Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

Lenvatinib + pembrolizumab in patients with renal cell carcinoma: updated results (#367)

Chung-Han Lee 1 , Vicky Makker 2 , Drew Rasco 3 , Mathew Taylor 4 , Daniel E Stepan 5 , Robert Shumaker 5 , Emmett V Schmidt 6 , Matthew Guo 5 , Corina Dutcus 5 , Louise Young 7 , Robert Motzer 2
  1. Memorial Sloan-Ketting Cancer Center, New York, USA
  2. Memorial Sloan Ketting Cancer Center, New York, USA
  3. START, San Antonio, Texas, USA
  4. Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, United States of America
  5. Eisai Inc., Woodcliff Lake, New Jersey, United States of America
  6. Merck Co. Inc, Kenilworth, New Jersey, USA
  7. Eisai Australia Pty Ltd, Melbourne, VIC, Australia

Aims: Lenvatinib, a multikinase inhibitor of VEGFR and other targets, is approved in combination with everolimus for advanced renal cell carcinoma (RCC) after 1 prior VEGF-targeted therapy.

Methods: In this multicenter, open-label, phase 1b/2 study (NCT02501096), patients with metastatic clear cell RCC and measurable disease per immune-related RECIST (irRECIST) received oral lenvatinib 20 mg/day + pembrolizumab 200 mg Q3W, IV. Tumor assessments were by study investigators using irRECIST, with retrospective independent radiographic review (IRR) per irRECIST and RECIST v1.1. The phase 2 primary endpoint was objective response rate at 24 weeks (ORRWK24).

Results: 30 Patients were enrolled: 12 (40%) had 0 and 18 (60%) had ≥1 prior anticancer therapy; 16 (53%) received ≥1 prior VEGF-targeted therapy. At data cutoff (August 1, 2017), median follow-up for progression-free survival (PFS) was 13.8 months (95% CI, 11.9–15.7). ORRWK24 (per investigator, irRECIST) was 63.3% (95% CI, 43.9–80.1). ORR (per IRR, RECIST v1.1) was 66.7% (95% CI, 47.2–82.7); median PFS was 17.7 months (95% CI, 9.6–NE). Efficacy outcomes are below (Table). Grade 3/4 adverse events (AEs) occurred in 21 (70%) patients; 4 (13%) discontinued treatment due to AEs. The most common AEs were diarrhea (83%), fatigue (70%), hypothyroidism (67%), stomatitis (63%), and nausea (60%).

Conclusions: Lenvatinib+pembrolizumab showed promising antitumor activity with manageable AEs, and no new safety signals were identified. A phase 3 study of lenvatinib+pembrolizumab and lenvatinib+everolimus versus sunitinib for the first-line treatment of advanced RCC is underway (NCT02811861).

Outcome

N=30

IRR

Investigator review

RECIST v1.1

irRECIST

irRECIST

ORR*, n (%)

   95% CI

20 (66.7)

47.2–82.7

20 (66.7)

47.2–82.7

21 (70.0)

50.6–85.3

Median duration of response, months

   95% CI

16.3

8.9–NE

NE

14.9–NE

18.4

10.3–NE

Median PFS, months

   95% CI

17.7

9.6–NE

17.7

10.2–NE

19.8

11.6–NE

*Overall ORR.

NE, not estimable.