1362P - Association of baseline (BL) anaplastic lymphoma kinase (ALK) fusion detected by circulating tumor DNA (ctDNA) with clinical features and outcomes in the phase III ALTA-3 trial

Background

In ALTA-3 (NCT03596866), treatment with brigatinib and alectinib showed similar efficacy in patients (pts) with ALK+ NSCLC. We report the results of an exploratory correlative pooled analysis of the association of BL ALK fusion status, as detected by ctDNA, with clinical features and outcomes in ALTA-3.

Methods

ALTA-3 was a randomized, open-label study of brigatinib 180 mg once daily (7-day lead-in at 90 mg) vs alectinib 600 mg twice daily in pts with advanced ALK+ NSCLC after progression on crizotinib. For this analysis, ALK fusion detection in plasma at BL by ctDNA sequencing was correlated with clinical features (tumor size, target lesion number, organ site involvement, smoking status) and outcomes (median progression-free survival [mPFS; estimated by Kaplan-Meier methods]). ctDNA sequencing was conducted retrospectively with AmoyDx (Chinese pts) and Resolution Bio ctDx™ next-generation sequencing panels. Tumor size was represented as sum of the longest diameter (SLD) of target lesions (RECIST v1.1 criteria). Association between ALK status and clinical features was estimated by odds ratios (OR).

Results

Of 248 pts in ALTA-3, ctDNA from plasma collected at BL from 232 pts was sequenced. ALK fusions were detected in 78 (ALK ctDNA+) and not detected in 154 (ALK ctDNA−). ALK ctDNA− pts had longer mPFS compared with ALK ctDNA+ pts (mPFS 22.5 vs 11.1 months, respectively; hazard ratio 0.48; 95% confidence interval [CI] 0.32–0.71; P=0.0002). ALK ctDNA− pts were more likely to have SLD less than or equal to the median (39 mm) compared with ALK ctDNA+ pts (OR 0.32, 95% CI 0.17–0.59). ALK ctDNA+ status was associated with >1 (median) BL target lesion (OR 0.27, 95% CI 0.14–0.50) and >3 (median) involved organ sites (OR 0.40, 95% CI 0.21–0.73). Smoking status did not impact ctDNA detection of ALK fusion status or outcomes.

Conclusions

Detectable BL ALK fusion by plasma ctDNA is an indicator of poor prognosis and is associated with increased tumor size, number of metastases, and organ site involvement. ALK fusion detection using BL ctDNA could be a surrogate for disease burden and may identify pt populations for escalation strategies in the future.

Clinical trial identification

NCT03596866.

Editorial acknowledgement

Medical writing and editorial support was provided by Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA.

Legal entity responsible for the study

Takeda Development Center Americas, Inc.

Funding

Takeda Development Center Americas, Inc.

Disclosure

C. Aggarwal: Financial Interests, Institutional, Research Funding: AstraZeneca, Genentech, Incyte, Macrogenics, Medimmune, and Merck Sharp & Dohme; Financial Interests, Personal, Other, Consultation fees: Genentech, Lilly, Celgene Merck, AstraZeneca, Blueprint Genetics, Shionogi, Daiichi Sankyo/ AstraZeneca, Regeneron/ Sanofi, Eisai, BeiGene, Turning Point, Pfizer, Janssen, Boehringer Ingelheim. A. Barakat, X. Tong, A. Krueger, B. Hupf, R. Fram, S. Vincent: Financial Interests, Personal, Full or part-time Employment: Takeda.