The first report of patients with solid tumors treated with LP-118, a novel Bcl-2/Bcl-xL dual inhibitor
Presenter: Qing Zhou Session: Phase I Clinical Trials Time: 4/21/2026 9:00:00 AM → 4/21/2026 12:00:00 PM
Authors
Qing Zhou 1 , Xiaorong Dong 2 , Jianya Zhou 3 , Duidui Hong 4 , Yue Shen 4 , Fenlai Tan 4 , Xiang Xiao 4 , Yejiang Lou 4 , Jiemin Xie 4 , Yilong Wu 1 1 Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China, 2 Cancer Center, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, China, 3 Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, 4 Guangzhou Lupeng Pharmaceutical Co., Ltd., Guangzhou, China
Abstract
Background: Bcl-2 family proteins are often overexpressed in tumors, which blocks apoptosis and promotes uncontrolled cell proliferation. Navitoclax has shown anti-tumor activity in various malignancies but induces dose-limiting thrombocytopenia due to Bcl-xL inhibition. LP-118 is a novel Bcl-2/Bcl-xL inhibitor with potent activity against Bcl-2 and fine-tuned activity against Bcl-xL, designed to minimize platelet toxicity while maintaining robust anti-tumor activity. Methods: This is an open-label, phase I study of LP-118 in patients with solid tumors or hematological malignancies (NCT05025358). Eligible subjects had failed standard therapies and had measurable disease. LP-118 was administrated orally, with doses ranging from 50 to 700 mg/day using the 3+3 design. The study endpoints included safety, pharmacokinetic (PK) and preliminary efficacy. Here, we report results from the solid tumor cohort. Results: As of July 09, 2025, a total of 52 patients with solid tumors, including 42 with small cell lung cancer (SCLC) were enrolled. Baseline characteristics of the SCLC cohort are summarized in Table 1. Patients received LP-118 across 10 dose levels. PK analysis showed that LP-118 exposure increases with doses from 50-500 mg, then appears to plateau at 600-700 mg. Following once-daily (QD) administration of 500 mg, the mean C max,ss was 420.5 ng/mL, with AUCτ of 5138.1 ng·h/mL and the mean half-life was 7.9 hours, supporting QD dosing. No dose-limiting toxicity (DLT) was reported, and the maximum tolerated dose (MTD) has not yet been reached. Common treatment related adverse events included leukopenia (53.8%), neutropenia (48.1%), lymphopenia (32.7%), blood creatine phosphokinase MB increased (30.8%), decreased appetite (30.8%), and anemia (30.8%), most of which were grade 1-2. Notably, the incidence of thrombocytopenia was 15.4%, with 4 subjects (7.7%) experienced grade 3 - 4 events. Of 32 efficacy-evaluable SCLC subjects treated at ≥300 mg QD, partial response was observed in 5 subjects and stable disease in 18 subjects, including one subject remaining on treatment for over 22 months. The objective response rate (ORR) was 15.6%, and the disease control rate (DCR) was 71.9%. The median overall survival (OS) was 8.15 months. Conclusion: LP-118 is a novel Bcl-2/Bcl-xL dual inhibitor with favorable safety and PK profiles. Preliminary efficacy observed in patients with SCLC is encouraging, supporting further clinical evaluations. Table 1. Baseline characteristics of SCLC patients (N=42) Median age (range), years 62.5 (39-77) Male, n (%) 37 (88.1) ECOG performance status, n (%) 0 5 (11.9) 1 37 (88.1) Disease stage, n (%) III 3 (7.1) IV 39 (92.9) Median line of prior therapies (range) 2 (1-6) No. of prior therapies, n (%) 1 18 (42.9) 2 15 (35.7) ≥3 9 (21.4) Prior therapeutic regimens, n (%) Chemotherapy 42 (100) Immunotherapy 38 (90.5) Targeted therapy 9 (21.4)
Disclosure
Q. Zhou, None.. X. Dong, None.. J. Zhou, None.. D. Hong, None.. Y. Shen, None.. F. Tan, None.. X. Xiao, None.. Y. Lou, None.. J. Xie, None.. Y. Wu, None.
Cited in
Control: 9636 · Presentation Id: 12098 · Meeting 21436