Izalontamab (SI-B001), a novel EGFR\/HER3 bispecific monoclonal antibody, was well-tolerated and exhibited preliminary antitumor activity in previously treated patients with locally advanced or metastatic epithelial tumors, according to results of a phase 1\/1b study (NCT04603287).1<\/p>\n
With a median follow-up of 27.5 months, the most common treatment-related adverse events among 60 enrolled patients were rash (42%), paronychia (25%), and infusion-related reactions. Rashes were reported to be mild, generally grade 1 or grade 2 events. In terms of pharmacokinetics, the agent demonstrated nonlinearity, and no dose-limiting toxicities were observed.<\/p>\n
\u201cThis phase [1] study demonstrates that izalontamab, a novel EGFR\/HER3 bispecific antibody, can be safely administered with an acceptable toxicity profile in patients with advanced epithelial tumors,\u201d said authors Xue et al in Clinical Cancer Research.1<\/p>\n
Early efficacy signals were also observed among the 57 efficacy-evaluable patients, with a confirmed objective response rate of 4%. This included 2 confirmed partial responses in 2 patients with non\u2013small cell lung cancer (NSCLC) and head and neck cancer squamous cell carcinoma. Eighteen patients, including 17 patients with NSCLC and 1 patient with colorectal cancer, had stable disease.<\/p>\n
These encouraging results support the advancement of izalontamab for further clinical evaluation at the established recommended phase 2 dose of 9 to 19 mg\/kg weekly.<\/p>\n
Izalontamab is also the backbone of the bispecific antibody-drug conjugate (ADC) izalontamab brengitecan (iza-bren; BL-B01D1), which earned FDA breakthrough designation<\/strong><\/a> in EGFR-positive NSCLC earlier this year. A recent presentation at the 2025 European Society for Medical Oncology (ESMO) Congress<\/strong><\/a> reported superior overall response rate with iza-bren compared with chemotherapy in nasopharyngeal cancer (54.6% vs 27%) in an ongoing phase 3 trial (NCT06118333).<\/p>\n \u201cThese findings also provide insights into further development of the ADC [iza-bren], which shares the same antibody but adds a cytotoxic payload,\u201d added the authors.1<\/p>\n Study Design and Patient Characteristics<\/p>\n The multicenter, open-label, single-arm phase 1 study aimed to characterize the safety, tolerability, and pharmacokinetics of izalontamab, consisting of dose-escalation and dose-expansion stages.2 A total of 60 adult patients with advanced unresectable or metastatic solid tumors who had failed standard treatment were enrolled. Over 3 tumor types were represented in the population: NSCLC (n = 49), nasopharyngeal cancer (n = 6), head and neck cancer squamous cell carcinoma (n = 3), among other types (n = 2). Eighteen patients had EGFR mutations.<\/p>\n The dose-escalation stage involved accelerated titration followed by a 3+3 design. Next, the dose-expansion stage evaluated 5 dose levels of izalontamab: 6.0, 9.0, 12.0, 16.0, and 21.0 mg\/kg. All patients received intravenous izalontamab weekly or every 2 weeks for 28 mg\/kg in a 4-week cycle.<\/p>\n Biomarker analyses were also performed to examine EGFR and HER3 expression in available pretreatment tumor tissues by immunohistochemistry assay.<\/p>\n Other Studies of Izalontamab<\/p>\n A randomized phase 3 trial (NCT06382129) is underway and recruiting patients. This study is evaluating the efficacy and safety of izalontamab in combination with docetaxel in advanced or metastatic EGFR wild-type NSCLC following treatment failure with anti\u2013PD-1\/PD-L1 monoclonal antibodies and platinum-based chemotherapy.3 The trial aims to enroll 680 patients and is slated to complete in mid-2026.<\/p>\n REFERENCES1. Xue J, Ma Y, Zhao Y, et al. Izalontamab (SI-B001), a novel EGFRxHER3 bispecific antibody in patients with locally advanced or metastatic epithelial tumor: results from first-in-human phase I\/Ib study.\u00a0Clin Cancer Res. 2025;31(21):4438-4445. doi:10.1158\/1078-0432.ccr-25-02062. A study of SI-B001, an EGFR\/HER3 bispecific antibody, in locally advanced or metastatic epithelial tumors. ClinicalTrials.gov. Updated September 26, 2025. Accessed November 5, 2025. https:\/\/clinicaltrials.gov\/study\/NCT04603287<\/a>3. A study comparing BL-B01D1 with docetaxel in patients with unresectable locally advanced or metastatic EGFR wild-type non-small cell lung cancer. ClinicalTrials.gov. Updated May 2, 2025. Accessed November 5, 2025. https:\/\/www.clinicaltrials.gov\/study\/NCT06382129<\/a> <\/p>\n","protected":false},"excerpt":{"rendered":"Izalontamab (SI-B001), a novel EGFR\/HER3 bispecific monoclonal antibody, was well-tolerated and exhibited preliminary antitumor activity in previously treated…\n","protected":false},"author":2,"featured_media":168685,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[78],"tags":[18,135,19,17],"class_list":{"0":"post-168684","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-eire","9":"tag-health","10":"tag-ie","11":"tag-ireland"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ie\/115510774649197178","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/168684","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=168684"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/168684\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/168685"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=168684"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=168684"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=168684"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}