Abstract 4403
Background
The B-cell receptor (BCR) signaling pathway plays a central role in non-Hodgkin lymphoma (NHL). Despite available agents targeting the BCR pathway, there continues to be a need for alternative therapies in the relapsed/refractory (R/R) setting due to agent-specific toxicities and differences in efficacy among agents and lymphoma subtypes. HMPL-689 is a highly selective small molecule inhibitor of phosphoinositide 3-kinase-delta (PI3Kδ), one of the key signaling molecules in BCR function. HMPL-689 has shown strong dose- and time-dependent inhibition of B-cell activation in rats. There is one ongoing clinical study in China, as well as the current study, which is being conducted in the United States (US) and European Union (EU). We present here a trial-in-progress description of this US/EU study, a phase 1 trial with a dose-escalation stage (ESC) and a dose expansion stage (EXP).
Trial design
Study Population: The target population is patients (pts) with histologically confirmed R/R NHL, including chronic lymphocytic leukemia, small lymphocytic lymphoma, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, or Waldenström’s macroglobulinemia/ lymphoplasmacytic lymphoma. In the ESC, patients must have exhausted all available approved therapy options. In the EXP, patients must be naïve to PI3K inhibitors. Objectives: The primary objective is to assess the safety and tolerability of HMPL-689 in pts with R/R NHL and to determine the maximum-tolerated dose (MTD) and the recommended phase 2 dose (RP2D). Preliminary efficacy will be evaluated in the dose expansion stage. Study Design: Dose-escalation will follow a modified toxicity probability interval scheme-2 and enroll 6 to 30 pts, until the MTD or the maximum sample size is reached. The proposed doses are 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, and 50 mg oral, once daily in 28-day cycles. HMPL-689 will be administered until disease progression, intolerable toxicity, no further benefit from study treatment, withdrawal, end of study, or death. The EXP will further evaluate the MTD/RP2D in ∼50 pts, with ∼10 pts each, in subtype-specific cohorts.
Clinical trial identification
NCT03786926.
Editorial acknowledgement
Hoang-Lan Nguyen, PhD, Hutchison MediPharma (US), Inc.
Legal entity responsible for the study
Hutchison MediPharma, Limited.
Funding
Hutchison MediPharma, Limited.
Disclosure
J. Cohen: Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Janssen; Advisory / Consultancy: Kite/Gilead; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): LAM Therapeutics; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): LRF; Research grant / Funding (institution): ASH; Research grant / Funding (institution): UNUM; Research grant / Funding (institution): BioInvent; Research grant / Funding (institution): AstraZeneca. R. Cordoba Mascunano: Advisory / Consultancy, Travel / Accommodation / Expenses: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Gilead; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Speaker Bureau / Expert testimony: Bristol-Myers Squibb. A.J.M. Ferreri: Advisory / Consultancy, Travel / Accommodation / Expenses: Gilead; Advisory / Consultancy, Speaker Bureau / Expert testimony: Kite; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche Pharma AG. C. Yang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Hutchison MediPharma Ltd. M. Kania: Shareholder / Stockholder / Stock options, Full / Part-time employment: Hutchison MediPharma Ltd. J. Kauh: Shareholder / Stockholder / Stock options, Full / Part-time employment: Hutchison MediPharma Ltd. N. Ghosh: Advisory / Consultancy, Speaker Bureau / Expert testimony: Seattle Genetics; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pharmacyclics; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Gilead/Kite; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: TG Therapeutics; Advisory / Consultancy: Celgene/Juno.
Resources from the same session
1269 - One-year follow-up results of eribulin for soft-tissue sarcoma including rare subtypes in a real-world observational study in Japan
Presenter: Shunji Takahashi
Session: Poster Display session 1
Resources:
Abstract
2868 - Prevalence of chemotherapy use and its impact on overall survival in patients with bone- and soft tissue sarcomas -A population-based analysis of 3746 patients
Presenter: Herbert Loong
Session: Poster Display session 1
Resources:
Abstract
3042 - Clinical course and therapeutic management of classical and endemic Kaposi’s Sarcoma (C/E KS)
Presenter: Lina Benajiba
Session: Poster Display session 1
Resources:
Abstract
3141 - The final outcomes of study on combined therapy of adult patients with localized synovial sarcoma
Presenter: Katarzyna Kozak
Session: Poster Display session 1
Resources:
Abstract
5449 - Real-world Outcomes of Patients with Locally Advanced or Metastatic Epithelioid Sarcoma
Presenter: Mrinal Gounder
Session: Poster Display session 1
Resources:
Abstract
4465 - SAKK 57/16 Nab-Paclitaxel And Gemcitabine in soft tissue sarcoma (NAPAGE): results from the phase I part of a phase I/II trial
Presenter: Antonia Digklia
Session: Poster Display session 1
Resources:
Abstract
5013 - Outcome of 98 patients with epithelioid sarcoma treated in curative intent: a retrospective study from the French Sarcoma Group (GSF-GETO)
Presenter: Maud Pedrono
Session: Poster Display session 1
Resources:
Abstract
5614 - Comparison of filgrastim and pegfilgrastim prophylaxis in sarcoma patients receiving highly myelosuppressive chemotherapy.
Presenter: Paolo Tarantino
Session: Poster Display session 1
Resources:
Abstract
1033 - Access to clinical trials for soft tissue sarcoma patients in Western and Eastern Europe
Presenter: Vasilii Ostafiichuk
Session: Poster Display session 1
Resources:
Abstract
4094 - Treatment outcomes for adult patients with localized osteosarcoma treated with chemotherapy without methotrexate
Presenter: Marília Silva
Session: Poster Display session 1
Resources:
Abstract