (CR) compared to 10 out of 82 evaluable patients in the Place-bo+CCRT arm (CR-rate, 32.5 % vs 12.2 %; p=0.002); 49 patients had a partial response (PR) in both groups, while four patients reached a stable disease (SD) in the Nimo+CCRT arm (versus 16 patients in the Placebo+CCRT arm) (Figure 2).…”

“…Although chimeric antigen receptor (CAR-T) therapy has proven efficacy in hematologic malignancies [14], there has been limited success in solid tumors [15]. The first clinical candidate from the CoupledCar® solid tumor platform has been introduced -GCC19CART.…”

“…As first-line treatment for advanced HCC, sorafenib (SOR) or lenvatinib (LEN) continue to be an important part of the clinical armamentarium, even considering recent approval of new immune-oncologybased combinations (e.g., atezo lizumab and bevacizumab). In the open-label, multicenter, phase II RATIONALE-208 study (NCT03419897), tislelizumab was clinically active and generally well tolerated in patients with previously treated advanced HCC [14]. A descriptive-only secondary analysis of patients with advanced HCC who had been previously treated with at least one prior line of systemic therapy (SOR/LEN) and had received at least one dose of TIS (200 mg, IV, Q3W) was presented at ASCO 2022 meeting [14].…”