Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

LEAP-004: updated data for lenvatinib plus pembrolizumab in patients with advanced melanoma and confirmed progressive disease on a prior PD-(L)1 inhibitor (#20)

Georgina V Long 1 , Luis de la Cruz-Merino 2 , Teresa M Petrella 3 , Rahima Jamal 4 , Lars Ny 5 , Ana Carneiro 6 , Alfonso Berrocal 7 , Ivan Márquez Rodas 8 , Anna Spreafico 9 , Victoria Atkinson 10 , Fernanda Costa Svedman 11 , Andrew Mant 12 , Alan D Smith 13 , Ke Chen 14 , Scott Diede 14 , Clemens Krepler 14 , Ana Arance 15
  1. Melanoma Institute Australia, University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, Australia
  2. Hospital Universitario Virgen Macarena, Seville, Spain
  3. Sunnybrook Health Sciences Centre, Toronto, Canada
  4. Centre hospitalier de l’Université de Montréal, Montréal, Canada
  5. University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
  6. Skåne University Hospital and Lund University, Lund, Sweden
  7. Hospital General Universitario de Valencia, Valencia, Spain
  8. Hospital General Universitario Gregorio Marañón and CIBERONC, Madrid, Spain
  9. Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada
  10. Princess Alexandra Hospital, University of Queensland, Brisbane, Australia
  11. Karolinska University Hospital, Stockholm, Sweden
  12. Eastern Health, Monash University, Melbourne, Australia
  13. Eisai Ltd., Hatfield, United Kingdom
  14. Merck & Co., Inc., Kenilworth, New Jersey, United States
  15. Hospital Clinic Barcelona, Barcelona, Spain

Aims: Initial findings of the phase 2 LEAP-004 study (NCT03776136) showed lenvatinib plus pembrolizumab had promising efficacy and manageable safety in patients with unresectable stage III-IV melanoma that progressed on a PD-(L)1 inhibitor. We present updated and expanded data.

Methods: Patients with iRECIST-confirmed PD within 12wk of receiving anti–PD-(L)1 therapy alone or in combination for ≥2 doses received lenvatinib 20mg/d QD plus ≤35 doses of pembrolizumab 200mg Q3W. Primary endpoint is ORR (RECIST v1.1 by BICR).

Results: 103 patients were enrolled. 68.0% had stage M1c/M1d disease, 55.3% had LDH>ULN (20.4% ≥2×ULN), and 58.3% received ≥2 prior treatments. With median study follow-up of 15.3mo (range 12.1-19.0), ORR remained 21.4% (95% CI 13.9-30.5) but CRs increased from 2 to 3. DCR was 66.0%. In subgroups, ORR was 33.3% in patients with prior anti–PD-1 plus anti–CTLA-4 (n=30), 18.2% in those with anti–PD-(L)1 as adjuvant only (n=11), and 22.6% in patients with primary resistance (best response of SD or PD to prior anti–PD-(L)1, n=62) and 22.7% in those with secondary resistance (PD following best response of CR or PR to prior anti–PD-(L)1, n=22) in the advanced setting. For the total population, median DOR increased to 8.3mo with a 38.6% estimated DOR at ≥9mo. Median (95% CI) PFS and OS were 4.2mo (3.8-7.1) and 14.0mo (10.8-NR), and 12-mo estimates were 18.5% and 54.5%. Treatment-related AE incidences were 45.6% for grade 3-4, 1.0% for grade 5, and 7.8% leading to discontinuation of lenvatinib and/or pembrolizumab.

Conclusions: Lenvatinib plus pembrolizumab shows clinically meaningful, durable responses and manageable safety in patients with advanced melanoma with confirmed PD on a PD-(L)1 inhibitor, including on anti–PD-1 plus anti–CTLA-4 therapy, and regardless of primary or secondary resistance. These data support lenvatinib plus pembrolizumab as a potential treatment for this high-unmet-need population.