PS02.22 Alectinib Following Prior ALK Tyrosine Kinase Inhibitor (TKI) Therapy: Results from the US Expanded Access Program (EAP): Topic: Medical Oncology

Patients with anaplastic lymphoma kinase rearrangements (ALK+) account for 4–7% of non-small-cell lung cancer (NSCLC) cases. Clinical studies have shown ALK inhibitors (ALKi) to be effective treatments for these patients. The ALKi alectinib received accelerated US Food and Drug Administration (FDA) approval in 2015 for the treatment of patients with ALK+ NSCLC who have progressed on, or are intolerant to crizotinib. The objective of this expanded access program (EAP) was to provide access to alectinib following prior ALK TKI therapy for patients with ALK+ NSCLC. Here we report data collected during this EAP. Following screening, patients received alectinib (600 mg BID) until disease progression, unacceptable toxicity, consent withdrawal, death, or commercial availability in the US following FDA approval. Efficacy outcomes were objective response rate (ORR; RECIST by investigator) and disease control rate (DCR; RECIST by investigator). Key safety outcomes were adverse events (AEs) and incidence of dose interruptions, reductions and withdrawals. The median age of the safety population (n=128) was 55 years, and the majority had never smoked (n=86, 67.2%). In total, 77.3% (n=99) had central nervous system (CNS) metastases at baseline, of whom 65.7% (n=65) had received treatment for their CNS metastases, most commonly whole brain radiation therapy (n=35, 53.8%) or radiosurgery (n=20, 30.8%). All patients had received prior ALKi therapy (crizotinib, 98.4%; ceritinib, 46.1%; other, 3.9%) and 53.9% had received prior non-ALKi therapy. In the efficacy evaluable population (n=90), ORR was 34.4% (95% CI 24.7–45.2) and DCR was 73.3% (95% CI 63.0–82.1). In patients who had received one prior ALKi (n=46, of whom n=44 received crizotinib), ORR was 41.3% (95% CI 27.0–56.8) and DCR was 78.3% (95% CI 63.6–89.1). Mean treatment duration was 23.91 weeks; 104 patients (81.3%) received a dose intensity >90–100%. Incidence and types of AEs were similar to those previously described from alectinib clinical trials: 27.3% of patients reported at least one grade ≥3 AE, most commonly disease progression (2.3%), acute kidney injury (1.6%) and elevated ALT or AST (1.6% each). Alectinib was well tolerated as reflected by the low rates of dose interruptions (21.9%), reductions (9.4%) and discontinuations (13.3%). Alectinib demonstrated robust efficacy following prior lines of ALKi therapy, and an acceptable safety profile in patients with previously treated ALK+ NSCLC in this EAP.