Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

A phase 1b study of E7386, a CREB-binding protein/β-catenin interaction inhibitor, plus lenvatinib in patients with advanced hepatocellular carcinoma (HCC) (#217)

Masafumi Ikeda 1 , Naoya Kato 2 , Shunsuke Kondo 3 , Yoshitaka Inaba 4 , Kazuomi Ueshima 5 , Mitsuhito Sasaki 1 , Hiroaki Kanzaki 2 , Hiroshi Ida 5 , Hiroshi Imaoka 1 , Yasunori Minami 5 , Shuichi Mistunaga 1 , Naoshi Nishida 5 , Sadahisa Ogasawara 2 , Kazuo Watanabe 1 , Takatoshi Sahara 6 , Nozomi Hayata 6 , Shintaro Yamamuro 6 , Takayuki Kimura 7 , Toshiyuki Tamai 6 , Chunyan Ma 8 , Masatoshi Kudo 5
  1. National Cancer Center Hospital East, Kashiwa, Japan
  2. Graduate School of Medicine, Chiba University, Chiba, Japan
  3. National Cancer Center Hospital, Tokyo, Japan
  4. Aichi Cancer Center Hospital, Nagoya, Japan
  5. Kindai University Faculty of Medicine, Osaka, Japan
  6. Eisai Co. Ltd, Tokyo, Japan
  7. Eisai Co. Ltd, Ibaraki, Japan
  8. Eisai Australia Pty Ltd, Melbourne, Victoria, Australia

Background: The objectives of the dose-escalation part of this study (NCT04008797) included safety/tolerability, pharmacokinetics, biomarkers, and preliminary efficacy of E7386 (a novel oral anticancer agent modulating Wnt/β-catenin signaling) plus lenvatinib in patients with HCC or other solid tumors. We present results from the HCC subpart.

Methods: In cycle 0, E7386 was administered orally in escalating doses QD or BID for 5 or 6 consecutive days. From cycle 1, E7386 QD or BID, plus daily oral lenvatinib (<60 kg: 8 mg; ≥60 kg: 12 mg), were administered in 28-day cycles. TEAEs were graded using CTCAE v5.0. Prophylactic antiemetics were not allowed during DLT evaluation but were permitted after nausea/vomiting. Tumor response was assessed by investigators using mRECIST.

Results: By data cutoff (9 December 2022), 25 patients with HCC were treated with E7386 doses ranging from 10-80mg QD and 60-120 mg BID. Among the E7386 120 mg BID cohort (n=3), grade 3 maculopapular rash (1 patient) and grade 5 acute kidney injury (1 patient) DLTs were observed. No other DLTs were observed. The most common TEAEs across cohorts were nausea (76.0%), vomiting (60.0%), constipation (52.0%), palmar-plantar erythrodysesthesia syndrome (48.0%), diarrhea (44.0%), and proteinuria (40.0%). The most common grade ≥3 TEAEs were proteinuria (20.0%) and aspartate aminotransferase level increased (8.0%). Nausea and vomiting were well controlled by a 5HT3 antagonist. Among treated patients, 9 (36.0%) partial responses (PRs) were observed, including 3 PRs in 10 patients previously treated with lenvatinib. Cmax and AUC for E7386 increased with increasing E7386 dose.

Conclusions: E7386 100 mg BID plus lenvatinib (8/12 mg QD per bodyweight) was deemed the recommended phase 2 dose in HCC, was tolerable and manageable with antiemetics, and showed promising activity, including in patients pretreated with lenvatinib.


  1. © 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.