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ASH Joint Program Committees have selected two LP-168 clinical abstracts in NHL and MCL for poster presentations at the 65th ASH Annual Meeting and Exposition, December 9-12, 2023, in San Diego, California. LP-168 is a novel next generation BTK inhibitor invented by Guangzhou Lupeng Pharmaceutical Co., Ltd.. Abstracts are available on the ASH website.

LP-168 clinical presentation details (by presentation time)

【Title】Safety and Efficacy Results from the Phase I Study of a Novel Dual Covalent and Non-Covalent Next Generation Inhibitor of Bruton’s Tyrosine Kinase LP-168 in Patients with Relapsed/Refractory Mantle Cell Lymphoma

【Publication Number】3033

【Session】623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II

【Time & Location】Sunday, December 10, 2023: 6:00 PM-8:00 PM, Halls G-H (San Diego Convention Center)

【Presenter】Dr. Yuqin Song

【Abstract highlight】

Methods: This is a Phase 1 first-in-human multi-center open-label study of LP-168 enrolling Chinese patients with B cell Non-Hodgkin Lymphoma (NHL) who have progressed after at least 1 or 2 prior treatments. The study has two parts: Phase 1a: "3+3" dose escalation and Phase 1b: dose expansion in disease-specific cohorts (e.g. R/R MCL, R/R MZL, etc.).

Results: By 31 May 2023, 33 R/R MCL patients who received at least one dose were enrolled and received LP-168 100 mg (n=8), 150 mg (n=24), and 200 mg (n=1) QD, respectively. Median lines of prior therapies were 2 (range, 1-11) with 24.2% refractory to the last prior treatment. All patients have received rituximab or a rituximab-containing regimen. 19 (57.6%) subjects have received at least a cBTKi or cBTKi-containing regimen.

The most common treatment emergent adverse events (TEAEs) were platelet count decreased (30.3%), neutropenia and anemia (27.3% each) and COVID-19 (24.2%), most of which were Grade 1. Serious AE (SAE) occurred in 3 (9.1%) subjects. Dose interruptions due to AE occurred in 7 patients (21.2%)，but no AE has led to dose adjustment, drug discontinuation or death.

Of 31 efficacy evaluable subjects, 24 (77.4%) achieved response including 12 (38.7%) complete metabolic response or complete response (CMR/CR). More importantly, of 17 subjects who had prior cBTKi exposure, 12 (70.6%) responded to LP-168 and 6 (35.3%) achieved CMR. LP-168 also showed efficacy in 2 subjects who have received ≥ 2 cBTKi treatments.

Conclusion: In this Phase 1 trial, the novel BTK inhibitor LP-168 demonstrated a high CR rate and durable response in heavily pre-treated R/R MCL with favorable safety profile. Moreover, LP-168 could effectively overcome the acquired resistance to prior cBTKi. Based on the safety, PK and preliminary efficacy data from the Phase 1 study so far, we have determined the recommended phase 2 dose (RP2D) for MCL as 150 mg QD. A phase 2 trial of LP-168 in R/R MCL is currently ongoing (NCT05716087).

【ASH website link】

https://ash.confex.com/ash/2023/webprogram/Paper180694.html

【Title】A Novel Dual Covalent and Non-Covalent Next Generation Inhibitor of Bruton’s Tyrosine Kinase LP-168 in Patients with Relapsed/Refractory B Cell Non-Hodgkin Lymphoma: Safety and Efficacy Results from a Phase 1 Study

【Publication Number】4400

【Session】623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III

【Time & Location】Monday, December 11, 2023: 6:00 PM-8:00 PM, Halls G-H (San Diego Convention Center)

【Presenter】Dr. Yuqin Song

【Abstract highlight】

Methods: This multi-center Phase 1 study contains a “3+3” dose escalation part (Phase 1a) followed by a dose expansion part (Phase 1b). Subjects with R/R B-NHL are eligible to receive LP-168 once daily treatment until disease progression or unacceptable toxicity.

Results: By 31 May 2023, 68 subjects (33 MCL, 14 diffuse large B cell lymphoma [DLBCL], 15 marginal zone lymphoma [MZL], 3 CLL/SLL, 2 follicular lymphoma [FL] and 1 primary mediastinal large B cell lymphoma [PMBCL]) were enrolled. Cohorts of 100 mg (N=13) 150 mg (N=40) and 200 mg (N=15) taken QD were treated respectively. The median number of prior therapies was 2 (range, 1-10) and 25 (36.8%) subjects had received at least a cBTKi-containing regimen. The median follow-up was 4.5 (0.3-21.3) months with 46 subjects remaining on treatment.

No dose-limiting toxicities (DLTs) were observed during dose escalation from 100mg QD, 150mg QD to 200mg QD, and the maximum tolerated dose (MTD) was not reached. The most common treatment-emergent adverse events (TEAEs) occurring in ≥20% subjects included neutropenia, platelet count decreased and anemia, most of which were Grade 1 or 2. Only 9 (13.2%) subjects experienced Serious Adverse Event (SAE). No major bleeding, hypertension, or atrial fibrillation was observed in this study. Dose reduction occurred in only 1 subject due to AE. No TEAE led to drug discontinuation.

Of 60 efficacy-evaluable subjects, overall response rate (ORR) was 65.0%. In particular, ORR in R/R MCL (N=31) was 77.4% with a CR of 38.7%, non-GCB DLBCL (N=10) had an ORR of 70.0% with a CR of 40.0% and MZL (N=11) had an ORR of 72.7% with a CR of 9.1%.

LP-168 steady state plasma exposure increases dose-dependently with limited accumulation at 100 to 200 mg. Plasma concentration peaks at approximately 2 to 3 hours at fasted state, the average terminal half-life was 15.1 hours, supporting once daily dosing.

Conclusion: The current results of the Phase 1 study showed that LP-168 was well tolerated at 100-200 mg QD with favorable PK profile and has demonstrated encouraging efficacy in multiple B-cell malignancies, including those who had progressed on prior cBTKi.

【ASH website link】

https://ash.confex.com/ash/2023/webprogram/Paper180485.html