NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922)

Summary

Lorlatinib is a novel inhibitor across ALK variants, including those resistant to crizotinib. In this first pediatric phase 1 trial of lorlatinib, the drug will be utilized as a single agent and in combination with chemotherapy in patients with relapsed/refractory neuroblastoma. The dose escalation phase of this study (Cohort A1) uses a traditional Phase I 3+3 design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 6 patients (Cohort B1), within which ALKi naïve patients will be prioritized, will be initiated. Parallel cohorts will be initiated in adults or patients with large BSA (Cohort A2) and in combination with chemotherapy upon establishing RP2D (Cohort B2).

Timeline

Start

2017-09-05

Primary completion

2024-08-22

Completion

2025-01-31

Outcome

Met primary endpoint

paper we report here on three cohorts that have met pre-specified primary endpoints PMID 37012551 ↗

Publications

• Goldsmith KC, Park JR, Kayser K, Malvar J, Chi YY, Groshen SG, Villablanca JG, Krytska K, Lai LM, Acharya PT, Goodarzian F, Pawel B, Shimada H, Ghazarian S, States L, Marshall L, Chesler L, Granger M, Desai AV, Mody R, Morgenstern DA, Shusterman S, Macy ME, Pinto N, Schleiermacher G, Vo K, Thurm HC, Chen J, Liyanage M, Peltz G, Matthay KK, Berko ER, Maris JM, Marachelian A, Mosse YP. Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results. Nat Med. 2023 May;29(5):1092-1102. doi: 10.1038/s41591-023-02297-5. Epub 2023 Apr 3.
• Baranowska-Kortylewicz J, Kortylewicz ZP, McIntyre EM, Sharp JG, Coulter DW. Multifarious Functions of Butyrylcholinesterase in Neuroblastoma: Impact of BCHE Deletion on the Neuroblastoma Growth In Vitro and In Vivo. J Pediatr Hematol Oncol. 2022 Aug 1;44(6):293-304. doi: 10.1097/MPH.0000000000002285. Epub 2021 Sep 6.

Drugs

Indications