{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T06:03:20Z","timestamp":1794204200532,"version":"4.8.0"},"reference-count":29,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Otolaryngol Head Neck Surg"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor treated locally with surgery and radiation therapy. Despite high recurrence and distant failure rates, there is no approved systemic therapy for recurrent\/metastatic disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate amivantamab, a dual-target epidermal growth factor receptor (EGFR)\u2013mesenchymal\u2013epithelial transition (MET) bispecific antibody, as a novel treatment in patients with advanced ACC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>Between October 2022 and January 2025, this single-arm, open-label, phase 2 nonrandomized clinical trial enrolled patients with recurrent\/metastatic ACC at 3 US academic centers. Patients received amivantamab until disease progression or unacceptable toxic effects. Participants were aged 18 years and older with confirmed recurrent\/metastatic ACC not amenable to curative-intent therapy, who had progression within 6 months of study enrollment. Participants had at least 1 site of measurable disease by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), an Eastern Cooperative Oncology Group performance status of 0 to 1, and adequate organ and marrow function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>Patients received intravenous amivantamab, 1050 mg, if weighing less than 80 kg, or 1400 mg if weighing 80 kg or more, weekly for 1 month, followed by day 1 and 15 dosing every 28 days thereafter until progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes<\/jats:title>\n                    <jats:p>Primary end point was best overall response rate (ORR) per RECIST 1.1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty-one patients enrolled; 18 were efficacy evaluable. The median age was 61 years (range, 36-76 years), and 14 individuals (67%) were male. Most primary sites were the major\/minor salivary glands (17 patients [81%]), and 13 (62%) had distant metastatic disease. Nine patients (43%) had no prior systemic treatment. Six patients (29%) had 2 or more lines of prior therapy. Of 18 evaluable patients, best ORR was 5.6% (95% CI, 0-27.6%), with 1 partial response (in a patient with type 1 ACC and a somatic\n                      <jats:italic>EGFR<\/jats:italic>\n                      variant). Twelve patients (66.7% [95% CI, 43.6%-83.9%]) achieved stable disease. Five patients (27.8% [95% CI, 12.2%-51.2%]) experienced disease progression, yielding a clinical benefit rate of 72.2% (95% CI, 48.8%-87.8%). Common treatment-related adverse events (TRAEs) included acneiform dermatitis (18 [86%]), infusion-related reaction (16 [76%]), and fatigue (15 [71%]); 3 patients (14%) experienced grade 3 TRAEs (acneiform dermatitis, mucositis, and elevated alkaline phosphatase).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>While the primary end point of best ORR was not met in this nonrandomized clinical trial, amivantamab was well tolerated, and most patients exhibited disease stabilization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\/study\/NCT05074940\">NCT05074940<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaoto.2025.5404","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T16:30:32Z","timestamp":1772123432000},"page":"376","source":"Crossref","is-referenced-by-count":2,"title":["Amivantamab for Recurrent or Metastatic Adenoid Cystic Carcinoma"],"prefix":"10.1001","volume":"152","author":[{"given":"Glenn J.","family":"Hanna","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Dana-Faber Cancer Institute, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga Y.","family":"Zamulko","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Punita","family":"Grover","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R.","family":"Adkins","sequence":"additional","affiliation":[{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Washington University School of Medicine, Alvin J. Siteman Cancer Center, and Barnes\u2013Jewish Hospital, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Oppelt","sequence":"additional","affiliation":[{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Washington University School of Medicine, Alvin J. Siteman Cancer Center, and Barnes\u2013Jewish Hospital, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey E.","family":"Romano","sequence":"additional","affiliation":[{"name":"University of Cincinnati Cancer Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Lehn","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey M.","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn A.","family":"Wikenheiser-Brokamp","sequence":"additional","affiliation":[{"name":"University of Cincinnati Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Lemmon","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison J.","family":"Forsythe","sequence":"additional","affiliation":[{"name":"University of Cincinnati Cancer Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey L.","family":"Allen","sequence":"additional","affiliation":[{"name":"University of Cincinnati Cancer Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Pan","sequence":"additional","affiliation":[{"name":"Biostatistics and Informatics Shared Resource, University of Cincinnati Cancer Center, Cincinnati, Ohio"},{"name":"Cancer Data Science Center, University of Cincinnati College of Medicine, Cincinnati, Ohio"},{"name":"Department of Biostatistics, Health Informatics and Data Sciences, University of Cincinnati College of Medicine, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shesh N.","family":"Rai","sequence":"additional","affiliation":[{"name":"Biostatistics and Informatics Shared Resource, University of Cincinnati Cancer Center, Cincinnati, Ohio"},{"name":"Cancer Data Science Center, University of Cincinnati College of Medicine, Cincinnati, Ohio"},{"name":"Department of Biostatistics, Health Informatics and Data Sciences, University of Cincinnati College of Medicine, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia","family":"El-Gamal","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trisha M.","family":"Wise-Draper","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"key":"ooi250099r1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2022.105945","article-title":"Current opinions on diagnosis and treatment of adenoid cystic carcinoma.","volume":"130","author":"Fang","year":"2022","journal-title":"Oral Oncol"},{"issue":"7","key":"ooi250099r2","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.oraloncology.2015.04.005","article-title":"Adenoid cystic carcinoma of the head and neck\u2014an update.","volume":"51","author":"Coca-Pelaz","year":"2015","journal-title":"Oral Oncol"},{"key":"ooi250099r3","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2020.104690","article-title":"Long-term outcomes and clinicogenomic correlates in recurrent, metastatic adenoid cystic carcinoma.","volume":"106","author":"Hanna","year":"2020","journal-title":"Oral Oncol"},{"issue":"18","key":"ooi250099r4","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1200\/JCO.18.01859","article-title":"Phase II study of lenvatinib in patients with progressive, recurrent or metastatic adenoid cystic carcinoma.","volume":"37","author":"Tchekmedyian","year":"2019","journal-title":"J Clin Oncol"},{"issue":"9","key":"ooi250099r5","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1002\/cncr.32754","article-title":"Patients with adenoid cystic carcinomas of the salivary glands treated with lenvatinib: activity and quality of life.","volume":"126","author":"Locati","year":"2020","journal-title":"Cancer"},{"issue":"10","key":"ooi250099r6","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.1093\/annonc\/mdw287","article-title":"A phase II study of axitinib (AG-013736) in patients with incurable adenoid cystic carcinoma.","volume":"27","author":"Ho","year":"2016","journal-title":"Ann Oncol"},{"issue":"19","key":"ooi250099r7","doi-asserted-by":"publisher","first-page":"5272","DOI":"10.1158\/1078-0432.CCR-21-1061","article-title":"Randomized phase II study of axitinib versus observation in patients with recurred or metastatic adenoid cystic carcinoma.","volume":"27","author":"Kang","year":"2021","journal-title":"Clin Cancer Res"},{"issue":"22","key":"ooi250099r8","doi-asserted-by":"publisher","first-page":"4555","DOI":"10.1158\/1078-0432.CCR-23-1030","article-title":"A phase II trial of rivoceranib, an oral vascular endothelial growth factor receptor 2 inhibitor, for recurrent or metastatic adenoid cystic carcinoma.","volume":"29","author":"Hanna","year":"2023","journal-title":"Clin Cancer Res"},{"issue":"7","key":"ooi250099r9","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1001\/jamaoto.2024.1177","article-title":"Vascular endothelial growth factor receptor inhibitors for recurrent or metastatic adenoid cystic carcinoma: a systematic review and meta-analysis.","volume":"150","author":"Hoff","year":"2024","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"3","key":"ooi250099r10","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1158\/1078-0432.CCR-20-1192","article-title":"Proteogenomic analysis of salivary adenoid cystic carcinomas defines molecular subtypes and identifies therapeutic targets.","volume":"27","author":"Ferrarotto","year":"2021","journal-title":"Clin Cancer Res"},{"issue":"10","key":"ooi250099r11","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1158\/1078-0432.CCR-23-3182","article-title":"Molecular profiling and the impact of treatment on outcomes in adenoid cystic carcinoma type I and II.","volume":"30","author":"Hanna","year":"2024","journal-title":"Clin Cancer Res"},{"key":"ooi250099r12","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1471-2121-14-13","article-title":"EGFR inhibition prevents in vitro tumor growth of salivary adenoid cystic carcinoma.","volume":"14","author":"Huang","year":"2013","journal-title":"BMC Cell Biol"},{"issue":"7","key":"ooi250099r13","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.oraloncology.2008.07.010","article-title":"Cetuximab in recurrent and\/or metastatic salivary gland carcinomas: a phase II study.","volume":"45","author":"Locati","year":"2009","journal-title":"Oral Oncol"},{"issue":"6","key":"ooi250099r14","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1080\/15384047.2015.1030554","article-title":"Analysis and significance of c-MET expression in adenoid cystic carcinoma of the salivary gland.","volume":"16","author":"Bell","year":"2015","journal-title":"Cancer Biol Ther"},{"issue":"6","key":"ooi250099r15","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100319","article-title":"Beyond epidermal growth factor receptor: MET amplification as a general resistance driver to targeted therapy in oncogene-driven non\u2013small-cell lung cancer.","volume":"6","author":"Coleman","year":"2021","journal-title":"ESMO Open"},{"issue":"30","key":"ooi250099r16","doi-asserted-by":"publisher","first-page":"3391","DOI":"10.1200\/JCO.21.00662","article-title":"Amivantamab in EGFR exon 20 insertion-mutated non\u2013small-cell lung cancer progressing on platinum chemotherapy: initial results from the CHRYSALIS phase I study.","volume":"39","author":"Park","year":"2021","journal-title":"J Clin Oncol"},{"issue":"2","key":"ooi250099r17","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"issue":"7","key":"ooi250099r18","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1080\/03610918.2011.560732","article-title":"Confidence intervals for survival probabilities: a comparison study.","volume":"40","author":"Yuan","year":"2011","journal-title":"Commun Stat Simul Comput"},{"issue":"11","key":"ooi250099r19","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1016\/j.oraloncology.2009.05.635","article-title":"Treatment relevant target immunophenotyping of 139 salivary gland carcinomas (SGCs).","volume":"45","author":"Locati","year":"2009","journal-title":"Oral Oncol"},{"issue":"7","key":"ooi250099r20","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1002\/hed.10104","article-title":"Immunohistochemical study of epidermal growth factor receptor in adenoid cystic carcinoma of salivary gland origin.","volume":"24","author":"Vered","year":"2002","journal-title":"Head Neck"},{"issue":"25","key":"ooi250099r21","doi-asserted-by":"publisher","first-page":"3978","DOI":"10.1200\/JCO.2007.11.8612","article-title":"Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and\/or erbB2 expressing adenoid cystic carcinoma and non adenoid cystic carcinoma malignant tumors of the salivary glands.","volume":"25","author":"Agulnik","year":"2007","journal-title":"J Clin Oncol"},{"issue":"5","key":"ooi250099r22","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1002\/hed.23647","article-title":"Phase II study of gefitinib in patients with advanced salivary gland cancers.","volume":"37","author":"Jakob","year":"2015","journal-title":"Head Neck"},{"issue":"5827","key":"ooi250099r23","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1126\/science.1141478","article-title":"MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling.","volume":"316","author":"Engelman","year":"2007","journal-title":"Science"},{"key":"ooi250099r24","doi-asserted-by":"publisher","first-page":"360","DOI":"10.3389\/fonc.2014.00360","article-title":"Notch-EGFR\/HER2 bidirectional crosstalk in breast cancer.","volume":"4","author":"Baker","year":"2014","journal-title":"Front Oncol"},{"issue":"5","key":"ooi250099r25","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1093\/carcin\/bgn079","article-title":"Notch-1 regulates transcription of the epidermal growth factor receptor through p53.","volume":"29","author":"Purow","year":"2008","journal-title":"Carcinogenesis"},{"key":"ooi250099r26","doi-asserted-by":"publisher","first-page":"6655","DOI":"10.2147\/CMAR.S253500","article-title":"Targeting EGFR enriches stem cell-like properties in salivary adenoid cystic carcinoma by activating the Notch1 pathway.","volume":"12","author":"Wang","year":"2020","journal-title":"Cancer Manag Res"},{"issue":"7","key":"ooi250099r27","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1158\/2767-9764.CRC-24-0107","article-title":"Exploration of immune-modulatory effects of amivantamab in combination with pembrolizumab in lung and head and neck squamous cell carcinoma.","volume":"4","author":"Lim","year":"2024","journal-title":"Cancer Res Commun"},{"issue":"5","key":"ooi250099r28","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1097\/IOP.0000000000001585","article-title":"PD-L1 and PD-L2 expression levels are low in primary and secondary adenoid cystic carcinomas of the orbit: therapeutic implications.","volume":"36","author":"Wolkow","year":"2020","journal-title":"Ophthalmic Plast Reconstr Surg"},{"issue":"15","key":"ooi250099r29","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.1200\/JCO.22.02221","article-title":"Phase II clinical trial of axitinib and avelumab in patients with recurrent\/metastatic adenoid cystic carcinoma.","volume":"41","author":"Ferrarotto","year":"2023","journal-title":"J Clin Oncol"}],"container-title":["JAMA Otolaryngology\u2013Head &amp; Neck Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaotolaryngology\/articlepdf\/2845475\/jamaotolaryngology_hanna_2026_oi_250099_1775660465.10435.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T15:00:40Z","timestamp":1775746840000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaotolaryngology\/fullarticle\/2845475"}},"subtitle":["A Phase 2 Nonrandomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoto.2025.5404","relation":{},"ISSN":["2168-6181"],"issn-type":[{"value":"2168-6181","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4,1]]}}}