Abstract 83P
Background
Based on a pivotal phase I/II study (NCT01970865), lorlatinib was approved by the European Medicines Agency for the treatment of patients (pts) with ALK+ mNSCLC whose disease had progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy, or crizotinib and at least one other ALK TKI. Due to the limited number of pts who progressed on 2nd-generation ALK TKIs, a post-approval study was conducted to confirm the efficacy of lorlatinib in this setting.
Methods
In this phase IV open-label study (NCT04362072), adult pts with ALK+ mNSCLC who progressed on 1st-line alectinib or ceritinib were treated with lorlatinib 100 mg once daily. The primary endpoint was confirmed objective response rate (ORR) by independent central review(ICR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), intracranial ORR, all by ICR, and safety.
Results
Among the 71 pts treated with lorlatinib, 85% had received alectinib and 15% had received ceritinib as prior ALK TKI. The median duration of lorlatinib treatment was 9.7 mo (range, 0.3–42.8). The study met its primary endpoint, with confirmed ORR of 42% (95% CI, 31%-55%). The median duration of response follow-up was 18.0 mo (95% CI, 9.6–22.1). Median DOR was not reached, with 65% probability to remain in response for ≥12 mo. Median PFS was 12.2 mo (95% CI, 6.9–22.1) with 51% probability of being progression free at 12 mo. In pts with CNS metastases (n=30), intracranial ORR was 47% (95% CI, 28%-66%). Any-grade treatment-emergent adverse events (TEAEs) occurred in 97% of pts; grade ≥3 occurred in 39%. The most frequent TEAEs were hypercholesterolemia (59%), hypertriglyceridemia (56%), edema (46%), fatigue (27%), and peripheral neuropathy (21%). Serious TEAEs occurred in 32% of pts. TEAEs led to dose reduction in 14% and treatment discontinuation in 13% of pts; none discontinued due to treatment-related AEs.
Conclusions
Efficacy and safety results from this phase IV study of lorlatinib remained consistent with the pivotal phase I/II study. Lorlatinib continued to show clinically meaningful benefit in pts with previously treated ALK+ mNSCLC.
Clinical trial identification
NCT04362072.
Editorial acknowledgement
During the preparation of this work the author(s) used a genAI tool (12/10/24; Pfizer; GPT-4o) to develop the first draft. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication. Editorial assistance was provided by Nucleus Global and was funded by Pfizer.
Legal entity responsible for the study
Pfizer.
Funding
Pfizer.
Disclosure
A. Bearz: Financial Interests, Personal, Invited Speaker: Pfizer, Roche, BMS, Novartis; Financial Interests, Personal, Writing Engagements: Pfizer; Financial Interests, Personal, Advisory Board: Regeneron, Pfizer, Roche, Pierre Fabre. H. Thurm, F. Toffalorio: Financial Interests, Personal, Stocks/Shares: Pfizer. D. Pavlov: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Ownership Interest: Pfizer. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Sharp & Dohme, Novartis, Regeneron, Turning Point, Pfizer, Genmab, Daiichi Sankyo, Johnson & Johnson, ITeos Therapeutics, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme, Gilead, Novartis, Regeneron, Johnson & Johnson, Pierre Fabre; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, Beigene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Financial Interests, Institutional, Invited Speaker: Nuvalent; Non-Financial Interests, Personal, Leadership Role, President (2021–2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulı.? All other authors have declared no conflicts of interest.