162P - Tailoring patient molecular selection for novel anti-MET therapies

Background

Previous strategies inhibiting MET included monoclonal antibodies (mAb) and tyrosine kinase inhibitors (TKI), with scarce efficacy partly due to the lack of robust predictive biomarkers. Next-generation antibody drug conjugates (ADCs) represent a novel strategy relying on minimal target expression rather than downstream signaling. MET overexpression occurs in 30-50% of solid tumors and preclinical models suggest ADC activity independent of MET copy number alteration (CNA). We aimed to analyze tumors harboring MET CNA and to describe early efficacy signals with novel MET-targeted drugs.

Methods

Retrospective multicenter study in adult patients with metastatic solid tumors assessed through the molecular PRE-screening program at ICO (PREICO). Lung cancer patients were not included. Tumor samples were analyzed using Illumina TruSight Oncology 500 NGS panel. Cases were reviewed by a dedicated molecular board and the threshold for MET amplification (amp) was considered CNA ≥2.

Results

From Mar22 to Mar24, we detected 13% cases METamp among 249 pt enrolled in the PREICO program, with median MET CNA of 4.7. Most common METamp tumors were colorectal (CRC) 32%, melanoma 13%, upper-gastrointestinal 13% and urologic 13%, including 27% of a miscellaneous group. Median age was 61 and median previous lines were 2.5. About 60% METamp pt were deemed suitable for therapy: 12 pt received standard of care therapies, whilst 8 pt were enrolled in clinical trials. Noteworthy, two pt were treated with targeted drugs: a KRAS/BRAF wild-type METamp (CNA 5) CRC after anti-EGFR who received a novel MET TKI achieving disease stabilization lasting 4 months (m), and another METamp (CNA 4) adenosquamous gastric cancer who had progressed after 2 prior lines was treated with an ADC anti-MET topoisomerase-1 inhibitor and maintains partial response >4m.

Conclusions

Our study illustrates that almost 13% refractory cancer patients harbour METamp tumors. New cleverly designed drugs demand a more refined approach to improve patient selection, rescuing previously rejected targets (CNA ≥2 but ≤6) or tumor subtypes with a dismal prognosis. Further efforts are warranted to widen molecular pre-screening programs fostering early identification of pt candidates.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.