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Clinical Trial
. 2025 Aug 15;131(16):e70015.
doi: 10.1002/cncr.70015.

Lenvatinib plus pembrolizumab for patients with previously treated select solid tumors: Results from the phase 2 LEAP-005 study recurrent glioblastoma cohort

Sun Young Rha  1 , Eduardo Castanon  2 , Sanjeev Gill  3 , Helene Senellart  4 , Juanita Lopez  5 , Iván Márquez-Rodas  6 , Iván Victoria  7 , Tae Min Kim  8 , Zarnie Lwin  9 , Michael C Burger  10 , Matteo Simonelli  11   12 , Philippe A Cassier  13 , Andrew E Hendifar  14 , Paolo A Ascierto  15 , Corina Dutcus  16 , Chinyere E Okpara  17 , Razi Ghori  18 , Fan Jin  18 , Roman Groisberg  18 , Luis Villanueva  19
Affiliations
Clinical Trial

Lenvatinib plus pembrolizumab for patients with previously treated select solid tumors: Results from the phase 2 LEAP-005 study recurrent glioblastoma cohort

Sun Young Rha et al. Cancer. .

Abstract

Background: Patients with recurrent glioblastoma (GBM) have a poor prognosis and limited treatment options. The authors report the efficacy and safety of lenvatinib plus pembrolizumab in participants with recurrent GBM enrolled in the phase 2, multicohort LEAP-005 study (NCT03797326).

Methods: Eligible participants had histologically confirmed GBM (World Health Organization grade IV) with disease progression since previous treatment, and one or more prior lines of therapy. Participants were enrolled regardless of tumor programmed cell death ligand 1 (PD-L1) status and received oral lenvatinib 20 mg per day plus intravenous pembrolizumab 200 mg every 3 weeks. The dual primary end points were objective response rate (ORR; per Response Assessment in Neuro-Oncology by blinded independent central review) and safety.

Results: A total of 101 participants were enrolled, with median (range) follow-up of 23.7 (16.4‒46.6) months. The median (range) duration of treatment with lenvatinib plus pembrolizumab was 3.4 (0.3‒32.2) months. The ORR (95% confidence interval [CI]) was 20% (13%‒29%), with 20 participants achieving a partial response, and the median (range) duration of response was 3.7 (1.4+ to 27.6) months. Median (95% CI) progression-free survival was 3.0 (2.7‒4.0) months and median (95% CI) overall survival was 8.6 (7.4‒10.8) months. Responses were observed regardless of PD-L1 status. Treatment-related adverse events occurred in 93 participants (92%; grade 3‒5, n = 41 [41%]). Two participants died due to treatment-related adverse events (intestinal perforation and pneumonitis).

Conclusions: The combination of lenvatinib plus pembrolizumab demonstrated antitumor activity in a small subpopulation of participants with recurrent GBM as second-line or later treatment. The safety profile was manageable.

Keywords: lenvatinib; pembrolizumab; phase 2; programmed cell death ligand 1; recurrent glioblastoma.

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Conflict of interest statement

Sun Young Rha reports research funding to institution for the present work from MSD; grant and/or contract funding to institution for clinical trials outside the present work from AstraZeneca, Ono Pharmaceutical, Eisai, Ipsen, MSD, Merck KGaA, Pfizer, BeiGene, Astellas Pharma, AMGEN, ALX Oncology, Zymeworks, Macrogenics, Seagen, Bold Therapeutics, MedPacto, ABLBIO, Daiichi Sankyo, Taiho Pharmaceutical, Leap Therapeutics, and Arcus Biosciences; consulting fees from LG Biochem and Indivumed; honoraria from MSD, Lilly, Daiichi‐Sankyo, Eisai, Ipsen, Amgen, Astellas, and Sanofi; and fees for participation on a data safety monitoring board or advisory board for Amgen, Toray, and Arcus. Eduardo Castanon reports consulting fees from Glaxo Smith Kline, Bristol‐Myers Squibb, Pfizer, and MSD; honoraria from Glaxo Smith Kline, Bristol‐Myers Squibb, and Pfizer; and fees for participation on an advisory board for MSD. Juanita Lopez reports grant and/or contract funding to institution from Roche‐Genentech, MSD, Astex, Janssen, and Verastem; and fees for participation on an advisory board for Roche‐Genentech, Glaxo Smith Kline, and Servier. Iván Márquez‐Rodas reports consulting fees from Amgen, Astra Zeneca, BiolineRx, Bristol‐Myers Squibb, Celgene, Glaxo Smith Kline, Highlight Therapeutics, Immunocore, Merck Serono, MSD, Novartis, Pierre Fabre, Regeneron, Roche, Sanofi, and Sun Pharma; and travel and/or meeting support from Amgen, Bristol‐Myers Squibb, Glaxo Smith Kline, Highlight Therapeutics, MSD, Novartis, Pierre Fabre, Roche, and Sun Pharma. Iván Victoria reports honoraria from MSD Oncology. Tae Min Kim reports research funding to institution from ABBVIE, Amgen, AstraZeneca/Medimmune, Bayer, Black Diamond Therapeutics, Blueprint Medicines, Boryung, Bristol‐Myers Squibb, Celgene, Dizal, EMD Serono Inc, Enliven Therapeutics, F. Hoffmann‐La Roche, Ltd/Genentech, Inc, Fore Biotherapeutics, Hanmi, Genmab, Janssen, MSD, Novartis, Pfizer, RAPT Therapeutics, Regeneron, Sanofi, Takeda, Taiho, and Yuhan; consulting fees from AstraZeneca, Daiichi‐Sankyo, HK inno.N, IMBDx, Inc, Janssen, Regeneron, Roche/Genentech, Samsung Bioepis, and Takeda; and fees for participation on a data safety monitoring board or advisory board for AstraZeneca, Janssen, Regeneron, Roche/Genentech, Samsung Bioepis, and Takeda. Zarnie Lwin Reports fees for participation on a data safety monitoring board or advisory board from MSD; and honoraria from MSD. Michael C. Burger reports research support for projects outside the present work from Boehringer Ingelheim; and fees for participation on an advisory board for Servier. Matteo Simonelli reports consulting fees from Glaxo Smith Kline; travel and/or meeting support from Pfizer, Sanofi, and Roche; and fees for participation on a data safety monitoring board or advisory board for Sanofi, Incyte, Glaxo Smith Kline, Servier, and Bristol‐Myers Squibb/Celgene. Philippe A. Cassier reports research funding for the present work from MSD; grants and/or contract funding to institution from AbbVie, ADCT, Adlai Nortye, Amgen, Bristol‐Myers Squibb, Boehringer Ingelheim, Blueprint, C4 Therapeutics, Debio Pharm, Dragonfly, Exelixis, Incyte, Iteos, Janssen, Kinnate, Lilly, Molecular Partners, MSD, Novartis, Ose Immunotherapeutics, Pierre Fabre, Relay, Roche/Genentech, Sotio, Taiho, Tango, Toray, Turningpoint, and Transgene; consulting fees from Boehringer Ingelheim, Ose Immunotherapeutics, and Scenic; travel and/or meeting support from Novartis; fees for participation on a data safety monitoring board or advisory board for BMS; and research equipment, materials, or other support to institution from Debio Pharm, Glaxo Smith Kline, MSD, and Novartis. Andrew E. Hendifar reports consulting fees from Pfizer and Ipsen; and fees for participation on a data safety monitoring board from Rayzebio. Paolo A. Ascierto reports grant and/or contract funding from Bristol‐Myers Squibb, Roche‐Genentech, Pfizer, and Sanofi; consulting fees from Bristol‐Myers Squibb, Roche‐Genentech, MSD, Novartis, Merck Serono, Pierre‐Fabre, Sun Pharma, Sanofi, Sandoz, Italfarmaco, Pfizer, Lunaphore, Medicenna, BioAI Health, ValoTx, Replimmune, Bayer, Philogen, BionTech, and Incyte; travel and/or meeting support from Pfizer, BioAI Health, Replimmune, MSD, Pierre Fabre, and Philogen; and fees for participation on a data safety monitoring board or advisory board for Bristol‐Myers Squibb, Roche‐Genentech, MSD, Novartis, Boehringer Ingelheim, Regeneron, Nouscom, Erasca, Anaveon, Genmab, and Menarini. Corina Dutcus is an employee of Eisai Inc., Nutley, NJ, USA. Chinyere E. Okpara is an employee of Eisai Ltd., Hatfield, UK. Razi Ghori is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Fan Jin is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and owns stock in Merck & Co., Inc., Rahway, NJ, USA. Roman Groisberg is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and owns stock in Merck & Co., Inc., Rahway, NJ, USA. Luis Villanueva reports research funding for the present work from MSD; and research funding from MSD and Bristol‐Myers Squibb. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Time on study treatment and response evaluation per RANO by central radiology assessment among participants with a confirmed objective response (i.e., confirmed CR or PR). One participant with confirmed best overall response of partial response is shown without symbol indicating partial response (second bar from top) because response assessment time point was missing as of data cutoff for this analysis. CR, complete response; PR, partial response; RANO, Response Assessment in Neuro‐Oncology.
FIGURE 2
FIGURE 2
Best percentage change from baseline in target lesion size per RANO by central radiology assessment for target lesions in participants with GBM with one or more postbaseline imaging assessments (n = 94). Participants with percentage changes from baseline >100% (n = 3) are presented as 100%. GBM, glioblastoma; RANO, Response Assessment in Neuro‐Oncology.
FIGURE 3
FIGURE 3
Response duration per RANO by central radiology assessment for target lesions in participants with GBM (A) among all participants and (B) by PD‐L1 status. Progression‐free survival per RANO by central radiology assessment for target lesions in participants with GBM (C) among all participants and (D) by PD‐L1 status. Overall survival in participants with GBM in the lenvatinib plus pembrolizumab group (E) among all participants and (F) by PD‐L1 status. aOne participant with a confirmed best overall response of partial response was excluded from analysis due to missing data for response assessment time point as of data cutoff for this analysis. CPS, combined positive score; GBM, glioblastoma; PD‐L1, programmed cell death ligand 1; RANO, Response Assessment in Neuro‐Oncology.
See this image and copyright information in PMC

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