Abstract 1382P
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
Treatment-naive | Previously treated | |||
T+/L– (n=52) | T+/L+ (n=42) | T+/L– (n=54) | T+/L+ (n=32) | |
ORR, % (95% CI) | 57.7 (43.2, 71.3) | 64.3 (48.0, 78.4) | 44.4 (30.9, 58.6) | 53.1 (34.7, 70.9) |
mDOR, months (95% CI) | ne (10.4, ne) | 19.4 (7.6, ne) | 12.6 (5.1, 20.8) | 9.9 (4.4, 15.4) |
mPFS, months (95% CI) | 22.1 (14.8, ne) | 12.1 (7.8, 49.7) | 13.8 (8.2, 24.9) | 8.2 (5.5, 13.7) |
mOS, months (95% CI) | 32.7 (15.3, ne) | 28.5 (14.2, ne) | 20.8 (15.6, 32.5) | 19.8 (10.0, 26.5) |
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.
Resources from the same session
1391P - Capmatinib vs docetaxel as second- or third-line (2/3L) therapy in patients (pts) with METex14-mutated advanced NSCLC (aNSCLC): The GeoMETry-III trial
Presenter: Oscar Jose Juan Vidal
Session: Poster session 20
1392P - Safety and efficacy of crizotinib in MET mutated (METmut) advanced non-small cell lung Cancer (aNSCLC): Results from the Drug Rediscovery Protocol (DRUP)
Presenter: Karlijn Verkerk
Session: Poster session 20
1393P - Characteristics of MET gene and its relationship with TMB/MMR genes in Chinese NSCLC population
Presenter: Hong Yi Zhang
Session: Poster session 20
1394P - Real-world experience in treatment of patients with non-small cell lung cancer with BRAF and cMET Exon 14 skipping mutations
Presenter: Urska Janzic
Session: Poster session 20
1396P - HER2 testing pattern, characteristics of locally advanced or metastatic NSCLC patients by HER2 testing in France
Presenter: Didier Debieuvre
Session: Poster session 20
1397P - Prevalence, molecular characterization, and prognosis of MET–overexpressing non-small cell lung cancer (NSCLC) in a real-world patient cohort
Presenter: Jair Bar
Session: Poster session 20
1398P - Hepatotoxicity in patients (pts) with KRASG12C-mutated non-small cell lung cancer (NSCLC) treated with sotorasib after prior immunotherapy (IO)
Presenter: Sophie Ernst
Session: Poster session 20
1399P - Tumor-immune microenvironment analysis of de novo and acquired KRAS-mutated non-small cell lung cancer
Presenter: Joshua Reuss
Session: Poster session 20
1400P - Real-world effectiveness and safety of sotorasib in patients with KRAS G12C mutated metastatic non-small cell lung cancer (NSCLC): Results of the IFCT-2102 Lung KG12Ci study
Presenter: Marie Wislez
Session: Poster session 20
1401P - Impact of KRAS mutation on non-small cell lung cancer survival outcomes
Presenter: Quentin Thomas
Session: Poster session 20