P45.08 Lorlatinib for Previously Treated ALK-Positive Advanced NSCLC: Primary Efficacy and Safety Data from a Phase 2 Study in China

Abstract

Lorlatinib, a third-generation inhibitor of anaplastic lymphoma kinase (ALK), was shown in a global Phase 2 study to have potent overall and intracranial (IC) anti-tumor activity in patients with ALK-positive advanced non-small cell lung cancer (NSCLC) after progression on first- and/or second-generation ALK inhibitors (NCT01970865). Here we report primary data from a multicenter Phase 2 study conducted in China that investigated lorlatinib in ALK inhibitor-treated patients with ALK-positive NSCLC (NCT03909971). This ongoing, open-label, Phase 2 study enrolled patients in China with ALK-positive locally advanced/metastatic NSCLC and disease progression after crizotinib as the only ALK-inhibitor (Cohort 1), or after one ALK-inhibitor other than crizotinib, with or without prior crizotinib (Cohort 2). Patients with CNS metastases were eligible to enroll; one prior line of chemotherapy was permitted. All patients received lorlatinib 100 mg QD in a continuous 3-week cycle. The primary endpoint was objective response rate (ORR) by independent central review (ICR) per RECIST v1.1 in Cohort 1. Secondary endpoints included ORR in Cohort 2, IC-ORR, PFS, overall survival (OS), and safety. In total, 109 patients were enrolled: 67 to Cohort 1 and 42 to Cohort 2. Among these, 36 patients in Cohort 1 and 21 patients in Cohort 2 had ≥1 intracranial lesion at baseline per ICR assessment. At data cutoff (August 10, 2020), ORR (95% CI) by ICR in Cohort 1 was 70.1% (57.7–80.7) and in Cohort 2 was 47.6% (32.0–63.6). IC-ORR was 80.6% in Cohort 1 and 47.6% in Cohort 2. See Table for additional response data. Median DOR by ICR was not reached in Cohort 1, and was 11.2 months in Cohort 2. Median PFS by ICR was not reached in Cohort 1, and was 5.6 months in Cohort 2. OS data were immature and median OS was not estimatable in either cohort. Median treatment duration was 11.4 months in Cohort 1 and 8.4 months in Cohort 2. Grades 3–4 treatment-related adverse events (TRAEs) occurred in 36 (53.7%) patients in Cohort 1 and 17 (40.5%) patients in Cohort 2; serious TRAEs occurred in 4 (6.0%) and 5 (11.6 %) patients in each cohort, respectively. No Grade 5 TRAE were reported in either cohort. The most commonly-reported any-grade AEs overall were hypercholesterolemia (92.7%) and hypertriglyceridemia (91.7%).Table 1Summary of response dataCohort 1Cohort 2TotalBest overall response by ICRPatients in analysisN=67N=42N=109ORR, n (%)47 (70.1)20 (47.6)67 (61.5)95% CI57.7–80.732.0–63.651.7–70.6CR8 (11.9)2 (4.8)10 (9.2)PR39 (58.2)18 (42.9)57 (52.3)SD8 (11.9)6 (14.3)14 (12.8)Best overall intracranial response in patients with any intracranial lesionsPatients in analysisN=36N=21N=57IC-ORR, n (%)29 (80.6)10 (47.6)39 (68.4)95% CI64.0–91.825.7–70.254.8–80.1CR19 (52.8)6 (28.6)25 (43.9)PR10 (27.8)4 (19.0)14 (24.6)SD02 (9.5)2 (3.5)CI, confidence interval; CR, complete response; IC, intracranial; ICR, independent central review; ORR, objective response rate; PR, partial response; SD, stable disease Open table in a new tab CI, confidence interval; CR, complete response; IC, intracranial; ICR, independent central review; ORR, objective response rate; PR, partial response; SD, stable disease Lorlatinib showed robust clinical activity in Chinese patients with previously treated ALK-positive NSCLC, including those with CNS metastases. Safety data were consistent with previous findings.