833O - A phase Ib study result of HMPL-689, a PI3Kδ inhibitor, in Chinese patients with relapsed/refractory lymphoma

Background

HMPL-689, a novel class I PI3Kδ inhibitor, has shown tolerable safety profile and encouraging preliminary efficacy in patients (pts) with relapsed/refractory (R/R) lymphoma in the dose-escalation stage of a phase I study (NCT03128164) in China (Junning C, et al, ASH 2020). Here we present the preliminary safety and efficacy results of the study evaluating HMPL-689 at recommended phase 2 dose (RP2D) of 30mg QD as a monotherapy in pts with R/R lymphomas.

Methods

Eligible pts had measurable R/R lymphoma who failed an anti-CD20 antibody (monotherapy or in combination) or systemic therapy. Patients received single agent HMPL-689 30mg QD continuously in sequential 28-day treatment cycles until progression, unacceptable toxicity, or death. The primary efficacy endpoint is investigator assessed objective response rate (ORR) using the International Working Group criteria (2008) and Lugano response criteria.

Results

As of March 30, 2021, a total of 75 pts had received at least one dose of HMPL-689 at RP2D, including 2 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/ SLL), 21 follicular lymphoma (FL), 14 marginal zone lymphoma (MZL), 7 mantle cell lymphoma (MCL) and 31 diffuse large B-cell lymphoma (DLBCL). The median age was 56 years (range 18 - 86 yrs). The median number of prior therapies was 2 (range 1- 8), and 41.3% of pts received ≥3 lines of therapy. The median follow up of all pts was 4.0 months (95% CI, 3.7- 5.5). Among the 60 pts who had at least one post-baseline tumor assessment, 8 pts achieved a complete response (CR), including 7 FL and 1 MCL and 23 partial responses. The ORR was 51.7% (31/60), the median time to response (TTR) was 1.9 months (95%CI, 1.8-1.9). Patients with FL demonstrated the ORR of 77.8% (14/18) and CR rate of 38.9% (7/18). The most common (≥ 10%) treatment emergent adverse events (TEAEs) were neutropenia, ALT increased, leukopenia, AST increased, hypertriglyceridemia, pneumonia and upper respiratory tract infection. The most common TEAEs of Grade ≥3 (≥10%) were neutropenia, pneumonia and rash.

Conclusions

HMPL-689 showed tolerable safety profile and promising single-agent clinical activity in pts with R/R B-cell lymphoma, with high ORR and CR rates noted particularly for FL patients.

Clinical trial identification

NCT03128164.

Editorial acknowledgement

Legal entity responsible for the study

Hutchison MediPharma Limited.

Funding

Hutchison MediPharma Limited.

Disclosure

X. Duan, S. Fan, Y. Cai, W. Su: Financial Interests, Institutional, Sponsor/Funding Hutchison Medi. Pharma. All other authors have declared no conflicts of interest.