Abstract CT223: Updated efficacy and safety from the phase 3 CROWN study of first-line lorlatinib vs crizotinib in advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC)

Abstract Background: Lorlatinib improved progression-free survival (PFS) and demonstrated intracranial (IC) activity in patients (pts) with untreated advanced ALK+ NSCLC in the interim analysis of the randomized, Phase 3, CROWN study of lorlatinib vs crizotinib. We report updated 36-month follow-up data. Methods: 296 pts with previously untreated advanced ALK+ NSCLC were randomized 1:1 to oral lorlatinib (100 mg QD; n=149) or crizotinib (250 mg BID; n=147), stratified by presence of CNS metastases (mets) and ethnicity. Primary endpoint: PFS by blinded independent central review (BICR). Secondary endpoints included overall survival, PFS by investigator, and objective response (OR), IC-OR, IC time to progression (IC-TTP), duration of response (DR), IC-DR (all by BICR), and safety. Results: At data cutoff (Sep 20, 2021), median duration of follow-up for PFS was 36.7 months for lorlatinib and 29.3 months for crizotinib. Median PFS by BICR was NR (95% CI, NR-NR) for lorlatinib and 9.3 months (95% CI, 7.6-11.1) for crizotinib (HR, 0.27; 95% CI, 0.18-0.39). PFS by investigator results were similar (Table). For pts with brain mets at baseline (n=37 lorlatinib/n=39 crizotinib), the HR for IC-TTP for lorlatinib vs crizotinib was 0.10 (95% CI, 0.04-0.27), and for pts without brain mets (n=112/n=108) was 0.02 (95% CI, 0.002-0.14). OR, IC-OR, DR, and IC-DR were all improved with lorlatinib vs crizotinib (Table). All-cause grade 3-4 adverse events (AEs) and AEs leading to treatment discontinuation were reported in 76% and 7% of pts with lorlatinib and 57% and 10% of pts with crizotinib, respectively. No new safety signals emerged. Conclusions: These updated long-term data from CROWN confirm the efficacy of lorlatinib over crizotinib in pts with treatment-naïve ALK+ NSCLC, with no new safety signals detected, and support the use of lorlatinib in pts with untreated ALK+ NSCLC with and without brain mets. Summary of other efficacy resultsa Clinical trial information: NCT03052608 Funding: Pfizer Inc. ITT population Lorlatinib(n=149) Crizotinib(n=147) % alive without progression at:12 mo (95% CI) 78 (70–84) 38 (29–47) 24 68 (60–75) 22 (14–30) 36 64 (55–71) 19 (12–27) Median PFS by investigator, mo (95% CI) NR (NR–NR) 9.1 (7.4–10.9) HR (95% CI) 0.19 (0.13–0.27) Confirmed OR, n (%) [95% CI] 115 (77) [70–84] 86 (59) [50–67] Median DR,b mo (95% CI) NR (NR–NR) 9.6 (9.0–12.9) Patients with measurable or nonmeasurable brain metastases at baseline (n=37) (n=39) Median PFS, mo (95% CI) NR (18.2–NR) 7.2 (3.7–9.2) HR (95% CI) 0.21 (0.10–0.44) Confirmed IC-OR, n (%) [95% CI] 24 (65) [48–80] 7 (18) [8–34] Complete response, n (%) 22 (60) 5 (13) Median IC-DR,b mo (95% CI) NR (NR–NR) 9.4 (6.0–11.1) Patients without brain metastases at baseline (n=112) (n=108) Median PFS, mo (95% CI) NR (NR–NR) 11.0 (9.0–14.6) HR (95% CI) 0.29 (0.19–0.44) aBy blinded independent central review unless stated otherwise. bIn patients with a confirmed complete or partial response. CI, confidence interval; DR, duration of response; HR, hazard ratio; ITT, intention- to-treat; NR, not reached; IC, intracranial; OR, objective response; PFS, progression-free survival. Citation Format: Benjamin Solomon, Todd Bauer, Tony Mok, Geoffrey Liu, Julien Mazieres, Filippo de Marinis, Yasushi Goto, Dong-Wan Kim, Yi-Long Wu, Mikhail Dvorkin, Jacek Jassem, Froylán López-López, Ross Soo, Anna Polli, Elisa Dall'O, Laura Iadeluca, Francesca Toffalorio, Enriqueta Felip. Updated efficacy and safety from the phase 3 CROWN study of first-line lorlatinib vs crizotinib in advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT223.