Abstract 641P
Background
The c-Met (MET protein)-directed antibody-drug conjugate telisotuzumab vedotin had promising efficacy in patients (pts) with EGFR wildtype nonsquamous non-small cell lung cancer (NSQ NSCLC) and c-Met protein overexpression (OE). The METRIX study is investigating the prevalence of c-Met protein OE across pt characteristics and is assessing associations with key oncogenic driver mutations.
Methods
This retrospective, international, non-therapeutic study analyzes biopsy/resection specimens from adult pts with advanced/metastatic NSQ NSCLC (Jan 2019–present) for c-Met protein expression by immunohistochemistry (MET SP44 antibody + ultraView detection kit [Ventana Roche]). Twelve countries are participating, aiming to include >500 pts. c-Met protein OE was defined as ≥25% tumor cells with membrane staining at 3+ intensity, and c-Met high OE as ≥50% at 3+. Pt demographics, disease characteristics, and biomarker status were collected locally.
Results
This interim analysis included data from 108 pts from Japan, Canada, Argentina, and Switzerland. Median age was 66 (28–84) yr; 53% were male. Most pts had ECOG 0/1 (42/46%), tumor stage III/IV at initial diagnosis (34/51%), and metastatic disease at study start (71%). A total of 45 (42%) pts had c-Met protein OE; 31 (29%) had high c-Met OE. The prevalence of c-Met OE (OE/high OE) was numerically higher in male (44/37%) vs female (39/20%) pts and in Asian (47/40%) vs White (44/29%) pts. By region, prevalence (OE/high OE) was 47/40% in Asia, 36/24% in Europe, 44/28% in Latin America, and 40/23% in North America. Additional biomarker expression data are listed in the table Table: 641P
Proportion of biomarker expression by c-Met protein status
| Total | c-Met protein OE (≥25%) | c-Met protein high OE (≥50%) | |||
| n=108 | Y n=45 | N n=63 | Y n=31 | N n=77 | |
| EGFR mutation, n/N (%) | 26/102 (25) | 12/44 (27) | 14/58 (24) | 8/30 (27) | 18/72 (25) |
| ALK1 translocation, n/N (%) | 7/100 (7) | 4/43 (9) | 3/57 (5) | 3/30 (10) | 4/70 (6) |
| ROS1 translocation, n/N (%) | 1/99 (1) | 1/41 (2) | 0/58 (0) | 1/29 (3) | 0/70 (0) |
| KRAS, n/N (%) | 30/64 (47) | 15/27 (56) | 15/37 (41) | 9/16 (56) | 21/48 (44) |
| BRAF, n/N (%) | 8/89 (9) | 3/38 (8) | 5/51 (10) | 2/27 (7) | 6/62 (10) |
| RET, n/N (%) | 2/38 (5) | 1/15 (7) | 1/23 (4) | 1/12 (8) | 1/26 (4) |
| PD-L1, mean tumor proportion score (SD)a | 28.3 (35.1) | 47.1 (39.7) | 14.2 (23.0) | 51.6 (40.1) | 18.5 (27.7) |
aMissing data, n=3. N = pts with available test results.
.Conclusions
Prevalence of c-Met protein OE is high in NSCLC, and it is important to identify these pts for the selection of novel therapeutic strategies. Understanding the prevalence of c-Met protein OE in different pt populations and its overlap with other biomarker alterations could aid in therapy decisions. Future results from METRIX will expand these data.
Clinical trial identification
Editorial acknowledgement
Medical writing support was provided by Judith Land, PhD, CMPP, from Aptitude Health, The Hague, the Netherlands, and funded by AbbVie.
Legal entity responsible for the study
AbbVie Inc.
Funding
AbbVie Inc.
Disclosure
H. Horinouchi: Financial Interests, Personal, Research Funding: AbbVie, MSD, Chugai/Roche, Daiichi Sankyo, Janssen, Genomic Health; Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD, Lilly, BMS, Ono, Janssen, Kyowa Kirin, Nihonkayaku. Z. Xu: Financial Interests, Personal, Research Funding: Roche, AstraZeneca, Pfizer, EMD Serono, AbbVie, EXACTIS. S. Savic Prince: Financial Interests, Personal, Other, Scientific services for this non-interventional retrospective study: AbbVie; Financial Interests, Personal, Other, Consultancy: AstraZeneca; Financial Interests, Personal, Advisory Board: Merck. P. Desmeules: Financial Interests, Personal, Research Funding: AstraZeneca, Pfizer, Novartis, Roche, EMD Serrono, Eli Lilly, Amgen, Merck, AbbVie. A. Koslucher, P.J. Ansell, R. Thiébaut, C. Hader: Financial Interests, Personal, Full or part-time Employment: AbbVie; Financial Interests, Personal, Stocks or ownership: AbbVie. All other authors have declared no conflicts of interest.