ALK rearrangement

P2, N=19, Not yet recruiting, Shanghai Chest Hospital

P=N/A, N=56, Active, not recruiting, Fudan University | Not yet recruiting --> Active, not recruiting | Trial completion date: Jun 2024 --> Aug 2026 | Trial primary completion date: Jun 2023 --> Apr 2026

P2, N=10, Terminated, National Cancer Institute (NCI) | Trial completion date: Mar 2027 --> Mar 2026 | Active, not recruiting --> Terminated; Inadequate accrual rate

P=N/A, N=38, Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University); Jiangsu Province Hospital (The First Affiliated Hospital wi

CD8+ T cell infiltration may be associated with the alectinib efficacy in ALK-rearranged NSCLC. Anti-angiogenic therapies may enhance antitumor immunity and thereby augment the efficacy of alectinib as well as that of ICIs for such tumors.

This case documents an unusual presentation of localized pleural dissemination without pathologically confirmed nodal involvement in a central ALK-rearranged lung adenocarcinoma. It highlights the importance of intraoperative pathological confirmation, accurate staging, and timely molecular testing. However, mechanistic and therapeutic implications should be interpreted cautiously in light of the single-case nature of this report.

Patients with driver alterations had lower overall discontinuation rates in subsequent therapy lines, highlighting the need for effective, tolerable treatments for those without driver alterations. Notably, a substantial proportion of patients with targetable driver alterations did not receive the corresponding TKI, underscoring real-world gaps in biomarker-directed treatment implementation.

Stage III ALK-positive NSCLC is prone to relapse but local therapy combined with adjuvant ALK TKIs offers a promising strategy. Patients with EML4-ALK v1 mutations may show improved outcomes.

However, the observed outcomes should be interpreted within the context of patient selection. The enrichment for prior responders limits the generalizability to unselected post-TKI populations, including those with primary resistance.

The HEATR5B-ALK fusion is targetable by ensartinib, producing durable disease control and excellent tolerability. Comprehensive NGS and ALK IHC are essential for detecting rare actionable ALK variants.

Due to rapid enrollment, the target sample size was expanded to 28 patients. The primary endpoint is objective response rate confirmed by central assessment; secondary endpoints include duration of response, progression-free survival, overall survival, and safety.Clinical trial registration: jRCT2041210148 (https://jrct.mhlw.go.jp).

P=N/A, N=240, Completed, Bristol-Myers Squibb