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.

9 months ago

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)

9ms

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.

9 months ago

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)

11ms

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

11 months ago

Trial completion date • Trial primary completion date • Combination therapy • Metastases

EGFR wild-type

Tagrisso (osimertinib) • tilatamig samrotecan (AZD9592)

1year

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.

1 year ago

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)