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Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma with Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination

Arance, Ana ; De La Cruz-Merino, Luis ; Petrella, Teresa M. ; Jamal, Rahima ; Ny, Lars ; Carneiro, Ana LU orcid ; Berrocal, Alfonso ; Márquez-Rodas, Ivan ; Spreafico, Anna and Atkinson, Victoria , et al. (2023) In Journal of Clinical Oncology 41(1). p.75-85
Abstract

PURPOSE Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136).METHODSEligible patients with unresectable stage III-IV melanoma with confirmed progressive disease (PD) within 12 weeks of the last dose of a PD-1/L1 inhibitor given alone or with other therapies, including cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4) inhibitors, received lenvatinib 20 mg orally once daily plus ≤ 35 doses of pembrolizumab 200 mg intravenously once every 3... (More)

PURPOSE Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136).METHODSEligible patients with unresectable stage III-IV melanoma with confirmed progressive disease (PD) within 12 weeks of the last dose of a PD-1/L1 inhibitor given alone or with other therapies, including cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4) inhibitors, received lenvatinib 20 mg orally once daily plus ≤ 35 doses of pembrolizumab 200 mg intravenously once every 3 weeks until PD or unacceptable toxicity. The primary end point was objective response rate (ORR) per RECIST, version 1.1, by independent central review.RESULTSA total of 103 patients were enrolled and treated. The median study follow-up was 15.3 months. ORR in the total population was 21.4% (95% CI, 13.9 to 30.5), with three (2.9%) complete responses and 19 (18.4%) partial responses. The median duration of response was 8.3 months (range, 3.2-15.9+). ORR was 33.3% in the 30 patients with PD on prior anti-PD-1 plus anti-CTLA-4 therapy. The median progression-free survival and overall survival in the total population were 4.2 months (95% CI, 3.8 to 7.1) and 14.0 months (95% CI, 10.8 to not reached), respectively. Grade 3-5 treatment-related adverse events occurred in 47 (45.6%) patients, most commonly hypertension (21.4%); one patient died from a treatment-related event (decreased platelet count).CONCLUSIONLenvatinib plus pembrolizumab provides clinically meaningful, durable responses in patients with advanced melanoma with confirmed PD on prior PD-1/L1 inhibitor-based therapy, including those with PD on anti-PD-1 plus anti-CTLA-4 therapy. The safety profile was as expected. These data support lenvatinib plus pembrolizumab as a potential regimen for this population of high unmet need.

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type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Oncology
volume
41
issue
1
pages
11 pages
publisher
American Society of Clinical Oncology
external identifiers
  • pmid:35867951
  • scopus:85141668161
ISSN
0732-183X
DOI
10.1200/JCO.22.00221
language
English
LU publication?
yes
id
4f9f631a-b120-4533-90c7-97c9fa91c736
date added to LUP
2024-01-12 10:40:51
date last changed
2024-04-13 04:54:06
@article{4f9f631a-b120-4533-90c7-97c9fa91c736,
  abstract     = {{<p>PURPOSE Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136).METHODSEligible patients with unresectable stage III-IV melanoma with confirmed progressive disease (PD) within 12 weeks of the last dose of a PD-1/L1 inhibitor given alone or with other therapies, including cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4) inhibitors, received lenvatinib 20 mg orally once daily plus ≤ 35 doses of pembrolizumab 200 mg intravenously once every 3 weeks until PD or unacceptable toxicity. The primary end point was objective response rate (ORR) per RECIST, version 1.1, by independent central review.RESULTSA total of 103 patients were enrolled and treated. The median study follow-up was 15.3 months. ORR in the total population was 21.4% (95% CI, 13.9 to 30.5), with three (2.9%) complete responses and 19 (18.4%) partial responses. The median duration of response was 8.3 months (range, 3.2-15.9+). ORR was 33.3% in the 30 patients with PD on prior anti-PD-1 plus anti-CTLA-4 therapy. The median progression-free survival and overall survival in the total population were 4.2 months (95% CI, 3.8 to 7.1) and 14.0 months (95% CI, 10.8 to not reached), respectively. Grade 3-5 treatment-related adverse events occurred in 47 (45.6%) patients, most commonly hypertension (21.4%); one patient died from a treatment-related event (decreased platelet count).CONCLUSIONLenvatinib plus pembrolizumab provides clinically meaningful, durable responses in patients with advanced melanoma with confirmed PD on prior PD-1/L1 inhibitor-based therapy, including those with PD on anti-PD-1 plus anti-CTLA-4 therapy. The safety profile was as expected. These data support lenvatinib plus pembrolizumab as a potential regimen for this population of high unmet need.</p>}},
  author       = {{Arance, Ana and De La Cruz-Merino, Luis and Petrella, Teresa M. and Jamal, Rahima and Ny, Lars and Carneiro, Ana and Berrocal, Alfonso and Márquez-Rodas, Ivan and Spreafico, Anna and Atkinson, Victoria and Costa Svedman, Fernanda and Mant, Andrew and Khattak, Muhammad A. and Mihalcioiu, Catalin and Jang, Sekwon and Cowey, C. Lance and Smith, Alan D. and Hawk, Natalyn and Chen, Ke and Diede, Scott J. and Krepler, Clemens and Long, Georgina V.}},
  issn         = {{0732-183X}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  pages        = {{75--85}},
  publisher    = {{American Society of Clinical Oncology}},
  series       = {{Journal of Clinical Oncology}},
  title        = {{Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma with Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination}},
  url          = {{http://dx.doi.org/10.1200/JCO.22.00221}},
  doi          = {{10.1200/JCO.22.00221}},
  volume       = {{41}},
  year         = {{2023}},
}