Reference Detail

Ref Type

Journal Article

PMID

(32694157)

Authors

Tolaney SM, Do KT, Eder JP, LoRusso PM, Weekes CD, Chandarlapaty S, Chang CW, Chen SC, Nazzal D, Schuth E, Brunstein F, Carrasco-Triguero M, Darbonne WC, Giltnane JM, Flanagan WM, Commerford SR, Ungewickell A, Shapiro GI, Modi S

Title

A Phase I Study of DLYE5953A, an Anti-LY6E Antibody Covalently Linked to Monomethyl Auristatin E, in Patients with Refractory Solid Tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	26	21	2020 Nov 01	5588-5597	Clin Cancer Res

URL

Abstract Text

DLYE5953A is an antibody-drug conjugate consisting of an anti-LY6E antibody covalently linked to the cytotoxic agent monomethyl auristatin E. This study characterized the safety, pharmacokinetics, immunogenicity, potential biomarkers, and antitumor activity of DLYE5953A in patients with metastatic solid tumors.This was a phase I, open-label, 3+3 dose-escalation, and dose-expansion study of DLYE5953A administered intravenously every 21 days (Q3W) in patients with locally advanced or metastatic solid malignancies.Sixty-eight patients received DLYE5953A (median, four cycles; range, 1-27). No dose-limiting toxicities were identified during dose escalation (0.2-2.4 mg/kg; n = 20). The recommended phase II dose (RP2D) of 2.4 mg/kg Q3W was based on overall safety and tolerability. Dose-expansion cohorts for HER2-negative metastatic breast cancer (HER2-negative MBC; n = 23) and non-small cell lung cancer (NSCLC; n = 25) patients were enrolled at the RP2D. Among patients receiving DLYE5953A 2.4 mg/kg (n = 55), the most common (≥30%) related adverse events (AEs) included alopecia, fatigue, nausea, and peripheral neuropathy. Grade ≥3 related AEs occurred in 14 of 55 (26%) patients, with neutropenia being the most common (13%). DLYE5953A demonstrated linear total antibody pharmacokinetics at doses of ≥0.8 mg/kg with low unconjugated monomethyl auristatin E levels in blood. Partial response was confirmed in eight of 68 (12%) patients, including three of 29 patients with MBC (10%) and five of 25 patients with NSCLC (20%) at the RP2D. Stable disease was the best response for 37 of 68 (54%) patients.DLYE5953A administered at 2.4 mg/kg has acceptable safety. Preliminary evidence of antitumor activity in patients with HER2-negative MBC and NSCLC supports further investigation of LY6E as a therapeutic target.

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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
DLYE5953A	DLYE5953A	0	0

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
DLYE5953A		RG 7841\|RG-7841\|RG7841		DLYE5953A is an antibody drug conjugate comprising of an anti-Ly6E monoclonal antibody linked to monomethyl auristatin E, with potential to inhibit tumor growth and proliferation (PMID: 32694157).

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