^
    almost2years
    Phase II Trial of CDX-3379 and Cetuximab in Recurrent/Metastatic, HPV-Negative, Cetuximab-Resistant Head and Neck Cancer. (PubMed, Cancers (Basel))
    Dual ErbB3-EGFR inhibition remains of scientific interest in HPV-negative HNSCC. Should more tolerable combinations be identified, development in an earlier line of therapy and prospective evaluation of the FAT1 hypothesis warrant consideration.
    P2 data • Journal
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    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • FAT1 (FAT atypical cadherin 1)
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    FAT1 mutation
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    Erbitux (cetuximab) • CDX-3379
    over2years
    Enhancing Radioiodine Incorporation in BRAF-Mutant, Radioiodine-Refractory Thyroid Cancers with Vemurafenib and the Anti-ErbB3 Monoclonal Antibody CDX-3379: Results of a Pilot Clinical Trial. (PubMed, Thyroid)
    The endpoints for success were met, providing preliminary evidence of vemurafenib+CDX-3379 safety and efficacy for enhancing RAI uptake. Preclinical data and genomic profiling in this small cohort suggest SWI/SNF gene mutations should be investigated as potential markers of resistance to redifferentiation strategies. Further evaluation of vemurafenib+CDX-3379 as a redifferentiation therapy in a larger trial is warranted. (ClinicalTrials.gov: NCT02456701).
    Clinical • Journal
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    BRAF (B-raf proto-oncogene) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • TERT (Telomerase Reverse Transcriptase) • ARID2 (AT-Rich Interaction Domain 2) • TG (Thyroglobulin)
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    BRAF V600E • BRAF mutation • BRAF V600
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    Zelboraf (vemurafenib) • CDX-3379
    almost4years
    [VIRTUAL] Novel multimodal precision immunotherapy by co-targeting the HER3 oncogenic signaling circuitry and PD-1 for head and neck squamous cell carcinoma (AACR-II 2020)
    These include immune check point blockade with pembrolizumab and nivolumab (anti-PD-1), which have recently demonstrated anti-tumor activity in HNSCC, albeit only <20% of the patients show durable responses...Furthermore, a blocking antibody targeting HER3 (CDX-3379) potently inhibited the tumor growth of PIK3CA wild type but not PIK3CA mutant HNSCC cells...Overall, our findings suggest that persistent tyrosine phosphorylation of HER3 underlies aberrant PI3K/mTOR signaling in HNSCC harboring wild type PIK3CA, and that targeting HER3 may exert its anti-tumor effect by both reducing cancer-driving mTOR activity and reversing an immune evasive tumor microenvironment. These findings also support that co-targeting the HER3 signaling circuitry combined with PD-1 blockade may represent a novel multimodal precision therapeutic approach for HNSCC aimed at achieving durable responses and cancer remission.
    Late-breaking abstract • PD(L)-1 Biomarker • IO biomarker
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    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IL6 (Interleukin 6) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • CSF2 (Colony stimulating factor 2)
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    PIK3CA mutation • ERBB3 expression • ERBB3 mutation
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    Keytruda (pembrolizumab) • Opdivo (nivolumab) • CDX-3379
    over4years
    Study of CDX-3379, a Human Monoclonal Antibody Targeting ERBB3, in Combination With the MEK Inhibitor, Trametinib, in Patients With Advanced Stage NRAS Mutant and BRAF/NRAS Wildtype (WT) Melanoma (clinicaltrials.gov)
    P1/2, N=3, Terminated, NYU Langone Health | N=10 --> 3 | Recruiting --> Terminated; Per regulatory coordinator, the sponsor is no longer supporting the study.
    Clinical • Enrollment change • Trial termination • Combination therapy
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    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
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    BRAF mutation • NRAS mutation • NRAS Q61
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    Mekinist (trametinib) • CDX-3379
    over6years
    A Phase 1 Study to Evaluate the Safety and Pharmacokinetics of KTN3379 in Adult Subjects With Advanced Tumors (clinicaltrials.gov)
    P1, N=24, Recruiting, Kolltan Pharmaceuticals, Inc.
    Clinical • New P1 trial • P1 data
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
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    HER-2 positive • BRAF V600E • BRAF V600 • EGFR expression
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    CDX-3379