Lorlatinib in TKI-naïve patients with advanced ALK-positive non-small cell lung cancer (NSCLC) from India.

e20679 Background: Lorlatinib is a novel brain penetrant 3rd generation anaplastic lymphoma kinase (ALK)- inhibitor, approved as frontline & subsequent line therapy in ALK-rearranged advanced non-small cell lung cancer (NSCLC). However, data on its safety and effectiveness as first-line (1L) therapy in the Indian population remains limited. This study presents an interim analysis of real-world data of 1L Lorlatinib in TKI-naïve ALK-positive advanced NSCLC patients in India. Methods: This is an ongoing ambispective, non-interventional real-world study involving 9 centers across India. All patients diagnosed with ALK-positive advanced NSCLC with or without brain metastases, TKI naïve, receiving lorlatinib in the first line setting & willing to participate can be enrolled. Primary objective of the study is 18-month Progression Free Survival (PFS) rate. This interim analysis has been conducted to assess early response and safety outcomes in the first 51 patients enrolled. A descriptive analysis was conducted on the entire cohort of 51 patients however, Objective Response rate (ORR) and early safety was analyzed for the retrospective cohort & for the prospective patients with at least 1 follow-up (n = 39). Results: From May 2024 - Dec 2024, a total of 51 patients (36 retrospective & 15 prospective) were enrolled in the study. The median age observed was 51 years & Male : Female ratio was 29:22. 94.1% (n = 48) had metastatic disease at the time of Lorlatinib initiation and 49% (n = 25) had brain metastases at baseline. 7.8% patients had received prior brain radiotherapy & 72.5% had an ECOG performance-status score of 1. At median follow up of 8 months within the cohort of 39 patients, the ORR was 74.4% (n = 30 of 39). The best response for 66.7% (n = 26) patients was partial response (PR), 15.3% (n = 6) stable disease (SD), 10.3% (n = 4) complete response (CR) and 7.7% (n = 3) reported progression.17 patients were evaluated for intracranial response and the Intra-cranial Objective response rate (IC-ORR) was 70.6%. 21.1% (n = 4) achieved CR in the brain, 42.1% (n = 8) had PR & 15.8% (n = 3) had SD. On safety analysis, 84.6% (n=33) reported at least one adverse event (AE) of any grade. Hypertriglyceridemia (36.4%) was the most reported AE followed by hypercholesterolemia (27.3%). Pedal edema was observed in 18.2% & weight gain in 15.2% patients. Mood effects were observed in 2 patients. Majority of AEs were mild to moderate (Grade 1/2) in severity & managed either with concomitant medication or resolved on their own. 10.3% (n = 4 of 39) required temporary dose interruptions and 10.3% (n = 4 of 39) patients had permanent treatment discontinuation – 3 had disease progression and 1 due to AE. No dose reductions were reported. Conclusions: Consistent with CROWN trial data, the preliminary results from this real-world study with 1L Lorlatinib in ALK positive advanced NSCLC in the Indian population supports its effectiveness as well as tolerability profile.