e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2020

Phase 2 trial of lenvatinib (LEN) + pembrolizumab (PEMBRO) for progressive disease after PD-1/PD-L1 immune checkpoint inhibitor (ICI) in metastatic clear cell (mcc) renal cell carcinoma (RCC): results by independent imaging review and subgroup analyses (#253)

Chung-Han Lee 1 , Amishi Yogesh Shah 2 , James J. Hsieh 3 , Arpit Rao 4 , Alvaro Pinto 5 , Mehmet Asim Bilen 6 , Allen Lee Cohn 7 , Christopher Di Simone 8 , David R. Shaffer 9 , Regina Girones Sarrio 10 , Sara Gunnestad Ribe 11 , Jane Wu 12 , Emmett Schmidt 13 , Peter Kubiak 12 , Chinyere Okpara 14 , Alan D. Smith 14 , Louise Young 15 , Robert J. Motzer 1
  1. Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
  2. MD Anderson Cancer Center, University of Texas, Houston, TX, United States of America
  3. Washington University School of Medicine, St. Louis, MO, United States of America
  4. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, United States of America
  5. Hospital Universitario La Paz, Madrid, Spain
  6. Winship Cancer Institute of Emory University, Atlanta, GA, United States of America
  7. Rocky Mountain Cancer Center, Denver, CO, United States of America
  8. Arizona Oncology Associates, Tucson, AZ, United States of America
  9. New York Oncology Hematology, Albany, NY, United States of America
  10. Hospital Universitari i Politècnic La FE, Valencia, Spain
  11. Sorlandet Hospital Kristiansand, Kristiansand, Norway
  12. Eisai Inc., Woodcliff Lake, NJ, United States of America
  13. Merck & Co., Inc., Kenilworth, NJ, United States of America
  14. Eisai Ltd., Hatfield, United Kingdom
  15. Eisai Australia Pty Ltd, Melbourne, VIC, Australia


LEN + everolimus is approved for advanced RCC following VEGF-targeted therapy. PEMBRO + axitinib is approved first-line for advanced RCC. We report phase 2 results of the RCC cohort of a phase 1b/2 trial (Study 111/KEYNOTE-146) of LEN + PEMBRO in patients with mccRCC.


This multicenter, open-label study enrolled patients with mccRCC (measurable per irRECIST) who progressed previously per RECIST v1.1 (confirmed ≥ 4 weeks later) during or following ICI therapy. Patients received LEN 20 mg orally daily + PEMBRO 200 mg IV Q3W. Tumor assessments were performed every 6 weeks (until week 24), then every 9 weeks. The primary endpoint was objective response rate (ORR) at week 24 (irRECIST per investigator assessment).


104 patients were enrolled. Median duration of follow-up for OS was 12.3 months. 65% of patients had prior anti-PD-1/PD-L1 and anti-VEGF therapy in combination or sequentially; 37% of patients had prior nivolumab + ipilimumab. At week 24, 53/104 patients achieved a confirmed partial response; ORR was 51% (Table). Data by independent imaging review (RECIST v1.1) and subgroup analyses will also be available. The most common treatment-related adverse events (TRAEs) were fatigue (53%), diarrhea (46%), and proteinuria (39%). Two grade 5 TRAEs occurred (upper gastrointestinal hemorrhage; sudden death). 15% of patients discontinued treatment due to TRAEs.


LEN + PEMBRO demonstrated promising antitumor activity in mccRCC after ICI therapy. No new safety signals were detected.

 Efficacy by investigator assessment



 ORR, n/N (%) [95% CI]

57/104 (54.8) [44.7-64.6]

  Prior anti-PD-1/PD-L1 and anti-VEGF

40/68 (58.8) [46.2-70.6]

  Prior nivolumab + ipilimumab

18/38 (47.4) [31-64.2]

  PD-L1 status



22/44 (50) [34.6-65.4]


27/43 (62.8) [46.7-77]

 ORR(week 24), n (%) [95% CI]

53 (51) [41-60.9]

 DORa (95% CI)

12.2 (8.5-18.2)

 Time to responsea (range)

1.6 (1.2-13.7)

 PFSa (95% CI)

11.7 (9.4-17.7)


Not reached

 aMedian, months