Efficacy and safety of alectinib in pediatric and adult patients with ALK altered advanced solid tumors: Results from the TACKLE phase II trial, a MASTER KEY substudy (NCCH1712/MK003).

Abstract

3105 Background: Alectinib is an orally administered tyrosine kinase inhibitor that targets anaplastic lymphoma kinase (ALK) and is approved in ALK-positive non-small cell lung cancers and anaplastic large cell lyphomas in Japan. Beyond these, there is a rare population carrying the same ALK alteration regardless of cancer type, often referred to as “ALKomas”. Treatment options are limited for these ALK altered solid tumors. Methods: This open-label phase II study evaluated alectinib for ALK altered locally advanced or metastatic cancer. Patients received alectinib as either a capsule or a suspension. Primary endpoint was central-assessed confirmed objective response rate (ORR) according to RECIST v1.1. A Bayesian approach was used to evaluate eligible patients in the main cohort, which were patients able to ingest capsules. Expected ORR was set at 40% and a threshold at 10%. Secondary endpoints included safety, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: 26 patients, aged from 8 months to 78 years, across 11 tumor types received treatment. The most common tumor type was soft tissue sarcoma (STS) (n = 11) followed by embryonal neoplasm (n = 5). Alterations included fusion/rearrangements (n = 19), mutations (n = 5), and amplifications (n = 2). The median follow-up was 15.0 months. In the evaluable patients of the main cohort (n = 16), the central-assessed ORR was 43.8% (95% CI, 19.8 to 70.1), meeting the decision criteria of the Bayesian design for the primary endpoint. For the entire evaluable patients (n = 24), the central-assessed ORR was 54.2% (32.8 to 74.4), the DCR was 70.8% (48.9 to 87.4); the median PFS was 24.9 months (3.9 to not estimable); and the median OS was 38.8 months (13.9 to not estimable). In patients with ALK fusions/rearrangements (n = 17), the ORR was 76.5 % (50.1 to 93.2), DCR 82.4% (56.6 to 96.2) and the median PFS and OS were both not reached. All patients with inflammatory myofibroblastic tumor showed a response (ORR 100%, n = 8/8). In pediatric patients aged 15 and under (n = 11), the ORR was 63.6% (30.8 to 89.1) with a DCR of 100.0% (71.5 to 100.0). Although no responses were observed in the patients with ALK mutations or amplifications, a clinically meaningful stable disease was observed in 3 of 5 ALK mutated patients. Grade ≥3 drug-related adverse events were observed in 15.4% (n = 4) among all treated patients (n = 26), with no drug related deaths. Conclusions: Our study showed that patients with ALK alterations treated with alectinib achieved sustained clinical benefit, meaningful survival outcomes, and safety consistent with previous data. Greatest benefit was observed for the ALK fusion population including pediatric patients. These data support the potential role of alectinib as a tumor-agnostic therapy for both pediatric and adult patients with ALK altered solid tumors. Clinical trial information: jRCT2091220364 .