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Ref Type Journal Article
PMID (30962319)
Authors He K, Xu J, Liang J, Jiang J, Tang M, Ye X, Zhang Z, Zhang L, Fu B, Li Y, Bai C, Zhang L, Tao W
Title Discovery of A Novel EGFR-Targeting Antibody-Drug Conjugate, SHR-A1307, for the Treatment of Solid Tumors Resistant or Refractory to Anti-EGFR Therapies.
Journal Molecular cancer therapeutics
Vol 18
Issue 6
Date 2019 Jun
URL
Abstract Text Although inhibiting EGFR-mediated signaling proved to be effective in treating certain types of cancers, a quickly evolved mechanism that either restores the EGFR signaling or activates an alternative pathway for driving the proliferation and survival of malignant cells limits the efficacy and utility of the approach via suppressing the EGFR functionality. Given the fact that overexpression of EGFR is commonly seen in many cancers, an EGFR-targeting antibody-drug conjugate (ADC) can selectively kill cancer cells independently of blocking EGFR-mediated signaling. Herein, we describe SHR-A1307, a novel anti-EGFR ADC, generated from an anti-EGFR antibody with prolonged half-life, and conjugated with a proprietary toxin payload that has increased index of EGFR targeting-dependent versus EGFR targeting-independent cytotoxicity. SHR-A1307 demonstrated strong and sustained antitumor activities in EGFR-positive tumors harboring different oncogenic mutations on EGFR, KRAS, or PIK3CA. Antitumor efficacy of SHR-A1307 correlated with EGFR expression levels in vitro and in vivo, regardless of the mutation status of EGFR signaling mediators and a resultant resistance to EGFR signaling inhibitors. Cynomolgus monkey toxicology study showed that SHR-A1307 is well tolerated with a wide therapeutic index. SHR-A1307 is a promising therapeutic option for EGFR-expressing cancers, including those resistant or refractory to the EGFR pathway inhibitors.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
SHR-A1307 SHR-A1307 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
SHR-A1307 EGFR Antibody 28 SHR-A1307 is an antibody-drug conjugate that consists of an auristatin analog linked to the anti-EGFR antibody Nimotuzumab with improved half-life, which inhibits cell growth in culture and reduces tumor growth (PMID: 30962319).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PIK3CA H1047R head and neck squamous cell carcinoma resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cells harboring PIK3CA H1047R were resistant to Erbitux (cetuximab) in culture (PMID: 30962319). 30962319
PIK3CA H1047R head and neck squamous cell carcinoma predicted - sensitive SHR-A1307 Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cells harboring PIK3CA H1047R treated with SHR-A1307 demonstrated inhibition of cell growth in culture (PMID: 30962319). 30962319