Xin-Xin Cao, Qi Zhu, Zhen Cai, Jie Ma, Hui Zhou, Long Chang, Lai-Ping Zhong, Zhu-Li Wu, Xingli Wang, Pu Han, Hong-Mei Lin, Zhen Wei, Jia-Yan Guo, Yang Zheng, Jian Li
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This single-arm, multicentre, phase 2 study evaluated the efficacy and safety of the selective MEK1/2 inhibitor luvometinib in adult patients with histiocytic neoplasms.</p><p><strong>Methods: </strong>Patients (aged >16 years), regardless of tumour genotype and who were either treatment-naïve or relapse/refractory, were enrolled and received oral luvometinib, 8 mg, once daily in 28-day cycles until disease progression, death, unacceptable toxicity, withdrawal of consent, or end of the study. The primary end point was overall response rate (ORR) assessed by an independent review committee according to positron emission tomography response criteria. This trial was registered with chinadrugtrials.org.cn (CTR20221069) and chictr.org.cn (ChiCTR2300067955).</p><p><strong>Findings: </strong>Between June 27, 2022 and February 2, 2024, 30 patients were enrolled; they were followed up for a median duration of 16.2 months (range, 1.5-19.3). In 29 evaluable patients, 22 (75.9%) had Langerhans cell histiocytosis, 3 (10.3%) had Erdheim-Chester disease, and 4 (13.8%) had other subtypes. Most (86.2%) patients had previously received systemic therapy and 27.6% had received ≥3 lines. With a median follow-up of 16.2 months, the ORR was 82.8% (95% CI, 64.2-94.2), with a median time to response of 2.9 months (range, 2.6-6.0) and median duration of response not reached. The 12-month progression-free survival rate was 74.4% (95% CI, 49.8-88.2). Grade ≥3 treatment-emergent adverse events occurred in 13 (43.3%) patients, with folliculitis (10.0%), hypertriglyceridemia (10.0%), and blood creatine phosphokinase increased (6.7%) occurring in more than one patient. No treatment-emergent adverse events led to treatment discontinuation.</p><p><strong>Interpretation: </strong>Luvometinib demonstrated high and durable responses and a manageable safety profile in patients with histiocytic neoplasms.</p><p><strong>Funding: </strong>Shanghai Fosun Pharmaceutical Industrial Development Co., Ltd.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"88 ","pages":"103486"},"PeriodicalIF":10.0000,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481021/pdf/","citationCount":"0","resultStr":"{\"title\":\"Luvometinib in patients with Langerhans cell histiocytosis, Erdheim-Chester disease, and other histiocytic neoplasms: a single-arm, multicentre, phase 2 study.\",\"authors\":\"Xin-Xin Cao, Qi Zhu, Zhen Cai, Jie Ma, Hui Zhou, Long Chang, Lai-Ping Zhong, Zhu-Li Wu, Xingli Wang, Pu Han, Hong-Mei Lin, Zhen Wei, Jia-Yan Guo, Yang Zheng, Jian Li\",\"doi\":\"10.1016/j.eclinm.2025.103486\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Histiocytic neoplasms are a heterogeneous group of haematologic disorders marked by a high frequency of mutations in the somatic mitogen-activated protein kinase pathway. This single-arm, multicentre, phase 2 study evaluated the efficacy and safety of the selective MEK1/2 inhibitor luvometinib in adult patients with histiocytic neoplasms.</p><p><strong>Methods: </strong>Patients (aged >16 years), regardless of tumour genotype and who were either treatment-naïve or relapse/refractory, were enrolled and received oral luvometinib, 8 mg, once daily in 28-day cycles until disease progression, death, unacceptable toxicity, withdrawal of consent, or end of the study. The primary end point was overall response rate (ORR) assessed by an independent review committee according to positron emission tomography response criteria. This trial was registered with chinadrugtrials.org.cn (CTR20221069) and chictr.org.cn (ChiCTR2300067955).</p><p><strong>Findings: </strong>Between June 27, 2022 and February 2, 2024, 30 patients were enrolled; they were followed up for a median duration of 16.2 months (range, 1.5-19.3). In 29 evaluable patients, 22 (75.9%) had Langerhans cell histiocytosis, 3 (10.3%) had Erdheim-Chester disease, and 4 (13.8%) had other subtypes. Most (86.2%) patients had previously received systemic therapy and 27.6% had received ≥3 lines. With a median follow-up of 16.2 months, the ORR was 82.8% (95% CI, 64.2-94.2), with a median time to response of 2.9 months (range, 2.6-6.0) and median duration of response not reached. The 12-month progression-free survival rate was 74.4% (95% CI, 49.8-88.2). Grade ≥3 treatment-emergent adverse events occurred in 13 (43.3%) patients, with folliculitis (10.0%), hypertriglyceridemia (10.0%), and blood creatine phosphokinase increased (6.7%) occurring in more than one patient. 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Luvometinib in patients with Langerhans cell histiocytosis, Erdheim-Chester disease, and other histiocytic neoplasms: a single-arm, multicentre, phase 2 study.
Background: Histiocytic neoplasms are a heterogeneous group of haematologic disorders marked by a high frequency of mutations in the somatic mitogen-activated protein kinase pathway. This single-arm, multicentre, phase 2 study evaluated the efficacy and safety of the selective MEK1/2 inhibitor luvometinib in adult patients with histiocytic neoplasms.
Methods: Patients (aged >16 years), regardless of tumour genotype and who were either treatment-naïve or relapse/refractory, were enrolled and received oral luvometinib, 8 mg, once daily in 28-day cycles until disease progression, death, unacceptable toxicity, withdrawal of consent, or end of the study. The primary end point was overall response rate (ORR) assessed by an independent review committee according to positron emission tomography response criteria. This trial was registered with chinadrugtrials.org.cn (CTR20221069) and chictr.org.cn (ChiCTR2300067955).
Findings: Between June 27, 2022 and February 2, 2024, 30 patients were enrolled; they were followed up for a median duration of 16.2 months (range, 1.5-19.3). In 29 evaluable patients, 22 (75.9%) had Langerhans cell histiocytosis, 3 (10.3%) had Erdheim-Chester disease, and 4 (13.8%) had other subtypes. Most (86.2%) patients had previously received systemic therapy and 27.6% had received ≥3 lines. With a median follow-up of 16.2 months, the ORR was 82.8% (95% CI, 64.2-94.2), with a median time to response of 2.9 months (range, 2.6-6.0) and median duration of response not reached. The 12-month progression-free survival rate was 74.4% (95% CI, 49.8-88.2). Grade ≥3 treatment-emergent adverse events occurred in 13 (43.3%) patients, with folliculitis (10.0%), hypertriglyceridemia (10.0%), and blood creatine phosphokinase increased (6.7%) occurring in more than one patient. No treatment-emergent adverse events led to treatment discontinuation.
Interpretation: Luvometinib demonstrated high and durable responses and a manageable safety profile in patients with histiocytic neoplasms.
Funding: Shanghai Fosun Pharmaceutical Industrial Development Co., Ltd.
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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