Phase II study of lenvatinib plus pembrolizumab for patients with immunotherapy-naive advanced gastric cancer following first-line therapy
6 affiliations
- 1Department of Medical Oncology, Stanford University School of Medicine, Stanford, USA
- 2Division of Medical Oncology, NYU Laura and Isaac Pearlmutter Cancer Center, New York, USA
- 3Division of Biostatistics, Department of Population Health, NYU Grossman School of Medicine and Biostatistics Shared Resource, Pearlmutter Cancer Center, New York, USA
- 4Department of Biostatistics, NYU College of Global Public Health, New York, USA
- 5New York-Presbyterian Weill Cornell Medical Center, New York, USA
- 6Division of Hematology and Oncology, Mount Sinai Tisch Cancer Center, New York, USA
Abstract
Background: Treatment options for refractory gastric cancer are limited. Preclinical data suggest interplay between angiogenesis and immune regulation, with vascular endothelial growth factor impairing antitumor immunity through decreasing antigen presentation, effector function, and immune cell trafficking. This phase II study evaluated lenvatinib plus pembrolizumab in the refractory setting. Patients and methods: Eligible patients had advanced gastric or gastroesophageal junction adenocarcinoma with measurable disease, Eastern Cooperative Oncology Group ≤ 1, and progression after ≥1 prior therapy, without prior immune checkpoint inhibitor exposure. Patients received pembrolizumab 200 mg i.v. every 21 days and lenvatinib 20 mg orally daily, with a 7-day lead-in. Primary endpoint was objective response rate. Using Simon optimal two-stage design, 29 patients were planned; the study would be considered positive if ≥6 responses were observed. Secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS). Results: Enrollment was prematurely suspended at 24 patients due to evolving practice patterns. Median age was 63 years; 75% were male; 63% were White. Seven patients (29%) received ≥2 lines of therapy. Among 20 assessable patients, 5 (25%) achieved partial responses, including 2 with combined positive score (CPS) <1 tumors. Median duration of response was 31.6 weeks. Median PFS and OS were 12.9 and 21.4 weeks, respectively. Treatment was well tolerated with no new safety signals. Conclusions: Lenvatinib plus pembrolizumab did not meet the predefined efficacy threshold in the overall cohort. However, treatment was well tolerated and encouraging responses were seen in patients with CPS <1 tumors. Although the sample size was limited, these findings suggest that further investigation of this treatment strategy in patients with CPS < 1 disease may be warranted.
Related
- Treatment-Free Interval as a Prognostic Factor for Survival Outcomes in Patients with Advanced or Recurrent Endometrial Cancer Treated with Pembrolizumab Plus Lenvatinib: A Multi-Institutional Real-World Cohort Study
- Lenvatinib starting doses below 20 mg versus 20 mg with pembrolizumab in advanced or recurrent endometrial cancer: a systematic review and meta-analysis of comparative observational evidence
- Pembrolizumab plus lenvatinib in the treatment of unresectable cutaneous angiosarcoma: a study protocol of multicentre, open-label phase II study (NCCH2213, PLAS)
- 535 BC3195, a novel cadherin-3 targeting antibody drug conjugate, combined with pembrolizumab in patients with advanced solid malignancies: preliminary results from a phase I/II study (BC3195-103/G36)
- Lenvatinib plus pembrolizumab in pretreated metastatic B3 thymoma and thymic carcinoma (PECATI): a single-arm, phase 2 trial
BibTeX
@article{lee2026phase,
title = {{Phase II study of lenvatinib plus pembrolizumab for patients with immunotherapy-naive advanced gastric cancer following first-line therapy}},
author = {J.W. Lee and P.E. Oberstein and J.D. Goldberg and M. Jia and D. Becker and D. Siolas and N. Beri and T. Ryan and P. Kozuch and B. Levinson and L.P. Leichman and D.J. Cohen},
journal = {ESMO Gastrointestinal Oncology},
year = {2026},
month = oct,
doi = {10.1016/j.esmogo.2026.100420},
url = {https://doi.org/10.1016/j.esmogo.2026.100420},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Phase II study of lenvatinib plus pembrolizumab for patients with immunotherapy-naive advanced gastric cancer following first-line therapy
AU - J.W. Lee
AU - P.E. Oberstein
AU - J.D. Goldberg
AU - M. Jia
AU - D. Becker
AU - D. Siolas
AU - N. Beri
AU - T. Ryan
AU - P. Kozuch
AU - B. Levinson
AU - L.P. Leichman
AU - D.J. Cohen
PY - 2026
DA - 2026/10/21
JO - ESMO Gastrointestinal Oncology
DO - 10.1016/j.esmogo.2026.100420
UR - https://doi.org/10.1016/j.esmogo.2026.100420
AB - Background: Treatment options for refractory gastric cancer are limited. Preclinical data suggest interplay between angiogenesis and immune regulation, with vascular endothelial growth factor impairing antitumor immunity through decreasing antigen presentation, effector function, and immune cell trafficking. This phase II study evaluated lenvatinib plus pembrolizumab in the refractory setting. Patients and methods: Eligible patients had advanced gastric or gastroesophageal junction adenocarcinoma with measurable disease, Eastern Cooperative Oncology Group ≤ 1, and progression after ≥1 prior therapy, without prior immune checkpoint inhibitor exposure. Patients received pembrolizumab 200 mg i.v. every 21 days and lenvatinib 20 mg orally daily, with a 7-day lead-in. Primary endpoint was objective response rate. Using Simon optimal two-stage design, 29 patients were planned; the study would be considered positive if ≥6 responses were observed. Secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS). Results: Enrollment was prematurely suspended at 24 patients due to evolving practice patterns. Median age was 63 years; 75% were male; 63% were White. Seven patients (29%) received ≥2 lines of therapy. Among 20 assessable patients, 5 (25%) achieved partial responses, including 2 with combined positive score (CPS) <1 tumors. Median duration of response was 31.6 weeks. Median PFS and OS were 12.9 and 21.4 weeks, respectively. Treatment was well tolerated with no new safety signals. Conclusions: Lenvatinib plus pembrolizumab did not meet the predefined efficacy threshold in the overall cohort. However, treatment was well tolerated and encouraging responses were seen in patients with CPS <1 tumors. Although the sample size was limited, these findings suggest that further investigation of this treatment strategy in patients with CPS < 1 disease may be warranted.
SN - 2949-8198
ER -