Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, adult, Lymphomas, Clinical Research, B Cell lymphoma, Diseases, Lymphoid Malignancies, Study Population, Human
Methods: This multicenter 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. This study was designed to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of LP-168. The efficacy assessment was based on Lugano 2014, 2018 International Workshop on CLL (iwCLL) and the 6th International Workshop for WM response criteria.
Results: Between 10 August 2021 and 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 age was 59.2 (range, 32-79) years old; 22 (64.7%) were male. 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 (as detailed in Table 1). ≥Grade 3 treatment related adverse events (TRAEs, including possibly related, probably related and definitely related) included neutropenia (7.4%), lung infection (2.9%), lymphopenia, leukocytosis, lymphocytosis and oral cavity infection (1.5% each). 9 (13.2%) subjects experienced Serious Adverse Event (SAE). Serious adverse reactions included lung infection, oral cavity infection and lymphocytosis. No major bleeding, hypertension, or atrial fibrillation was observed in this study. Dose reduction occurred in only 1 subject due to AE (immune-mediated pancreatitis, unlikely related). No TEAE led to drug discontinuation. 1 subject experienced Grade 5 lung infection (not related to LP-168). 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% (Figure 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.
Disclosures: Shen: Guangzhou Lupeng Pharmaceutical Co: Current Employment. Chen: Newave Pharmaceutical Inc: Current Employment, Current holder of stock options in a privately-held company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Newave Pharmaceutical Inc.