Phase Ib study of eprenetapopt (APR-246) in combination with pembrolizumab in patients with advanced or metastatic solid tumors Journal Article
| Authors: | Park, H.; Shapiro, G. I.; Gao, X.; Mahipal, A.; Starr, J.; Furqan, M.; Singh, P.; Ahrorov, A.; Gandhi, L.; Ghosh, A.; Hickman, D.; Gallacher, P. D.; Wennborg, A.; Attar, E. C.; Awad, M. M.; Das, S.; Dumbrava, E. E. |
| Article Title: | 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. © 2022 The Author(s) |
| Keywords: | adult; clinical article; treatment response; aged; gene mutation; clinical trial; constipation; drug tolerability; fatigue; advanced cancer; cancer growth; diarrhea; drug efficacy; drug safety; drug withdrawal; side effect; follow up; metastasis; anemia; nausea; vomiting; myalgia; cohort analysis; bladder cancer; protein p53; cancer mortality; abdominal pain; arthralgia; backache; dizziness; dyspnea; fever; hyperglycemia; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; confusion; hyponatremia; hypotension; maculopapular rash; multicenter study; muscle weakness; stomach cancer; open study; alkaline phosphatase blood level; headache; physical examination; maximum tolerated dose; phase 1 clinical trial; good clinical practice; transitional cell carcinoma; tremor; electrocardiogram; dose calculation; national health organization; p53; solid tumors; hemoptysis; vital sign; non small cell lung cancer; vertigo; decreased appetite; overall response rate; Common Terminology Criteria for Adverse Events; very elderly; human; male; female; article; pembrolizumab; medical dictionary for regulatory activities; treatment interruption; solid malignant neoplasm; eprenetapopt |
| Journal Title: | ESMO Open |
| Volume: | 7 |
| Issue: | 5 |
| ISSN: | 2059-7029 |
| Publisher: | European Society for Medical Oncology |
| Date Published: | 2022-10-01 |
| Start Page: | 100573 |
| Language: | English |
| DOI: | 10.1016/j.esmoop.2022.100573 |
| PUBMED: | 36084396 |
| PROVIDER: | scopus |
| PMCID: | PMC9588880 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 October 2022 -- Source: Scopus |
