Citations 2
Retreatment with First-Generation Selective RET Inhibitors in RET -Rearranged NSCLC Pretreated with Selpercatinib or Pralsetinib: Results from the RET-MAP Registry
Marinello, A., Rotow, Julia K., Lomibao, Meghanne , Miliziano, Daniela , Leporati, Rita , Feng, Jamie , Metro, Giulio , Brandão, Mariana , Gorría, Teresa , Nassar, Amin H. , Fila, Matteo, Fallet, V., Ricciuti, Biagio, Taylor, Skyler, Remon, Jordi, Planchard, David, Florez, Narjust, Besse, Benjamin, Drilon, Alexander D., Aldea, Mihaela, Nassar, Amin H. , Rotow, Julia , Metro, Giulio , Marinello, Arianna , Marinello, Arianna , Rotow, Julia K. , Citarella, Fabrizio , Fila, Matteo , Fallet, Vincent , Ricciuti, Biagio , Taylor, Skyler , Remon, Jordi , Planchard, David , Duma, Narjust , Besse, Benjamin , Drilon, Alexander , Aldea, Mihaela , Feng, Jamie , Citarella, Fabrizio , Ricciuti, Biagio , Planchard, David , Florez, Narjust , Besse, Benjamin , Aldea, Mihaela
Clinical Cancer Research | April 7, 2026 | Volume: 32 | Issue: 13 | Pages: 2637-2643
Abstract Purpose: In RET-rearranged non–small cell lung cancer (NSCLC), treatment options after first-generation selective RET inhibitors (SRI) are limited, and the value of SRI retreatment remains unclear. This study evaluates outcomes of SRI retreatment. Experimental Design: This multicenter retrospective study included patients with advanced RET-rearranged NSCLC who received ≥2 SRI-based therapy lines. Of 411 SRI-treated patients, 41 (10%) underwent SRI retreatment. Outcomes included objective response rate (ORR), progression-free survival (PFS), 6-month PFS, time to treatment failure, adverse events (AE). Results: Among 41 patients, 14 (34%) discontinued the initial SRI because of toxicity and 27 (66%) because of progression. After discontinuation for toxicity, all switched to an alternate SRI, achieving an ORR of 67%, median PFS of 9.9 months, and 6-month PFS of 80.3%. AEs reoccurred in nine patients (64%), with grade ≥3 AEs in 3 (21%) who switched at full dose. Among patients who discontinued because of progression, SRI monotherapy (n = 13) achieved an ORR of 23%, median PFS of 7 months, and 6-month PFS of 61.5%. Benefit was observed in patients with brain-only or oligoprogressive disease or dose reduction on first SRI. Combination therapy (n = 14; targeted agents, n = 11; chemotherapy, n = 3) achieved an ORR of 39%, median PFS of 4 months, and 6-month PFS of 27.3%. Conclusions: Same-class SRI switch after toxicity is feasible and clinically active but warrants cautious, dose-adjusted switching to mitigate toxicities. The efficacy of SRI rechallenge after progression seems limited overall. However, selected patients, such as those with brain-only or oligoprogressive disease, may derive benefit.
Antitumor Activity of Vebreltinib and Characterization of Clinicogenomic Features in Solid Tumors with MET Rearrangements
Nakazawa, Seshiru , Pecci, Federica , Odintsov, Igor , Gazgalis, Dimitris , Gottlieb, Felix H. , Ricciuti, Biagio , Zullo, Lodovica , Alessi, Joao V. , Federico, Alessandro Di , Aldea, Mihaela , Garbo, Edoardo , Saini, Arushi , Jiang, Jie , Baldacci, Simon , Makarem, Maisam , Locquet, Marie-Anaïs , Haradon, Danielle , Italiano, Antoîne , Lavaud, Pernelle , Vasseur, Damien , Planchard, David , Watanabe, Y., Mahran, Hoda A., Niu, Jiaxin , Swan, Leong Swan, Tay, Kevin , Kizilbash, Sani H. , Yu, Kin-Hung P. , Zhang, Xiaoling , Chen, Pan , Sangem, Mythili, Che, Jianwei , Sholl, Lynette M. , Jänne, Pasi A. , Di Federico, Alessandro , Gandhi, Malini M , Saini, Arushi , Feng, William W , Jiang, Jie , Baldacci, Simon , Facchinetti, Francesco , Makarem, Maisam , Locquet, Marie-Anaïs , Haratani, Koji , Haradon, Danielle , Besse, Benjamin , Italiano, Antoine , Remon, Jordi , Lavaud, Pernelle , Vasseur, Damien , Planchard, David , Sato, Yusuke , Watanabe, Yukako , Owen, Scott , Cortot, Alexis B , Mahran, Hoda , Forster, Martin D , Niu, Jiaxin , Tomasini, Pascale , Leong, Swan Swan , Tay, Kevin , Esteban, Emilio , Minchom, Anna , Kizilbash, Sani H , Cruz-Correa, Marcia , Yu, Kin-Hung Peony , Zhang, Xiaoling , Chen, Pan , Sangem, Mythili , Che, Jianwei , Sholl, Lynette , Jänne, Pasi A , Awad, Mark M , Odintsov, Igor , Ricciuti, Biagio , Aldea, Mihaela , Garbo, Edoardo , Gazgalis, Dimitris , Besse, Benjamin , Cortot, Alexis B. , Tomasini, Pascale , Cruz‐Correa, Marcia , Awad, Mark M.
Cancer Discovery | April 9, 2025 | Volume: 15 | Issue: 6 | Pages: 1129-1140
Abstract Oncogenic translocations involving the MET gene have been reported in several cancer types, but detailed clinicogenomic characterization of these cancers is not well defined. In addition, prospective clinical trials evaluating the antitumor activity of MET inhibitors in MET rearrangement–positive cancers are limited. In this study, in a pan-cancer analysis of >46,000 solid tumors with comprehensive genomic profiling, we identified oncogenic MET rearrangements in ∼0.04% of cancers. Preliminary analysis from a phase II clinical trial of the type I MET tyrosine kinase inhibitor (TKI) vebreltinib in MET fusion–positive solid tumors demonstrated an objective response rate of 50% and disease control rate of 79%, with antitumor activity seen in diverse cancer types, including lung adenocarcinoma and intrahepatic cholangiocarcinoma, among others. Similar to MET exon 14–altered lung cancer, secondary mutations in the kinase domain can confer resistance to MET TKIs in MET fusion–positive cancers. Overall, these data categorize MET rearrangements as actionable targets in solid tumors. Significance: MET rearrangement–positive cancers are not well-characterized, and optimal treatment strategies are yet to be defined. Through comprehensive genomic analysis, preclinical modeling, and preliminary results of a phase II clinical trial, we demonstrate that MET fusions are a unique molecular subtype of cancers targetable with vebreltinib, a TKI in development.