Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

A phase 1b trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC): updated results (#364)

Josep Llovet 1 , Richard Finn 2 , Masfumi Ikeda 3 , Max Sung 4 , Ari Baron 5 , Masatoshi Kudo 6 , Takuji Okusaka 7 , Masahiro Kobayashi 8 , Hiromitsu Kumada 8 , Suichi Kaneko 9 , Marc Pracht 10 , Konstantin Mamontov 11 , Tim Meyer 12 , Kalgi Mody 13 , Tomoki Kubota 14 , Corina Dutcus 13 , Kenichi Saito 15 , Abby Siegel 16 , Leonid Dubrovsky 16 , Louise Young 17 , Andrew X Zhu 18
  1. Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, United States
  2. David Geffen School of Medicine, UCLA Medical Center, Los Angeles, California, United States
  3. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
  4. Tisch Cancer Institute at Mount Sinai, New York, United States
  5. Sutter Health/California Pacific Medical Center Research Institute, San Francisco, California, United States
  6. Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
  7. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
  8. Department of Hepatology, Toranomon Hospital, Tokyo, Japan
  9. Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan
  10. Centre Eugène Marquis, Rennes, France
  11. Altay Regional Oncological Hospital, Barnaul, Russian Federation
  12. Royal Free London NHS Foundation Trust, London, United Kingdom
  13. Eisai Inc., Woodcliff Lake, New Jersey, United States
  14. Clinical Research, Eisai Co. Ltd., Tokyo, Japan
  15. Biostatistics, Oncology Business Group, Eisai, Inc., Woodcliff Lake, NJ, USA
  16. Clinical Research, Merck & Co. Inc., Kenilworth, New Jersey, United States
  17. Eisai Australia Pty. Ltd., Melbourne, Australia
  18. Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA

Aims

LEN, a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT, is approved as monotherapy for first-line treatment of uHCC. PEMBRO is an anti-PD-1 monoclonal antibody that has shown significant efficacy as monotherapy in the second-line treatment of HCC. We report updated results from a phase 1b trial of LEN+PEMBRO in uHCC for the first 67 patients enrolled by December 31, 2018.

Methods

104 Patients with BCLC stage B (not amenable for transarterial chemoembolization) or C, Child-Pugh class A, and ECOG PS ≤1 received LEN (bodyweight ≥60 kg: 12 mg/day; <60 kg: 8 mg/day, orally QD) and PEMBRO (200 mg intravenously Q3W). Primary endpoints were safety (dose-limiting toxicities [DLT] part) and efficacy (expansion part).  As no DLTs were reported,  enrollment was expanded to ≈100 patients (expansion part).

Results

Patients received LEN+PEMBRO (DLT part, n=6; expansion part, n=61). At data cutoff (June 30, 2019), 34 (50.7%) patients remained on study treatment. Median duration of follow-up: 11.7 months (95% CI, 7.8─17.6). SAEs occurred in 42 (62.7%) patients with no new safety signals. ORR (including unconfirmed responses; of 44.8%; Table) compared favorably with LEN arm of REFLECT (24.1%1). Median DOR: 18.7 months (95% CI, 6.9-NE).

Conclusions

LEN+PEMBRO demonstrated promising antitumor activity and an acceptable safety. Independent centralized review is in progress. A phase 3 trial (NCT03713593) is ongoing to assess LEN+PEMBRO vs LEN-alone as first-line therapy for patients with uHCC.

Response Parameter, n (%)

LEN + PEMBRO (n = 67)

mRECIST Per Investigator

Objective response rate (CR + PR + unconfirmed PR or CR)a

30 (44.8)

Best Overall Response

     CR

4 (6.0)

     PRa

26 (38.8)

     Stable disease

25 (37.3)

     Progressive disease

6 (9.0)

     Unknown/not evaluable

6 (9.0)

aIncludes unconfirmed partial responses (2 patients).

CR, complete response; mRECIST, modified Response Evaluation Criteria In Solid Tumors2; PR, partial response.
  1. Kudo M et al. Lancet. 2018;391(10126):1163-1173.
  2. Lencioni et al. Semin Liver Dis. 2010;30:52-60.