Details

Autor(en) / Beteiligte

• Heist, Rebecca Suk
• Motwani, Monica
• Barlesi, Fabrice
• Goldman, Jonathan Wade
• Kelly, Karen
• Sun, Yan
• Wu, Jun
• Bach, Bruce Allen
• Camidge, D. Ross

Titel

c-Met expression and response to telisotuzumab vedotin (teliso-v) in patients with non-small cell lung cancer

Ist Teil von

• Journal of clinical oncology, 2019-05, Vol.37 (15_suppl), p.9023-9023

Erscheinungsjahr

2019

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Abstract only 9023 Background: c-Met overexpression (OE) and MET amplification (amp) are prognostic of poor outcome for non-small cell lung cancer (NSCLC). Telisotuzumab vedotin (ABBV-399; teliso-v [T]), an anti–c-Met Ab and monomethyl auristatin E drug conjugate, showed efficacy as monotherapy (mono) and combined with erlotinib (T+Er) in a phase 1/1b trial (NCT02099058) in NSCLC patients (pts) with c-Met OE. Here, c-Met OE (by immunohistochemistry [IHC]) and its association with T efficacy were explored. IHC, mRNA, and amp platforms for MET were also compared. Methods: Archival tissue from pts with NSCLC in the phase 1/1b trial was examined. c-Met was assessed centrally by IHC with SP44 Ab (Ventana Medical Systems) and pts with c-Met OE (membrane H-score [H-S] of ≥150) were enrolled. MET mRNA expression was analyzed from total RNA and sequenced on HiSeq 3000 (Illumina). MET amp was analyzed by FISH ( MET/ CEP7 ratio of ≥2) or whole-exome sequencing (copy number ≥2). Efficacy in the T mono every 2 (TQ2W) or 3 (TQ3W) weeks and the T+Er EGFR mutant cohorts was assessed for IHC H-S ≥150 and ≥225. Results: As of Dec 2018, 238 pts with NSCLC were screened centrally for c-Met OE. Of these, 118 pts were enrolled. For screened pts, 76%/37% of nonsquamous (NSQ, n = 201) and 58%/16% of squamous (SQ, n = 32) pts had H-S ≥150/≥225; 75%/41% of NSQ and 55%/16% of SQ NSCLC pts had ≥50% cells with 2+/3+ staining intensity. MET amp was reported for 5 pts, all with high H-S (≥270); there was an association between MET amp and MET RNA levels (n = 4) (t-test p value: 0.0002). See Table for ORR and median PFS by H-S and T treatment. Conclusions: c-Met expression prevalence in NSCLC showed a similar trend as in previous reports. In T+Er-treated pts, ORR was higher for those with c-Met H-S ≥225 than ≥150– < 225, suggesting that biomarker expression may act as an effect size multiplier. Optimization of the c-Met IHC cutoff warrants further investigation. Clinical trial information: NCT02099058. [Table: see text]