Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA
| العنوان: | Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA |
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| المؤلفون: | Ghassan K. Abou-Alfa, Stephen Lam Chan, Masatoshi Kudo, George Lau, Robin Kate Kelley, Junji Furuse, Wattana Sukeepaisarnjaroen, Yoon-Koo Kang, Tu V. Dao, Enrico N. De Toni, Lorenza Rimassa, Valeriy Vladimirovich Breder, Alexander Vasilyev, Alexandra Heurgue, Vincent Tam, Kabir Mody, Satheesh Chiradoni Thungappa, Philip He, Alejandra Negro, Bruno Sangro |
| المصدر: | Journal of Clinical Oncology. 40:379-379 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Oncology |
| الوصف: | 379 Background: A single priming dose of T (anti-CTLA-4) added to D (anti-PD-L1) in the STRIDE (Single T Regular Interval D) regimen, formerly T300+D, showed encouraging clinical activity and limited toxicity in a phase 2 uHCC study (Study 22, NCT02519348), suggesting single exposure to T is sufficient to improve upon D activity. HIMALAYA (NCT03298451) evaluated the efficacy and safety of STRIDE or D vs sorafenib (S) in uHCC. Methods: HIMALAYA is an open-label, multicenter, phase 3 study, in which pts with uHCC and no prior systemic therapy were initially randomized to STRIDE (T 300 mg plus D 1500 mg [one dose] plus D 1500 mg every 4 weeks [Q4W]), D (1500 mg Q4W), S (400 mg twice daily), or T 75 mg Q4W (4 doses) plus D 1500 mg Q4W (T75+D). Recruitment to T75+D ceased after a planned analysis of Study 22 showed T75+D did not meaningfully differ from D. The primary objective was overall survival (OS) for STRIDE vs S. The secondary objective was OS noninferiority (NI) of D to S (NI margin: 1.08). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR; RECIST v.1.1), duration of response (DoR), and safety. Results: In total, 1171 pts were randomized to STRIDE (N=393), D (N=389), or S (N=389). At data cutoff (DCO), the primary objective was met: OS was significantly improved for STRIDE vs S (hazard ratio [HR], 0.78; 96% confidence interval [CI], 0.65–0.92; p=0.0035; Table). D met the objective of OS NI to S (HR, 0.86; 96% CI, 0.73–1.03). ORRs were higher for STRIDE (20.1%) and D (17.0%) than for S (5.1%). No new safety signals were identified. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 25.8% (STRIDE), 12.9% (D), and 36.9% (S) of pts. Grade 3/4 hepatic TRAEs occurred in 5.9% (STRIDE), 5.2% (D), and 4.5% (S) of pts. No TRAE of esophageal varices hemorrhage occurred. Rates of TRAEs leading to discontinuation were 8.2% (STRIDE), 4.1% (D), and 11.0% (S). Conclusions: HIMALAYA was the first large phase 3 trial with a diverse, representative uHCC population and extensive long-term follow-up to assess both mono- and combination immunotherapy. D was noninferior to S with favorable safety. The combination of a single priming dose of T plus D in STRIDE displayed superior efficacy and a favorable benefit-risk profile vs S. STRIDE is a proposed, novel, first-line standard of care systemic therapy for uHCC. Clinical trial information: NCT03298451. [Table: see text] |
| تدمد: | 1527-7755 0732-183X 0251-9348 |
| DOI: | 10.1200/jco.2022.40.4_suppl.379 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::543303862facff0bf0429af01727e61a https://doi.org/10.1200/jco.2022.40.4_suppl.379 |
| رقم الانضمام: | edsair.doi...........543303862facff0bf0429af01727e61a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X 02519348 |
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| DOI: | 10.1200/jco.2022.40.4_suppl.379 |