690P Ifinatamab deruxtecan (I-DXd; DS-7300) in patients with advanced solid tumors: Updated clinical and biomarker results from a phase I/II study

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. 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. 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.Table: 690PEfficacyCRPCESCCsqNSCLCSCLCNo. of prior lines, median (range)6 (1 – 11)4 (1 – 7)3 (1 – 12)2 (1 – 9)ORR by RECIST v1.1 (confirmed) n (%)n = 59 15 (25)n = 28 6 (21)n = 13 4 (31)n = 21 11 (52)DOR by RECIST v1.1 Median, mo (95% CI)n = 59 6.4 (2.8 – 10.6)n = 28 3.5 (2.4 – NE)n = 13 4.1 (2.8 – NE)n = 21 5.9 (2.8 – 7.5)PFS by RECIST v1.1 Median, mo (95% CI)n = 73 4.8 (3.9 – 5.9)n = 28 2.8 (1.6 – 4.2)NRn = 21 5.8 (3.9 – 8.1)OS Median, mo (95% CI)n = 73 13.5 (10.3 – 16.6)n = 28 7.0 (4.8 – 12.2)NRn = 21 9.9 (5.8 – NE)DOR, duration of response; NE, not estimable; NR, not reported; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; RECIST, Response Evaluation Criteria In Solid Tumors. Open table in a new tab DOR, duration of response; NE, not estimable; NR, not reported; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; RECIST, Response Evaluation Criteria In Solid Tumors. 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.