Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

A phase 1b trial of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma (uHCC) (#182)

Masafumi Ikeda 1 , Max W Sung 2 , Masatoshi Kudo 3 , Masahiro Kobayashi 4 , Ari D Baron 5 , Richard S Finn 6 , Shuichi Kaneko 7 , Andrew X Zhu 8 , Tomoki Kubota 9 , Silvija Kraljevic 10 , Kohei Ishikawa 9 , Abby B Siegel 11 , Hiromitsu Kumada 4 , Louise Young 12 , Takuji Okusaka 13
  1. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan
  2. Tisch Cancer Institute at Mount Sinai, New York, USA
  3. Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
  4. Department of Hepatology, Toranomon Hospital, Tokyo, Japan
  5. California Pacific Medical Center, Pacific Hematology Oncology Associates, San Francisco, California, USA
  6. David Geffen School of Medicine, UCLA Medical Center, Losa Angeles, California, USA
  7. Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan
  8. Massachusetts General Hospital, Harvard University, Boston, Massachusetts, USA
  9. Eisai Co., Ltd, Tokyo, Japan
  10. Eisai Ltd, Hatfield, UK
  11. Merck Co. Inc, Kenilworth, New Jersey, USA
  12. Eisai Australia Pty Ltd, Melbourne, VIC, Australia
  13. Department of Hepatobiliary and Pancreatic Oncology, National Cancr Center Hospital, Tokyo, Japan

Aims: Lenvatinib showed noninferiority in overall survival (OS) compared with sorafenib for first-line treatment of patients with uHCC in a phase 3 trial (REFLECT). Pembrolizumab has shown promising activity in HCC. We report preliminary results from a phase 1b trial of lenvatinib+pembrolizumab in uHCC (NCT03006926).

Methods: In this open-label, multicenter study, patients with uHCC, BCLC stage B or C, Child-Pugh class A, and ECOG PS ≤1 received lenvatinib (body weight ≥60 kg: 12 mg/day; <60 kg: 8 mg/day) daily and 200 mg pembrolizumab intravenously Q3W. Dose-limiting toxicities (DLTs) were assessed during Cycle 1 in patients ineligible for other therapies (3+3 design; Part 1). Once tolerability was confirmed, patients with no prior systemic therapy for uHCC were enrolled (Part 2). The primary endpoint was safety. Secondary endpoints included objective response rate using modified RECIST. Tumor assessments were confirmed ≥4 weeks after initial response.

Results: As of December 1, 2017, 18 patients had received lenvatinib+pembrolizumab (Part 1: n=6; Part 2: n=12). Patients had BCLC stage B (n=6) or C (n=12), Child-Pugh scores of 5 (n=14) or 6 (n=4); 4 patients (22%) had received prior sorafenib. No DLTs were reported in Part 1. All 18 patients remained on study. TEAEs occurred in 17 patients (94%); the most common TEAEs were decreased appetite and hypertension (56% each). No new safety signals were identified. Efficacy outcomes are shown below (table). At data cutoff, tumor reduction was observed in all evaluable patients except one.

Conclusion: Lenvatinib+pembrolizumab was well tolerated with encouraging anti-tumor activity in patients with uHCC.


Part 1


Part 2




Best Overall Response, n (%)

   Partial response*

4 (67)

2 (29)

6 (46)

   Stable disease

2 (33)

4 (57)

6 (46)

   Progressive disease

0 (0)

0 (0)

0 (0)

   Not evaluable

0 (0)

1 (14)

1 (8)

*3 Partial responses confirmed.