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    DRUG:

    tilatamig samrotecan (AZD9592)

    i
    Other names: AZD9592, AZD-9592, AZD 9592
    Company:
    AstraZeneca
    Drug class:
    Topoisomerase I inhibitor, EGFR-targeted antibody-drug conjugate, c-MET-targeted antibody-drug conjugate
    Related drugs:
    8ms
    EGRET: First in Human Study of AZD9592 in Solid Tumors (clinicaltrials.gov)
    P1, N=162, Recruiting, AstraZeneca | N=108 --> 162
    Enrollment change • Combination therapy • Metastases
    |
    EGFR wild-type
    |
    Avastin (bevacizumab) • Tagrisso (osimertinib) • 5-fluorouracil • leucovorin calcium • tilatamig samrotecan (AZD9592)
    9ms
    EGRET: First in Human Study of AZD9592 in Solid Tumors (clinicaltrials.gov)
    P1, N=108, Recruiting, AstraZeneca | Trial completion date: Mar 2025 --> Oct 2025 | Trial primary completion date: Mar 2025 --> Oct 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    EGFR wild-type
    |
    Avastin (bevacizumab) • Tagrisso (osimertinib) • 5-fluorouracil • leucovorin calcium • tilatamig samrotecan (AZD9592)
    over1year
    EGRET: First-in-human Study of the Novel Antibody-drug Conjugate AZD9592 ± Anti-cancer Agents in Advanced Solid Tumours (IASLC-WCLC 2023)
    Module 2 will evaluate AZD9592 in combination with osimertinib in patients with EGFRm mNSCLC. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting.
    P1 data • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR expression • EGFR wild-type • MET expression
    |
    Tagrisso (osimertinib) • tilatamig samrotecan (AZD9592)
    over1year
    In Vivo Efficacy of AZD9592, an EGFR-cMET Bispecific ADC, in a Broad Panel of NSCLC Patient-Derived Xenograft Models (IASLC-WCLC 2023)
    Comparable efficacy was observed across EGFR mutant (EGFRm) models previously treated with single or multiple lines of first- (gefitinib, erlotinib), second- (afatinib), and/or third-generation (osimertinib) EGFR TKIs. Additionally, TR was observed in 3/3 (100%) of models previously treated with an EGFR TKI in combination with the cMET TKI savolitinib; high cMET expression by IHC was seen in >90% of the cells in these three models. Notably, 4/5 (80%) of models with prior exposure to the ALK TKI crizotinib demonstrated TR... In vivo efficacy of AZD9592 was demonstrated in PDX models across a broad spectrum of NSCLC molecular profiles. These included EGFRwt and EGFRm tumours harbouring varied EGFR mutations; groups with and without prior chemotherapy; and groups with and without prior treatment with ALK, EGFR, and/or cMET TKI. These observations suggest that AZD9592 may provide clinical benefit in areas of unmet need, including in patients previously treated with chemotherapy or targeted agents.
    Preclinical
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR expression • EGFR wild-type • EGFR L861Q • EGFR S768I • EGFR exon 20 mutation • EGFR G719C
    |
    Xalkori (crizotinib) • Tagrisso (osimertinib) • erlotinib • Gilotrif (afatinib) • gefitinib • Orpathys (savolitinib) • tilatamig samrotecan (AZD9592)
    over1year
    EGRET: First in Human Study of AZD9592 in Solid Tumors (clinicaltrials.gov)
    P1, N=108, Recruiting, AstraZeneca | Trial completion date: Oct 2024 --> Jan 2025 | Trial primary completion date: Oct 2024 --> Jan 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    EGFR wild-type
    |
    Tagrisso (osimertinib) • tilatamig samrotecan (AZD9592)
    over1year
    Evaluation of the relationship between target expression and in vivo anti-tumor efficacy of AZD9592, an EGFR/c-MET targeted bispecific antibody drug conjugate (AACR 2023)
    Collectively, these results support the hypothesized mechanism of action of AZD9592: TOP1i induced tumor cell death due to formation of DNA DSB, and suggest opportunities in the treatment of tumors with a range of molecular features. AZD9592 is currently in a Phase 1 clinical trial in advanced solid malignancies.
    Preclinical
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • SLFN11 (Schlafen Family Member 11) • CASP3 (Caspase 3)
    |
    EGFR mutation • EGFR expression • EGFR wild-type • MET mutation • RAD50 mutation
    |
    tilatamig samrotecan (AZD9592)