2973 - mRECIST Outcomes in EMERALD-1: A Phase 3, Randomized, Placebo-Controlled Study of Transarterial Chemoembolization plus Durvalumab with or without Bevacizumab in Participants with Embolization-Eligible

B. Sangro¹, M. Kudo², J. P. Erinjeri³, S. Qin⁴, Z. Ren⁵, S. Chan⁶, Y. Arai⁷, J. Heo⁸, A. Mai⁹, F. E. Penagos¹⁰, Y. A. Lopez Chuken¹¹, J. H. Yoon¹², W. Y. Tak¹³, T. Suttichaimongkol¹⁴, M. Bouattour¹⁵, S. M. Lin¹⁶, M. Zotkiewicz¹⁷, S. Ali¹⁸, G. J. Cohen¹⁹, R. Lencioni²⁰, and M. Hada²¹; ¹Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain, ²Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan, ³Interventional Radiology Service, Memorial Sloan Kettering Cancer Center, New York, NY, ⁴Cancer Center of Nanjing, Jinling Hospital, Nanjing, China, ⁵Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China, ⁶State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Sir Yue-Kong Pao Center for Cancer, The Chinese University of Hong Kong, Hong Kong SAR, China, ⁷Department of Diagnostic Radiology, National Cancer Center, Chuo-ku, Tokyo, Japan, ⁸Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea, Republic of (South), ⁹General Surgery Department, Nhan Dan Gia Dinh Hospital, Ho Chi Minh City, Viet Nam, ¹⁰Hospital San Lucas Cardiológica del Sureste, Chiapas, Mexico, ¹¹I Can Oncology Center, New León, Mexico, ¹²Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea, Republic of (South), ¹³Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea, Republic of (South), ¹⁴Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, ¹⁵Medical Oncology, AP-HP Hôpital Beaujon, Paris, France, ¹⁶Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan, ¹⁷Oncology Biometrics, Late Oncology Statistics, AstraZeneca, Warsaw, Poland, ¹⁸Late Development Oncology, AstraZeneca, Cambridge, United Kingdom, ¹⁹Global Medicines Development, AstraZeneca, Gaithersburg, MD, ²⁰Department of Diagnostic and Interventional Radiology, University of Pisa School of Medicine, Pisa, Italy, ²¹AstraZeneca, Randor, PA

Purpose/Objective(s): Transarterial chemoembolization (TACE) is a standard of care for embolization-eligible unresectable hepatocellular carcinoma (uHCC); however, most people with uHCC treated with TACE progress within one year. The primary endpoint of the Phase 3 EMERALD-1 study (NCT03778957) was positive, with a statistically significant improvement in progression-free survival (PFS) assessed by blinded independent central review (BICR) per RECIST v1.1 with durvalumab (D) + bevacizumab (B) + TACE versus TACE (Table). In addition to RECIST v1.1, efficacy of the regimens was assessed using modified RECIST (mRECIST). The hypothesis was that PFS improvement with D + B + TACE versus TACE was consistent, as assessed per mRECIST and RECIST v1.1. Materials/

Methods: Embolization-eligible participants (pts) were randomized 1:1:1 to receive D + B + TACE, D + TACE, or TACE (cTACE or DEB-TACE per investigator choice). Pts received D (1500 mg) or placebo for D (Q4W) plus TACE. After completion of last TACE, pts received D (1120 mg) plus placebo for B, D (1120 mg) plus B (15 mg/kg), or placebos for D and B (Q3W). PFS was assessed by BICR and the investigator per mRECIST as a secondary endpoint.
Results: PFS improved with D + B + TACE versus TACE as assessed by BICR and the investigator per mRECIST (Table). The estimation of effect was consistent with that of the primary endpoint, which showed a statistically significant improvement in PFS with D + B + TACE versus TACE, as assessed by BICR per RECIST v1.1 (p=0.032, significance threshold 0.0435; Table). D + TACE versus TACE showed similar PFS results as assessed per mRECIST and RECIST v1.1 (Table).
Conclusion: D + B + TACE is the first immune checkpoint inhibitor-based regimen in a global Phase 3 trial to show statistically significant improvement in PFS versus TACE in pts with embolization-eligible uHCC, as assessed by BICR per RECIST v1.1, with consistent PFS results, as assessed per mRECIST. These results further support the potential for D + B + TACE to set a new standard of care in uHCC.

Abstract 2973 – Table 1

	BICR RECIST v1.1 (primary endpoint)			BICR mRECIST			Investigator mRECIST
	D+TACE (N=207)	D+B+TACE (N=204)	TACE (N=205)	D+TACE (N=207)	D+B+TACE (N=204)	TACE (N=205)	D+TACE (N=207)	D+B+TACE (N=204)	TACE (N=205)
Median PFS, months (95% CI)	10.0 (9.0–12.7)	15.0 (11.1–18.9)	8.2 (6.9–11.1)	9.0 (7.0–10.9)	14.2 (11.1–17.4)	8.2 (6.9–9.5)	7.0 (6.7–9.0)	13.2 (9.4–16.4)	7.5 (7.0–9.1)
PFS HR vs TACE (95% CI)	0.94 (0.75–1.19); p=0.638	0.77 (0.61–0.98); p=0.032		0.99 (0.79–1.25)	0.75 (0.60–0.95)		1.03 (0.84–1.28)	0.69 (0.55–0.86)
B, bevacizumab; BICR, blinded independent central review; D, durvalumab; HR, hazard ratio; (m)RECIST, (modified)Response Evaluation Criteria in Solid Tumors; PFS, progression-free survival; TACE, transarterial chemoembolization.