1382P - Liquid biopsies (LBx) and tissue biopsies (TBx) for identifying MET exon 14 (METex14) skipping in advanced NSCLC: Analyses from the phase II VISION study of tepotinib

Background

LBx and TBx have complementary roles in detection of NSCLC driver alterations, such as METex14, which predicts efficacy of MET inhibitors. The only MET inhibitor trial to enroll based on prospective detection of METex14 in LBx and/or TBx is the VISION trial of tepotinib. We evaluated patient (pt) characteristics and outcomes according to METex14 positivity in LBx and/or TBx (data cut-off: Nov 20, 2022).

Methods

METex14 was centrally assessed in prescreening by NGS analysis of fresh LBx (Guardant360® or Archer®MET) and/or archival or fresh TBx (Oncomine Focus or Archer®MET). Pts in Japan could enroll based on local TBx RT-PCR via the LC-SCRUM program. Parallel LBx/TBx testing was recommended but not mandatory. Eligibility required LBx-positive (L+) and/or TBx-positive (T+) status.

Results

Of 313 pts, 208 (66.5%) were T+ and 178 (56.9%) were L+. L+ pts had worse baseline prognostic features than T+ pts, including more pts with ≥3 target lesions (27.5% vs 18.8%) or ECOG PS 1 (76.4% vs 72.1%), higher median sum of target lesion diameters (67.1 vs 55.2 mm) and worse health-related quality of life (mean EORTC QLQ-C30 GHS, 53.9 vs 60.1). In 180 T+ pts with matching LBx results, METex14 was detected in ctDNA (L+) in 74 (41.1%) (i.e. T+/L+) and was undetectable (L–) in 106 (58.9%) (i.e. T+/L–). ORRs were slightly higher in T+/L+ pts, but T+/L– pts had longer DOR, PFS and OS. Overall meaningful durable efficacy was seen in treatment-naive and previously treated pts (Table).

Conclusions

Tepotinib had robust and durable activity in T+ pts with L– or L+ status. While both LBx and TBx are suitable and complementary for detecting METex14, LBx may preferentially select pts with a poorer prognosis and higher tumor load. Undetectable METex14 in baseline ctDNA may define a more favorable treatment outcome. Differences in populations identified by TBx and LBx should be considered when interpreting trial data. Table: 1382P

CI, confidence interval; DOR, duration of response; m, median; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.

Clinical trial identification

NCT02864992.

Editorial acknowledgement

Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) was provided by Mark Dyson, DPhil (Berlin, Germany) on behalf of Syneos Health, London, UK.

Legal entity responsible for the study

Merck Healthcare KGaA, Darmstadt, Germany.

Funding

Merck Healthcare KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

Disclosure

C.D. Rolfo: Financial Interests, Personal, Research Grant: Pfizer, Merck Sharpe & Dohme; Financial Interests, Personal, Other, consulting fees: Archer, Inivata, Bristol Myers Squibb, Novartis, Boston Pharmaceuticals, EMD Serono, an affiliate of Merck KGaA; Financial Interests, Personal, Other support: AstraZeneca, Roche, Guardant Health, Merck Sharpe & Dohme; Financial Interests, Personal, Other, safety monitoring board: EMD Serono, an affiliate of Merck KGaA; Financial Interests, Personal, Other, Leadership: International Society of Liquid Biopsy (ISLB), International Association for the Study of Lung Cancer (IASLC), European Society for Medical Oncology (ESMO). A.M. OBrate Grupp, C. Menzel, D. Juraeva, C. Stroh: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. R. Bruns: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Stocks/Shares: Merck Healthcare KGaA, Darmstadt, Germany. A. Johne: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Stocks/Shares: Novartis. P.K. Paik: Financial Interests, Personal, Advisory Role: Takeda, Xencor, CrownBio, Bicara, Mirati, EMD Serono, an affiliate of Merck KGaA; Financial Interests, Institutional, Research Grant: Bicara, Calithera, EMD Serono, an affiliate of Merck KGaA.