Phase Ib study of eprenetapopt (APR-246) in combination with pembrolizumab in patients with advanced or metastatic solid tumors.

Abstract

BACKGROUND:

We conducted a phase I, multicenter, open-label, dose-finding, and expansion study to determine the safety and preliminary efficacy of eprenetapopt (APR-246) combined with pembrolizumab in patients with advanced/metastatic solid tumors (ClinicalTrials.gov NCT04383938).

PATIENTS AND METHODS:

For dose-finding, requirements were non-central nervous system primary solid tumor, intolerant to/progressed after ≥1 line of treatment, and eligible for pembrolizumab; for expansion: (i) gastric/gastroesophageal junction tumor, intolerant to/progressed after first-line treatment, and no prior anti-programmed cell death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy; (ii) bladder/urothelial tumor, intolerant to/progressed after first-line cisplatin-based chemotherapy, and no prior anti-PD-1/PD-L1 therapy; (iii) non-small-cell lung cancer (NSCLC) with previous anti-PD-1/PD-L1 therapy. Patients received eprenetapopt 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle. Primary endpoints were dose-limiting toxicity (DLT), adverse events (AEs), and recommended phase II dose (RP2D) of eprenetapopt.

RESULTS:

Forty patients were enrolled (median age 66 years; range 27-85) and 37 received eprenetapopt plus pembrolizumab. No DLTs were reported and the RP2D for eprenetapopt in combination was 4.5 g/day IV on days 1-4. The most common eprenetapopt-related AEs were dizziness (35.1%), nausea (32.4%), and vomiting (29.7%). AEs leading to eprenetapopt discontinuation occurred in 2/37 patients (5.4%). In efficacy-assessable patients (n = 29), one achieved complete response (urothelial cancer), two achieved partial responses (NSCLC, urothelial cancer), and six patients had stable disease.

CONCLUSIONS:

The eprenetapopt plus pembrolizumab combination was well tolerated with an acceptable safety profile and showed clinical activity in patients with solid tumors.

• Authors: H Park, G I Shapiro, X Gao, A Mahipal, J Starr, M Furqan, P Singh, A Ahrorov, L Gandhi, A Ghosh, D Hickman, P D Gallacher, A Wennborg, E C Attar, M M Awad, S Das, E E Dumbrava
• Journal: ESMO open (ESMO Open) Vol. 7 Issue 5 Pg. 100573 (10 2022) ISSN: 2059-7029 [Electronic] England
• PMID: 36084396 (Publication Type: Clinical Trial, Phase I, Multicenter Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Chemical References

• eprenetapopt
• pembrolizumab
• Quinuclidines

Topics

• Adult
• Aged
• Aged, 80 and over
• Humans
• Middle Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Neoplasms (drug therapy, pathology)
• Quinuclidines (therapeutic use)