First in human, a phase I study of ISU104, a novel ErbB3 monoclonal antibody, in patients with advanced solid tumours

Kim, S.-B.; Keam, Bhumsuk; Shin, Seong-Hoon; Chae, Yee Soo; Kim, T.M.; Kim, M.-S.; Kim, J.G.; Park, K.; Ahn, Jin Seok; Park, L.C.; Lee, E.; Juhn, Jae Ryang; Kim, S.; Hong, Seung‐Beom; Ahn, Myung‐Ju

doi:10.1093/annonc/mdz244.016

Cited by 3 publications

(4 citation statements)

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“… 37 In a first-in-human phase I study of ISU104 in patients with advanced solid tumors, mucositis and diarrhea represented the most frequent TRAEs and among the 15 patients enrolled, seven stable disease and one partial response were observed. 38 …”

Section: Her3-targeting With Monoclonal Antibodiesmentioning

confidence: 99%

Targeting HER3 for cancer treatment: a new horizon for an old target

Uliano

Corvaja²,

Curigliano³

et al. 2023

ESMO Open

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Section: Her3-targeting With Monoclonal Antibodiesmentioning

confidence: 99%

Targeting HER3 for cancer treatment: a new horizon for an old target

Uliano

Corvaja²,

Curigliano³

et al. 2023

ESMO Open

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“…A phase II trial of an anti-HER3 monoclonal antibody, CDX-3379, and cetuximab in a population of heavily pretreated patients with head and neck squamous cell carcinoma (HNSCC) demonstrated antitumor activity with an acceptable safety profile [147]. Additionally, a first-in-human phase I study with ISU104 (ErbB3 monoclonal antibody) in patients with advanced solid tumors showed mucositis and diarrhea represented the most frequent treatment-related adverse events (TRAEs) [170].…”

Section: Her3-directed Monoclonal Antibodies In Other Cancersmentioning

confidence: 99%

HER3: Toward the Prognostic Significance, Therapeutic Potential, Current Challenges, and Future Therapeutics in Different Types of Cancer

Majumder

2023

Cells

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Human epidermal growth factor receptor 3 (HER3) is the only family member of the EGRF/HER family of receptor tyrosine kinases that lacks an active kinase domain (KD), which makes it an obligate binding partner with other receptors for its oncogenic role. When HER3 is activated in a ligand-dependent (NRG1/HRG) or independent manner, it can bind to other receptors (the most potent binding partner is HER2) to regulate many biological functions (growth, survival, nutrient sensing, metabolic regulation, etc.) through the PI3K–AKT–mTOR pathway. HER3 has been found to promote tumorigenesis, tumor growth, and drug resistance in different cancer types, especially breast and non-small cell lung cancer. Given its ubiquitous expression across different solid tumors and role in oncogenesis and drug resistance, there has been a long effort to target HER3. As HER3 cannot be targeted through its KD with small-molecule kinase inhibitors via the conventional method, pharmaceutical companies have used various other approaches, including blocking either the ligand-binding domain or extracellular domain for dimerization with other receptors. The development of treatment options with anti-HER3 monoclonal antibodies, bispecific antibodies, and different combination therapies showed limited clinical efficiency for various reasons. Recent reports showed that the extracellular domain of HER3 is not required for its binding with other receptors, which raises doubt about the efforts and applicability of the development of the HER3-antibodies for treatment. Whereas HER3-directed antibody–drug conjugates showed potentiality for treatment, these drugs are still under clinical trial. The currently understood model for dimerization-induced signaling remains incomplete due to the absence of the crystal structure of HER3 signaling complexes, and many lines of evidence suggest that HER family signaling involves more than the interaction of two members. This review article will significantly expand our knowledge of HER3 signaling and shed light on developing a new generation of drugs that have fewer side effects than the current treatment regimen for these patients.

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“…New agents have also progressed into early‐stage clinical trials, including ISU104 (http://ClinicalTrials.gov Identifier: NCT03552406). ISU104 blocks HER3 activation and heterodimerization, and according to preliminary results from an ongoing phase 1/2 study in refractory solid tumors, it exhibited a disease control rate of 60% 64 …”

Section: Pretreated Egfr‐mutant Nsclcmentioning

confidence: 99%

“…ISU104 blocks HER3 activation and heterodimerization, and according to preliminary results from an ongoing phase 1/2 study in refractory solid tumors, it exhibited a disease control rate of 60%. 64 Another agent in development is TAS0728, a smallmolecule inhibitor of HER2 kinase activity 65 ; it is being investigated in a phase 1/2 trial that is examining its safety and activity in patients with advanced HER2-or HER3-positive tumors (ClinicalTrials.gov Identifier: NCT03410927).…”

Section: Other Agents In the Pipelinementioning

confidence: 99%

New era for emerging therapeutic targeting human epidermal growth factor receptor 3 (HER 3) in advanced nonsmall cell lung cancer and metastatic breast cancer

et al. 2022

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Human epidermal growth factor receptor 3 (HER3) is a member of the transmembrane receptor tyrosine kinase family. Upregulation of HER3 pathway has been implicated as a mechanism of resistance in solid tumors, particularly in estrogen receptor positive, HER2 positive breast cancer and epidermal growth factor (EGFR) mutant nonsmall cell lung cancer. Several studies suggest that HER3 overexpression represents a negative prognostic biomarker associated with poor survival. Preclinical and clinical studies of anti‐HER3 investigational therapies suggest that expression of the HER3 ligand, neuregulin, may predict response to treatment. Despite its emergence as a key cancer therapeutic target, HER3 cannot be targeted with traditional tyrosine kinase inhibitors therapy due to its weak kinase activity. Monoclonal and bispecific antibodies targeting HER3 have been developed and tested in early phase trials. Objective responses were limited when first‐generation HER3‐specific monoclonal antibodies were investigated as monotherapies in phase 1 and 2 clinical trials for nonsmall cell lung cancer (NSCLC) and metastatic breast cancer (MBC). MBC and NSCLC HER3 specific antibody‐drug conjugates have shown encouraging results in resistance in cancer cells, particularly in those that overexpress HER3. These agents have shown some promise in early phase trials in both NSCLC and MBC setting in heavily pretreated patients with varying degrees of response. It is unclear which subgroup of patients will truly benefit from targeting HER3 as these therapies are under investigation.

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First in human, a phase I study of ISU104, a novel ErbB3 monoclonal antibody, in patients with advanced solid tumours

Cited by 3 publications

References 0 publications

Targeting HER3 for cancer treatment: a new horizon for an old target

Targeting HER3 for cancer treatment: a new horizon for an old target

HER3: Toward the Prognostic Significance, Therapeutic Potential, Current Challenges, and Future Therapeutics in Different Types of Cancer

New era for emerging therapeutic targeting human epidermal growth factor receptor 3 (HER 3) in advanced nonsmall cell lung cancer and metastatic breast cancer

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