1282P - Activity of brigatinib based on genomic alterations detected on ctDNA at baseline and at progression in ALK inhibitor-naïve advanced ALK+ NSCLC from the ALTA-1L trial

Background

Liquid biopsy can identify ctDNA genomic alterations (GAs) in ALK+ non-small cell lung cancer (NSCLC), both at baseline (B) and at treatment resistance (PD) that may assist in upfront treatment selection. However, there is limited data for 2^nd generation ALK inhibitors in 1^st line (1L). Here, we present the activity of 1L brigatinib based on ctDNA GAs at B and PD from the ALTA-1L trial.

Methods

Ancillary study of patients (pts) with ALK+ advanced NSCLC enrolled in ALTA-1L study. We analyzed the ctDNA- NGS available (ctDx Lung NGS, Bioscience) at B and PD of pts treated with brigatinib. We analyzed the co-occurring GAs and ALK fusions at B and at PD. Primary endpoint: Progression-free survival (PFS). Secondary endpoints: overall survival (OS); post1L OS (surrogate of subsequent lines).

Results

In 136 pts assessed, 124 pts were analyzed at B and 66 at PD. Median (m) follow-up was 42.4 months (mo.) (CI 95% 41.7-43.2). At B, ALK fusion was detected in 66/124 (53,2%): EML4-ALK in 56 pts (85%); others in 10 pts (TTN, DCTN1, HIP1, etc.), and not detected in 58. Co-occurring GAs were detected in 67/124 (54%), including TP53 (40), MET (14), EGFR (13), etc. None was detected in 57. At PD, acquired ALK mut. were only detected in 2/66 (3%), non-ALK alt. in 33/66 (50%) and none in 31. Among non-ALK alt.: in 22 were already present at (B) but emerged at PD in 8 (12%); 2 were not assessable (no ctDNA at B). Overall, mPFS and mOS of brigatinib were 24 mo. (95% CI 21.1-44.1) and not reached (NR) (40.6-NR), respectively; 5y-OS rate was 70.8%. PFS was significantly longer in absence of co-occurring GAs, with mPFS of 44.1 mo (23.9-NR) vs. 18.4 mo (11.0-26.9) for those with ≥1 ctDNA GAs (p=0.002). Similar data was observed in OS, with a 5y-OS rate of 78.2% if non-occurring ctDNA GAs vs. 61.1% for those with ≥1 GAs (p=0.05). At PD, the mOS post1L more prolonged was in the none detected group with 19.6 mo. (9.1-NR) vs. 17 mo. in the ALKm group vs. only 7 mo. in case of non-ALK group (p=0.4).

Conclusions

Baseline ctDNA data impacts the PFS/OS in ALK+ NSCLC and may serve as biomarker for guiding treatment selection upfront. Brigatinib achieved prolonged PFS, especially in no-occurring GAs. ctDNA data can influence outcomes in subsequent lines postbrigatinib.

Clinical trial identification

NCT02737501.

Editorial acknowledgement

Legal entity responsible for the study

IDIBAPS.

Funding

Has not received any funding.

Disclosure

L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, Roche, AstraZeneca, MSD, Janssen; Financial Interests, Personal, Invited Speaker: Takeda, Roche, BMS, AstraZeneca, Janssen; Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI; Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS; Financial Interests, Institutional, Research Grant, COVID research Grant: AMGEN; Financial Interests, Institutional, Coordinating PI, Cover cost of molecular test.: INIVATA; Financial Interests, Institutional, Coordinating PI: GILEAD; Financial Interests, Institutional, Coordinating PI, Beca SEOM Grupo Emergente 2022: AstraZeneca. C. Teixido: Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck Sharp & Dohme, Roche Farma, Diaceutics, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: Novartis, AstraZeneca. A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Amgen, Bayer, AstraZeneca, Boehringer Ingelheim, Jansen, Mirati; Financial Interests, Institutional, Invited Speaker: Lilly, Jansen; Financial Interests, Institutional, Other, IDMC: Roche; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Local PI: Lilly, Amgen, Daiichi Sankyo, JNJ, Mirati; Financial Interests, Institutional, Coordinating PI: Roche; Financial Interests, Institutional, Steering Committee Member: Roche; Non-Financial Interests, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Member: IASCL, ASCO, AACR. All other authors have declared no conflicts of interest.