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

doi:10.1002/cncr.70015

. 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 Rha¹, Eduardo Castanon², Sanjeev Gill³, Helene Senellart⁴, Juanita Lopez⁵, Iván Márquez-Rodas⁶, Iván Victoria⁷, Tae Min Kim⁸, Zarnie Lwin⁹, Michael C Burger¹⁰, Matteo Simonelli^{11

12}, Philippe A Cassier¹³, Andrew E Hendifar¹⁴, Paolo A Ascierto¹⁵, Corina Dutcus¹⁶, Chinyere E Okpara¹⁷, Razi Ghori¹⁸, Fan Jin¹⁸, Roman Groisberg¹⁸, Luis Villanueva¹⁹

Affiliations

¹ Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Songdang Institute for Cancer Research, Seoul, Republic of Korea.
² Department of Oncology, Clínica Universidad de Navarra, Madrid, Spain.
³ Medical Oncology Department, Alfred Hospital, Melbourne, Victoria, Australia.
⁴ Integrated Center for Oncology, Centre René Gauducheau, Saint Herblain, France.
⁵ Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, UK.
⁶ Hospital General Universitario Gregorio Marañon and Universidad Complutense, Madrid, Spain.
⁷ Department of Medical Oncology, IDIBAPS, Hospital Clínic, Barcelona, Spain.
⁸ Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
⁹ Royal Brisbane and Women's Hospital, University of Queensland, Herston, Queensland, Australia.
¹⁰ Goethe University Frankfurt, University Hospital, Dr. Senckenberg Institute of Neurooncology, Frankfurt, Germany.
¹¹ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
¹² Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy.
¹³ Département de Cancérologie Médicale, Centre Léon Bérard, Lyon, France.
¹⁴ Department of Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California, USA.
¹⁵ Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Naples, Italy.
¹⁶ Eisai Inc., Nutley, New Jersey, USA.
¹⁷ Eisai Ltd., Hatfield, UK.
¹⁸ Merck & Co., Inc., Rahway, USA.
¹⁹ Department of Oncology, Instituto Oncologico Fundacion Arturo Lopez Perez, Hospital Clinico Universidad de Chile, Santiago, Chile.

PMID: 40808295
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 et al. Cancer. 2025.

. 2025 Aug 15;131(16):e70015.

doi: 10.1002/cncr.70015.

Authors

Affiliations

¹ Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Songdang Institute for Cancer Research, Seoul, Republic of Korea.
² Department of Oncology, Clínica Universidad de Navarra, Madrid, Spain.
³ Medical Oncology Department, Alfred Hospital, Melbourne, Victoria, Australia.
⁴ Integrated Center for Oncology, Centre René Gauducheau, Saint Herblain, France.
⁵ Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, UK.
⁶ Hospital General Universitario Gregorio Marañon and Universidad Complutense, Madrid, Spain.
⁷ Department of Medical Oncology, IDIBAPS, Hospital Clínic, Barcelona, Spain.
⁸ Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
⁹ Royal Brisbane and Women's Hospital, University of Queensland, Herston, Queensland, Australia.
¹⁰ Goethe University Frankfurt, University Hospital, Dr. Senckenberg Institute of Neurooncology, Frankfurt, Germany.
¹¹ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
¹² Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy.
¹³ Département de Cancérologie Médicale, Centre Léon Bérard, Lyon, France.
¹⁴ Department of Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California, USA.
¹⁵ Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Naples, Italy.
¹⁶ Eisai Inc., Nutley, New Jersey, USA.
¹⁷ Eisai Ltd., Hatfield, UK.
¹⁸ Merck & Co., Inc., Rahway, USA.
¹⁹ Department of Oncology, Instituto Oncologico Fundacion Arturo Lopez Perez, Hospital Clinico Universidad de Chile, Santiago, Chile.

PMID: 40808295
DOI: 10.1002/cncr.70015

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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References

REFERENCES

1. Ostrom QT, Cioffi G, Gittleman H, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012‐2016. Neuro Oncol. 2019;21(suppl 5):v1‐v100. doi:10.1093/neuonc/noz150
1. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN guidelines). Central Nervous System Cancers Version 2.2022. Accessed January 25, 2023. https://www.nccn.org/guidelines/
1. Stupp R, Taillibert S, Kanner A, et al. Effect of tumor‐treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017;318(23):2306‐2316. doi:10.1001/jama.2017.18718
1. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987‐996. doi:10.1056/nejmoa043330
1. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5‐year analysis of the EORTC‐NCIC trial. Lancet Oncol. 2009;10(5):459‐466. doi:10.1016/s1470‐2045(09)70025‐7

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[1] Ostrom QT, Cioffi G, Gittleman H, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012‐2016. Neuro Oncol. 2019;21(suppl 5):v1‐v100. doi:10.1093/neuonc/noz150

[2] Ostrom QT, Cioffi G, Gittleman H, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012‐2016. Neuro Oncol. 2019;21(suppl 5):v1‐v100. doi:10.1093/neuonc/noz150

[3] National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN guidelines). Central Nervous System Cancers Version 2.2022. Accessed January 25, 2023. https://www.nccn.org/guidelines/

[4] National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN guidelines). Central Nervous System Cancers Version 2.2022. Accessed January 25, 2023. https://www.nccn.org/guidelines/

[5] Stupp R, Taillibert S, Kanner A, et al. Effect of tumor‐treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017;318(23):2306‐2316. doi:10.1001/jama.2017.18718

[6] Stupp R, Taillibert S, Kanner A, et al. Effect of tumor‐treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017;318(23):2306‐2316. doi:10.1001/jama.2017.18718

[7] Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987‐996. doi:10.1056/nejmoa043330

[8] Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987‐996. doi:10.1056/nejmoa043330

[9] Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5‐year analysis of the EORTC‐NCIC trial. Lancet Oncol. 2009;10(5):459‐466. doi:10.1016/s1470‐2045(09)70025‐7

[10] Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5‐year analysis of the EORTC‐NCIC trial. Lancet Oncol. 2009;10(5):459‐466. doi:10.1016/s1470‐2045(09)70025‐7

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

Affiliations

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

Authors

Affiliations

Abstract

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References

REFERENCES

Associated data

Grants and funding