{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:35:14Z","timestamp":1792802114942,"version":"4.5.0"},"reference-count":32,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"13","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets\n              <jats:italic>EGFR<\/jats:italic>\n              exon 20 insertion (ex20ins) mutations in non\u2013small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2, ClinicalTrials.gov identifier:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04129502\">NCT04129502<\/jats:ext-link>\n              ) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of\n              <jats:italic>EGFR<\/jats:italic>\n              ex20ins+ advanced\/metastatic NSCLC.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>\n              Patients with treatment-naive\n              <jats:italic>EGFR<\/jats:italic>\n              ex20ins+ locally advanced\/metastatic NSCLC were randomly assigned 1:1 to mobocertinib 160 mg once daily or pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by maintenance pemetrexed. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR), with planned interim analysis (IA) after approximately 70% of 227 expected PFS events.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              A total of 354 patients were randomly assigned (mobocertinib: n = 179; chemotherapy: n = 175). Baseline characteristics were balanced between arms. At IA (cutoff: April 4, 2023), the median PFS per BICR was 9.6 months in each treatment arm (hazard ratio [HR], 1.04 [95% CI, 0.77 to 1.39];\n              <jats:italic>P<\/jats:italic>\n              = .803). The primary end point crossed the prespecified futility boundary (HR &gt; 1). The confirmed objective response rate (95% CI) per BICR was 32% (26 to 40) with mobocertinib versus 30% (24 to 38) with chemotherapy; the median duration of response was 12.0 versus 8.4 months. Quality-of-life assessments indicated clinically meaningful delays in time to deterioration of lung cancer symptoms, cognitive function, and constipation with mobocertinib versus chemotherapy. Grade \u22653 adverse events in &gt;5% of patients (mobocertinib, chemotherapy) were diarrhea (20%, 1%), anemia (6%, 10%), increased lipase (6%, 0%), and decreased neutrophil count (1%, 7%).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              The EXCLAIM-2 trial did not meet its primary end point. The efficacy of mobocertinib was not superior to platinum-based chemotherapy for first-line treatment of patients with\n              <jats:italic>EGFR<\/jats:italic>\n              ex20ins+ advanced\/metastatic NSCLC.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/jco-24-01269","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T20:59:06Z","timestamp":1738184346000},"page":"1553-1563","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":34,"title":["First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With\n            <i>EGFR<\/i>\n            Exon 20 Insertion\u2013Positive Metastatic Non\u2013Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct04129502","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7821-4928","authenticated-orcid":false,"given":"Pasi A.","family":"J\u00e4nne","sequence":"first","affiliation":[{"name":"Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin-Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Lung Cancer Institute, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-270X","authenticated-orcid":false,"given":"Byoung Chul","family":"Cho","sequence":"additional","affiliation":[{"name":"Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1617-3294","authenticated-orcid":false,"given":"Juan","family":"Li","sequence":"additional","affiliation":[{"name":"Sichuan Cancer Hospital, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Hochmair","sequence":"additional","affiliation":[{"name":"Klinik Floridsdorf, Vienna Healthcare Group and Karl Landsteiner Institute for Lung Research and Pulmonary Oncology, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0412-7143","authenticated-orcid":false,"given":"Solange","family":"Peters","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5090-8189","authenticated-orcid":false,"given":"Benjamin","family":"Besse","sequence":"additional","affiliation":[{"name":"Gustave Roussy, Paris-Saclay University, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1738-0316","authenticated-orcid":false,"given":"Nick","family":"Pavlakis","sequence":"additional","affiliation":[{"name":"Genesis Care, North Shore Health Hub and Northern Clinical School, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3119-9334","authenticated-orcid":false,"given":"Joel W.","family":"Neal","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5853-1424","authenticated-orcid":false,"given":"Terufumi","family":"Kato","sequence":"additional","affiliation":[{"name":"Kanagawa Cancer Center, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3611-0258","authenticated-orcid":false,"given":"Yi-Long","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2479-2271","authenticated-orcid":false,"given":"Danny","family":"Nguyen","sequence":"additional","affiliation":[{"name":"City of Hope National Medical Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7448-2984","authenticated-orcid":false,"given":"Junjing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Statistics and Quantitative Sciences, Takeda Development Center Americas, Inc, Lexington, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9123-0690","authenticated-orcid":false,"given":"Jianchang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Statistics and Quantitative Sciences, Takeda Development Center Americas, Inc, Lexington, 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Presented at Annual Congress of the European Society for Medical Oncology Paris France September 9-13 2022","DOI":"10.1016\/j.annonc.2022.07.1115"},{"key":"e_1_3_10_19_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-2072"},{"key":"e_1_3_10_20_2","unstructured":"Exkivity [package insert]. Takeda Pharmaceuticals America Inc Lexington MA 2023"},{"key":"e_1_3_10_21_2","unstructured":"FDA grants accelerated approval to mobocertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations [press release]. U.S. Food & Drug Administration 2021. https:\/\/ecancer.org\/en\/news\/20939-fda-grants-accelerated-approval-to-mobocertinib-for-metastatic-non-small-cell-lung-cancer-with-egfr-exon-20-insertion-mutations"},{"key":"e_1_3_10_22_2","unstructured":"Takeda\u2019s EXKIVITY (mobocertinib) receives approval from the NMPA of China becoming the first and only therapy available for patients with EGFR exon20 insertion+ NSCLC [press release]. 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