Ifinatamab deruxtecan (I-DXd; DS-7300) in patients with advanced solid tumors: Updated clinical and biomarker results from a phase I/II study

Document Type

Conference Proceeding

Publication Date

10-1-2023

Publication Title

Ann Oncol

Abstract

Background: I-DXd is a novel B7-H3–directed antibody–drug conjugate that leverages the clinically validated deruxtecan (DXd) technology with a plasma-stable linker and potent topoisomerase I inhibitor payload. Here we present a follow-up analysis (7 mo since last report) of an ongoing phase 1/2 trial that includes heavily pretreated patients with castration-resistant prostate cancer (CRPC), esophageal squamous cell carcinoma (ESCC), squamous non-small cell lung cancer (sqNSCLC), and small cell lung cancer (SCLC). DOR, OS, and B7-H3 correlations with response are reported for the first time for CRPC, ESCC, and sqNSCLC. Methods: Efficacy and safety were analyzed in patients treated with I-DXd at 4.8 to 16.0 mg/kg. Response was evaluated in patients with ≥2 postbaseline scans or discontinuation for any reason. Fourteen patients with CRPC lacked measurable target lesions at baseline (BL) and were excluded from ORR analysis. B7-H3 level was evaluated retrospectively as patients were not pre-selected by BL expression. Results: As of 31 Jan 2023, 8 patients remained on treatment. Safety data were consistent with previous reports. I-DXd still demonstrated promising ORR results, including in an updated sample size for sqNSCLC (Table). Even in this heavily pretreated population, I-DXd exhibited durable response and encouraging early OS (Table), although further follow-up is needed. B7-H3 expression was moderate to high in most patients; no correlation was observed between response and B7-H3 level, and an update will be presented at the congress. [Formula presented] Conclusions: I-DXd continues to demonstrate a manageable safety profile and promising antitumor activity with encouraging DOR and OS in these heavily pretreated patients, which warrants further clinical evaluation across multiple indications. Clinical trial identification: NCT04145622.

Medical Subject Headings

Hematology

PubMed ID

Not assigned.

Volume

34

First Page

S481

Last Page

S482

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