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1. Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial

Author

Wu, Yi-Long, Guarneri, Valentina, Voon, Pei Jye, Lim, Boon Khaw, Yang, Jin-Ji, Wislez, Marie, Huang, Cheng, Liam, Chong Kin, Mazieres, Julien, Tho, Lye Mun, Hayashi, Hidetoshi, Nhung, Nguyen Viet, Chia, Puey Ling, de Marinis, Filippo, Raskin, Jo, Zhou, Qinghua, Finocchiaro, Giovanna, Le, Anh Tuan, Wang, Jialei, Dooms, Christophe, Kato, Terufumi, Nadal, Ernest, Hin, How Soon, Smit, Egbert F, Wermke, Martin, Tan, Daniel, Morise, Masahiro, O'Brate, Aurora, Adrian, Svenja, Pfeiffer, Boris M, Stroh, Christopher, Juraeva, Dilafruz, Strotmann, Rainer, Goteti, Kosalaram, Berghoff, Karin, Ellers-Lenz, Barbara, Karachaliou, Niki, Le, Xiuning, and Kim, Tae Min

Published
2024
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8. Landscape and Clonal Dominance of Co-occurring Genomic Alterations in Non–Small-Cell Lung Cancer Harboring MET Exon 14 Skipping

Author

Le, Xiuning, Hong, Lingzhi, Hensel, Chuck, Chen, Rongrong, Kemp, Haley, Coleman, Niamh, Ciunci, Christine A., Liu, Stephen V., Negrao, Marcelo V., Yen, Jennifer, Xia, Xuefeng, Scheuenpflug, Juergen, Stroh, Christopher, Juraeva, Dilafruz, Tsao, Anne, Hong, David, Raymond, Victoria, Paik, Paul, Zhang, Jianjun, and Heymach, John V.

Published
2021
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12. Supplementary Table 1 from Targeting the MET Receptor Tyrosine Kinase as a Strategy for Radiosensitization in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

Author

Nisa, Lluís, primary, Francica, Paola, primary, Giger, Roland, primary, Medo, Matúš, primary, Elicin, Olgun, primary, Friese-Hamim, Manja, primary, Wilm, Claudia, primary, Stroh, Christopher, primary, Bojaxhiu, Beat, primary, Quintin, Aurélie, primary, Caversaccio, Marco D., primary, Dettmer, Matthias S., primary, Buchwalder, Mélanie, primary, Brodie, Tess M., primary, Aebersold, Daniel M., primary, Zimmer, Yitzhak, primary, Carey, Thomas E., primary, and Medová, Michaela, primary

Published
2023
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13. Data from Targeting the MET Receptor Tyrosine Kinase as a Strategy for Radiosensitization in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

Author

Nisa, Lluís, primary, Francica, Paola, primary, Giger, Roland, primary, Medo, Matúš, primary, Elicin, Olgun, primary, Friese-Hamim, Manja, primary, Wilm, Claudia, primary, Stroh, Christopher, primary, Bojaxhiu, Beat, primary, Quintin, Aurélie, primary, Caversaccio, Marco D., primary, Dettmer, Matthias S., primary, Buchwalder, Mélanie, primary, Brodie, Tess M., primary, Aebersold, Daniel M., primary, Zimmer, Yitzhak, primary, Carey, Thomas E., primary, and Medová, Michaela, primary

Published
2023
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14. Supplementary figures 1-6 from Targeting the MET Receptor Tyrosine Kinase as a Strategy for Radiosensitization in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

Author

Nisa, Lluís, primary, Francica, Paola, primary, Giger, Roland, primary, Medo, Matúš, primary, Elicin, Olgun, primary, Friese-Hamim, Manja, primary, Wilm, Claudia, primary, Stroh, Christopher, primary, Bojaxhiu, Beat, primary, Quintin, Aurélie, primary, Caversaccio, Marco D., primary, Dettmer, Matthias S., primary, Buchwalder, Mélanie, primary, Brodie, Tess M., primary, Aebersold, Daniel M., primary, Zimmer, Yitzhak, primary, Carey, Thomas E., primary, and Medová, Michaela, primary

Published
2023
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15. Supplementary Methods from Targeting the MET Receptor Tyrosine Kinase as a Strategy for Radiosensitization in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

Author

Nisa, Lluís, primary, Francica, Paola, primary, Giger, Roland, primary, Medo, Matúš, primary, Elicin, Olgun, primary, Friese-Hamim, Manja, primary, Wilm, Claudia, primary, Stroh, Christopher, primary, Bojaxhiu, Beat, primary, Quintin, Aurélie, primary, Caversaccio, Marco D., primary, Dettmer, Matthias S., primary, Buchwalder, Mélanie, primary, Brodie, Tess M., primary, Aebersold, Daniel M., primary, Zimmer, Yitzhak, primary, Carey, Thomas E., primary, and Medová, Michaela, primary

Published
2023
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16. Supplementary Table 2 from Targeting the MET Receptor Tyrosine Kinase as a Strategy for Radiosensitization in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

Author

Nisa, Lluís, primary, Francica, Paola, primary, Giger, Roland, primary, Medo, Matúš, primary, Elicin, Olgun, primary, Friese-Hamim, Manja, primary, Wilm, Claudia, primary, Stroh, Christopher, primary, Bojaxhiu, Beat, primary, Quintin, Aurélie, primary, Caversaccio, Marco D., primary, Dettmer, Matthias S., primary, Buchwalder, Mélanie, primary, Brodie, Tess M., primary, Aebersold, Daniel M., primary, Zimmer, Yitzhak, primary, Carey, Thomas E., primary, and Medová, Michaela, primary

Published
2023
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20. Abstract 1106: Detection of MET alterations at the DNA, RNA and protein levels in NSCLC patients progressing on ALK and ROS1 targeted therapies

Author

Jordana-Ariza, Núria, primary, Reischmann, Nadine, additional, Esparré, Carlos, additional, Román, Ruth, additional, Aguado-Esteban, Cristina, additional, García-Román, Silvia, additional, Stroh, Christopher, additional, Aguilar, Andrés Aguilar, additional, Rosell, Rafael, additional, Karachaliou, Niki, additional, and Molina-Vila, Miguel A., additional

Published
2022
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21. Abstract 1105: MET or SHP2 inhibition enhances targeted therapies and delays the emergence of resistance in oncogene-driven NSCLC

Author

Reischmann, Nadine, primary, Pudelko, Lorenz, additional, Stroh, Christopher, additional, Linde, Nina, additional, Musch, Doreen, additional, Keil, Marina, additional, Pudelko, Linda, additional, Esdar, Christina, additional, Blaukat, Andree, additional, Schumacher, Karl M., additional, and Karachaliou, Niki, additional

Published
2022
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23. Clinical response to tepotinib according to circulating tumor (ct) DNA biomarkers in patients with advanced NSCLC with high-level MET amplification (METamp) detected by liquid biopsy (LBx).

Author

Le, Xiuning, primary, Paz-Ares, Luis, additional, Van Meerbeeck, Jan, additional, Viteri Ramirez, Santiago, additional, Cabrera Galvez, Carlos, additional, Vicente Baz, David, additional, Kim, Young-Chul, additional, Kang, Jin-Hyoung, additional, Stroh, Christopher, additional, Juraeva, Dilafruz, additional, Bruns, Rolf, additional, Otto, Gordon, additional, Johne, Andreas, additional, and Paik, Paul K., additional

Published
2022
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26. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer

Author

Van Cutsem, Eric, Kohne, Claus-Henning, Hitre, Erika, Zaluski, Jerzy, Chien, Chung-Rong Chang, Makhson, Anatoly, D'Haens, Geert, Pinter, Tamas, Lim, Robert, Bodoky, Gyorgy, Roh, Jae Kyung, Folprecht, Gunnar, Ruff, Paul, Stroh, Christopher, Tejpar, Sabine, Schlichting, Michael, Nippgen, Johannes, and Rougier, Philippe

Subjects
Fluorouracil -- Usage, Fluorouracil -- Health aspects, Leucovorin -- Usage, Leucovorin -- Health aspects, Colorectal cancer -- Care and treatment
Abstract

A study was conducted to evaluate the efficacy of the use of cetuximab and irinotecan, fluorouracil and leucovorin (FOLFIRI) as a first-line of treatment for metastatic colorectal cancer. Results indicated that a combination of cetuximab with FOLFIRI was more effective in reducing the progress of the cancer as compared to FOLFIRI alone.

Published
2009

27. METex14 ctDNA dynamics & resistance mechanisms detected in liquid biopsy (LBx) from patients (pts) with METex14 skipping NSCLC treated with tepotinib.

Author

Paik, Paul K., primary, Veillon, Remi, additional, Felip, Enriqueta, additional, Cortot, Alexis, additional, Sakai, Hiroshi, additional, Mazieres, Julien, additional, Thomas, Michael, additional, Reinmuth, Niels, additional, Raskin, Jo, additional, Conte, Pier Franco, additional, Garassino, Marina Chiara, additional, Iams, Wade Thomas, additional, Griesinger, Frank, additional, Kowalski, Dariusz M., additional, Stroh, Christopher, additional, Juraeva, Dilafruz, additional, Scheuenpflug, Juergen, additional, Johne, Andreas, additional, and Le, Xiuning, additional

Published
2021
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29. Cetuximab-mediated protection from hypoxia-induced cell death: implications for therapy sequence in colorectal cancer

Author

Urban, Hans, Maurer, Gabriele Dorothea, Luger, Anna-Luisa, Lorenz, Nadja I., Sauer, Benedikt, Stroh, Christopher, Trojan, Jörg, Mittelbronn, Michel, Steinbach, Joachim Peter, Harter, Patrick Nikolaus, and Ronellenfitsch, Michael Wilfried

Subjects
ddc:610, neoplasms, digestive system diseases
Abstract

Simple Summary: Therapeutic antibodies are an integral part of treatment regimens for metastasized colorectal cancer. In KRAS wildtype tumors both bevacizumab and cetuximab are active. While bevacizumab has previously been shown to induce tumor hypoxia, we here report that EGFR inhibition by cetuximab protects colon cancer cells from hypoxia-induced cell death. This effect appears to be responsible for the inferior efficacy of a treatment sequence of bevacizumab followed by cetuximab versus an inverse sequence that we observed in a colorectal cancer mouse model. It also offers a mechanistic explanation for effects observed in clinical trials such as underadditive or even detrimental effects when combining bevacizumab and cetuximab (CAIRO2 trial) and the superior efficacy of first line cetuximab (FIRE-3 trial) under chemotherapy backbones in colorectal cancer. Abstract: Monoclonal antibodies like cetuximab, targeting the epidermal growth factor receptor (EGFR), and bevacizumab, targeting the vascular endothelial growth factor (VEGF), are an integral part of treatment regimens for metastasized colorectal cancer. However, inhibition of the EGFR has been shown to protect human glioma cells from cell death under hypoxic conditions. In colon carcinoma cells, the consequences of EGFR blockade in hypoxia (e.g., induced by bevacizumab) have not been evaluated yet. LIM1215 and SW948 colon carcinoma and LNT-229 glioblastoma cells were treated with cetuximab, PD153035, and erlotinib and analyzed for cell density and viability. The sequential administration of either cetuximab followed by bevacizumab (CET->BEV) or bevacizumab followed by cetuximab (BEV->CET) was investigated in a LIM1215 (KRAS wildtype) and SW948 (KRAS mutant) xenograft mouse model. In vitro, cetuximab protected from hypoxia. In the LIM1215 model, a survival benefit with cetuximab and bevacizumab monotherapy was observed, but only the sequence CET->BEV showed an additional benefit. This effect was confirmed in the SW948 model. Our observations support the hypothesis that bevacizumab modulates the tumor microenvironment (e.g., by inducing hypoxia) where cetuximab could trigger protective effects when administered later on. The sequence CET->BEV therefore seems to be superior as possible mutual adverse effects are bypassed.

Published
2020

30. Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations

Author

Paik, Paul K., Felip, Enriqueta, Veillon, Remi, Sakai, Hiroshi, Cortot, Alexis B., Garassino, Marina C., Mazieres, Julien, Viteri, Santiago, Senellart, Helene, van Meerbeeck, Jan, Raskin, Jo, Reinmuth, Niels, Conte, Pierfranco, Kowalski, Dariusz, Cho, Byoung Chul, Patel, Jyoti D., Horn, Leora, Griesinger, Frank, Han, Ji-Youn, Kim, Young-Chul, Chang, Gee-Chen, Tsai, Chen-Liang, Yang, James C. -H., Chen, Yuh-Min, Smit, Egbert F., van der Wekken, Anthonie J., Kato, Terufumi, Juraeva, Dilafruz, Stroh, Christopher, Bruns, Rolf, Straub, Josef, Johne, Andreas, Scheele, Juergen, Heymach, John V., Le, Xiuning, and Damage and Repair in Cancer Development and Cancer Treatment (DARE)

Subjects
Adult, Male, Lung Neoplasms, Antineoplastic Agents, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, Exon, 0302 clinical medicine, Piperidines, Transcription (biology), Carcinoma, Non-Small-Cell Lung, medicine, Carcinoma, Edema, Humans, 030212 general & internal medicine, Lung cancer, Protein Kinase Inhibitors, Aged, Aged, 80 and over, business.industry, General Medicine, Exons, Middle Aged, Proto-Oncogene Proteins c-met, medicine.disease, MET Exon 14 Skipping Mutation, respiratory tract diseases, Pyridazines, Pyrimidines, Multicenter study, Mutation, Cancer research, Female, Non small cell, Human medicine, business
Abstract

BACKGROUND A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driverMEToccurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population. METHODS In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmedMETexon 14 skipping mutation. The primary end point was the objective response by independent review among patients who had undergone at least 9 months of follow-up. The response was also analyzed according to whether the presence of aMETexon 14 skipping mutation was detected on liquid biopsy or tissue biopsy. RESULTS As of January 1, 2020, a total of 152 patients had received tepotinib, and 99 patients had been followed for at least 9 months. The response rate by independent review was 46% (95% confidence interval [CI], 36 to 57), with a median duration of response of 11.1 months (95% CI, 7.2 to could not be estimated) in the combined-biopsy group. The response rate was 48% (95% CI, 36 to 61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37 to 63) among 60 patients in the tissue-biopsy group; 27 patients had positive results according to both methods. The investigator-assessed response rate was 56% (95% CI, 45 to 66) and was similar regardless of the previous therapy received for advanced or metastatic disease. Adverse events of grade 3 or higher that were considered by investigators to be related to tepotinib therapy were reported in 28% of the patients, including peripheral edema in 7%. Adverse events led to permanent discontinuation of tepotinib in 11% of the patients. A molecular response, as measured in circulating free DNA, was observed in 67% of the patients with matched liquid-biopsy samples at baseline and during treatment. CONCLUSIONS Among patients with advanced NSCLC with a confirmedMETexon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients.Peripheral edema was the main toxic effect of grade 3 or higher. Abstract: BACKGROUND A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driverMEToccurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population. METHODS In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmedMETexon 14 skipping mutation. The primary end point was the objective response by independent review among patients who had undergone at least 9 months of follow-up. The response was also analyzed according to whether the presence of aMETexon 14 skipping mutation was detected on liquid biopsy or tissue biopsy. RESULTS As of January 1, 2020, a total of 152 patients had received tepotinib, and 99 patients had been followed for at least 9 months. The response rate by independent review was 46% (95% confidence interval [CI], 36 to 57), with a median duration of response of 11.1 months (95% CI, 7.2 to could not be estimated) in the combined-biopsy group. The response rate was 48% (95% CI, 36 to 61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37 to 63) among 60 patients in the tissue-biopsy group; 27 patients had positive results according to both methods. The investigator-assessed response rate was 56% (95% CI, 45 to 66) and was similar regardless of the previous therapy received for advanced or metastatic disease. Adverse events of grade 3 or higher that were considered by investigators to be related to tepotinib therapy were reported in 28% of the patients, including peripheral edema in 7%. Adverse events led to permanent discontinuation of tepotinib in 11% of the patients. A molecular response, as measured in circulating free DNA, was observed in 67% of the patients with matched liquid-biopsy samples at baseline and during treatment. CONCLUSIONS Among patients with advanced NSCLC with a confirmedMETexon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients.Peripheral edema was the main toxic effect of grade 3 or higher.

Published
2020

33. Activity of tepotinib in hepatocellular carcinoma (HCC) with high-level MET amplification (METamp): Preclinical and clinical evidence.

Author

Faivre, Sandrine J., primary, Blanc, Jean-frederic, additional, Pan, Hongming, additional, Grando, Véronique, additional, Lim, Ho Yeong, additional, Cubillo Gracián, Antonio, additional, Isambert, Nicolas, additional, Johne, Andreas, additional, Schumacher, Karl, additional, Stroh, Christopher, additional, Friese-Hamim, Manja, additional, O'Brate, Aurora, additional, Zhou, Dongli, additional, and Qin, Shukui, additional

Published
2021
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34. Cetuximab-Mediated Protection from Hypoxia- Induced Cell Death: Implications for Therapy Sequence in Colorectal Cancer

Author

Urban, Hans, primary, Maurer, Gabriele D., additional, Luger, Anna-Luisa, additional, Lorenz, Nadja I., additional, Sauer, Benedikt, additional, Stroh, Christopher, additional, Trojan, Jörg, additional, Mittelbronn, Michel, additional, Steinbach, Joachim P., additional, Harter, Patrick N., additional, and Ronellenfitsch, Michael W., additional

Published
2020
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36. Abstract 3385: Liquid biopsy to detect MET exon 14 skipping (METex14) and MET amplification in patients with advanced NSCLC: Biomarker analysis from VISION study

Author

Le, Xiuning, primary, Kowalski, Dariusz, additional, Cho, Byoung Chul, additional, Conte, Pierfranco, additional, Felip, Enriqueta, additional, Garassino, Marina Chiara, additional, Viteri, Santiago, additional, Chang, Gee-Chen, additional, Richart, John, additional, Paz-Ares, Luiz, additional, Juraeva, Dilafruz, additional, Straub, Josef, additional, Stroh, Christopher, additional, and Paik, Paul, additional

Published
2020
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37. Abstract 3407: Anti-tumor activity of tepotinib in orthotopic models of lung cancer patient-derived brain metastases with MET amplification

Author

Friese-Hamim, Manja, primary, Clark, Anderson, additional, Crowley, Lindsey, additional, Reusch, Christof, additional, Bogatyrova, Olga, additional, Wilm, Claudia, additional, Zhang, Hong, additional, Crandall, Timothy, additional, Lin, Jing, additional, Ma, Jianguo, additional, Bachner, David, additional, Schmidt, Jürgen, additional, Schaefer, Martin, additional, and Stroh, Christopher, additional

Published
2020
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38. Targeting the MET Receptor Tyrosine Kinase as a Strategy for Radiosensitization in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

Author

Nisa, Lluís, primary, Francica, Paola, additional, Giger, Roland, additional, Medo, Matúš, additional, Elicin, Olgun, additional, Friese-Hamim, Manja, additional, Wilm, Claudia, additional, Stroh, Christopher, additional, Bojaxhiu, Beat, additional, Quintin, Aurélie, additional, Caversaccio, Marco D., additional, Dettmer, Matthias S., additional, Buchwalder, Mélanie, additional, Brodie, Tess M., additional, Aebersold, Daniel M., additional, Zimmer, Yitzhak, additional, Carey, Thomas E., additional, and Medová, Michaela, additional

Published
2020
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40. Targeting the MET receptor tyrosine kinase as a strategy for radiosensitization in loco-regionally advanced head and neck squamous cell carcinoma

Author

Nisa, Lluís, Francica, Paola, Giger, Roland, Medo, Matúš, Eliçin, Olgun, Friese-Hamim, Manja, Wilm, Claudia, Stroh, Christopher, Bojaxhiu, Beat, Quintin, Aurélie, Caversaccio, Marco D., Dettmer, Matthias S., Buchwalder, Mélanie, Brodie, Tess M., Aebersold, Daniel M., Zimmer, Yitzhak, Carey, Thomas E., and Medova, Michaela

Subjects
570 Life sciences, biology, 610 Medicine & health
Published
2020
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42. ctDNA Dynamics, Prognostic Markers, and Mechanisms of Resistance in Tepotinib-treated MET exon 14 (METex14) Skipping NSCLC in the VISION Trial.

Author

Xiuning Le, Garassino, Marina Chiara, Myung-Ju Ahn, Felip, Enriqueta, Cortot, Alexis B., Hiroshi Sakai, Mazières, Julien, Thomas, Michael, Viteri, Santiago, Conte, Pierfranco, Chih-Hsin Yang, James, Iams, Wade Thomas, Griesinger, Frank, Braggio, Danielle, Stroh, Christopher, Juraeva, Dilafruz, Wang, Danyi, Johne, Andreas, and Paik, Paul K.

Subjects
NUCLEIC acid analysis, EVALUATION of medical care, LUNG cancer, ONCOLOGY nursing, DNA, CONFERENCES & conventions, NURSES, EXTRACELLULAR space, TUMOR markers, BODY fluid examination
Abstract

Background: Oncology nurse navigators are integral members of multidisciplinary teams that manage patients with non--small cell lung cancer (NSCLC), including the 3%-4% of patients with mesenchymal-epithelial transition exon 14 (METex14) skipping mutation. This oncogenic driver confers a poor prognosis but sensitizes tumors to MET inhibitors. Tepotinib, an oral, selective MET inhibitor, showed robust, durable efficacy in METex14 NSCLC in the VISION trial. Objective: To support nurse navigators and other professionals managing these patients, we conducted an exploratory analysis of VISION to evaluate circulating tumor DNA (ctDNA) and MET-related biomarkers in liquid biopsy (LBx [ie, blood]) samples and their associations with clinical outcomes. Methods: Baseline, on-treatment and/or end-of-treatment (EOT) LBx from VISION were analyzed by ctDNA next-generation sequencing (NGS; Guardant360®) and enzyme-linked immunoassay for shed MET (sMET; a soluble form of the MET extracellular domain) and hepatocyte growth factor (HGF; the ligand for MET). Patients with baseline LBx NGS profiles (n=165) were classified as positive (L+) or negative (L-) for METex14 (all L- patients had METex14 by tissue NGS). On-treatment response was analyzed in L+ patients with 2 consecutive on-treatment samples (n=81). Confirmed molecular response (cMR) was defined as >75% depletion from baseline in METex14 variant allele frequency (VAF) in 2 consecutive on-treatment samples; molecular progression (MP) was defined as VAF increase from baseline in ≥1 on-treatment sample. Objective response rate (ORR), median duration of response (mDOR), median progression-free survival (mPFS), and median overall survival (mOS) were evaluated according to biomarker status. Mechanisms of acquired resistance were investigated in postprogression EOT samples. Data cut-off date was November 20, 2022. Results: Patients with high (>upper quartile, n=58) versus low (≤upper quartile, n=175) baseline HGF had numerically shorter mDOR and mPFS. Patients with low (≤lower quartile, n=61) versus high (>lower quartile, n=183) relative change in sMET from baseline had numerically higher ORR, mPFS, and mOS. In L- (n=51) versus L+ (n=114) patients, ORR was comparable, but mDOR and mPFS were longer. Seven of 10 patients with MET amplification, 1 of 5 patients with KRAS/NRAS mutation, 1 of 5 patients with PI3K/AKT pathway alterations, and 0 of 2 patients with EGFR mutations at baseline had objective response. Patients with tumor protein 53 (TP53) mutations (73/165) versus wild-type had comparable ORR but shorter mPFS (8.2 vs 11.3 mo, respectively). Patients with cMR (n=65 [80%]) versus MP (n=12 [15%]) had better outcomes (ORR: 63.1% vs 16.7%, respectively; mDOR: 18.5 vs 6.2 mo, respectively; mPFS: 11.2 vs 4.2 mo, respectively). At EOT, 9 of 73 patients (12%) had acquired MET kinase domain mutations and 9 of 73 (12%) had emerging alterations in KRAS, EGFR, MYC, BRAF, RB1, and ERBB2. Conclusions: In the largest on-treatment LBx biomarker dataset for an MET inhibitor in METex14 NSCLC, MR was associated with improved outcomes and TP53 mutation had negative prognostic significance. On-target secondary MET mutations and off-target bypass pathway activation were potential resistance mechanisms. These data can help to inform nurse navigators and other healthcare professionals managing patients receiving tepotinib for METex14 skipping NSCLC. [ABSTRACT FROM AUTHOR]

Published
2023

44. PPD01.01 ctDNA Dynamics, Prognostic Markers and Resistance Mechanisms in Tepotinib-treated METexon 14 (METex14) Skipping NSCLC in the VISION Trial

Author

Le, Xiuning, Garassino, Marina Chiara, Ahn, Myung-Ju, Felip, Enriqueta, Cortot, Alexis B., Sakai, Hiroshi, Mazières, Julien, Thomas, Michael, Viteri, Santiago, Conte, Pierfranco, Chih-Hsin Yang, James, Iams, Wade Thomas, Griesinger, Frank, O’Hara, Richard M., Stroh, Christopher, Juraeva, Dilafruz, Wang, Danyi, Johne, Andreas, and Paik, Paul K.

Published
2024
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46. Abstract 2149: The anti-EGFR antibody mixture Sym004 overcomes acquired resistance to cetuximab in colorectal cancer

Author

Sanchez-Martin, Francisco J., primary, Dalmases, Alba, additional, Bellosillo, Beatriz, additional, Argiles, Guillem, additional, Gelabert, Mariona, additional, Cañadas, Israel, additional, Vidal, Joana, additional, Siravegna, Giulia, additional, Arena, Sabrina, additional, Koefoed, Klaus, additional, Visa, Laura, additional, Arpí, Oriol, additional, Horak, Ivan D., additional, Iglesias, Mar, additional, Stroh, Christopher, additional, Kragh, Michael, additional, Rovira, Ana, additional, Albanell, Joan, additional, Bardelli, Alberto, additional, Tabernero, Josep, additional, and Montagut, Clara, additional

Published
2016
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47. The First-in-class Anti-EGFR Antibody Mixture Sym004 Overcomes Cetuximab Resistance Mediated by EGFR Extracellular Domain Mutations in Colorectal Cancer

Author

Sánchez-Martín, Francisco J., primary, Bellosillo, Beatriz, additional, Gelabert-Baldrich, Mariona, additional, Dalmases, Alba, additional, Cañadas, Israel, additional, Vidal, Joana, additional, Martinez, Alejandro, additional, Argilés, Guillem, additional, Siravegna, Giulia, additional, Arena, Sabrina, additional, Koefoed, Klaus, additional, Visa, Laura, additional, Arpí, Oriol, additional, Horak, Ivan David, additional, Iglesias, Mar, additional, Stroh, Christopher, additional, Kragh, Michael, additional, Rovira, Ana, additional, Albanell, Joan, additional, Tabernero, Josep, additional, Bardelli, Alberto, additional, and Montagut, Clara, additional

Published
2016
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48. Tepotinib in patients with non-small cell lung cancer with high-level METamplification detected by liquid biopsy: VISION Cohort B

Author

Le, Xiuning, Paz-Ares, Luis G., Van Meerbeeck, Jan, Viteri, Santiago, Galvez, Carlos Cabrera, Smit, Egbert F., Garassino, Marina, Veillon, Remi, Baz, David Vicente, Pradera, Jose Fuentes, Sereno, María, Kozuki, Toshiyuki, Kim, Young-Chul, Yoo, Seung Soo, Han, Ji-Youn, Kang, Jin-Hyoung, Son, Choon-Hee, Choi, Yoon Ji, Stroh, Christopher, Juraeva, Dilafruz, Vioix, Helene, Bruns, Rolf, Otto, Gordon, Johne, Andreas, and Paik, Paul K.

Abstract

High-level METamplification (METamp) is a primary driver in ∼1%–2% of non-small cell lung cancers (NSCLCs). Cohort B of the phase 2 VISION trial evaluates tepotinib, an oral MET inhibitor, in patients with advanced NSCLC with high-level METamp who were enrolled by liquid biopsy. While the study was halted before the enrollment of the planned 60 patients, the results of 24 enrolled patients are presented here. The objective response rate (ORR) is 41.7% (95% confidence interval [CI], 22.1–63.4), and the median duration of response is 14.3 months (95% CI, 2.8–not estimable). In exploratory biomarker analyses, focal METamp, RB1wild-type, MYCdiploidy, low circulating tumor DNA (ctDNA) burden at baseline, and early molecular response are associated with better outcomes. Adverse events include edema (composite term; any grade: 58.3%; grade 3: 12.5%) and constipation (any grade: 41.7%; grade 3: 4.2%). Tepotinib provides antitumor activity in high-level METamp NSCLC (ClinicalTrials.gov: NCT02864992).

Published
2023
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49. Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Treatment and RAS Mutations in Colorectal Cancer

Author

Van Cutsem, Eric, primary, Lenz, Heinz-Josef, additional, Köhne, Claus-Henning, additional, Heinemann, Volker, additional, Tejpar, Sabine, additional, Melezínek, Ivan, additional, Beier, Frank, additional, Stroh, Christopher, additional, Rougier, Philippe, additional, van Krieken, J. Han, additional, and Ciardiello, Fortunato, additional

Published
2015
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