453O DS-7300 (B7-H3 DXd antibody-drug conjugate [ADC]) shows durable antitumor activity in advanced solid tumors: Extended follow-up of a phase I/II study

B7-H3 overexpression correlates with poor prognosis in many cancers. DS-7300 is a B7-H3–directed ADC with a topoisomerase I inhibitor payload (DXd). The DS-7300 dose finding study (NCT04145622) showed that DS-7300 was generally well tolerated with early signs of antitumor activity. We present extended follow-up data for a larger cohort of participants (pt) with selected tumor types. This Ph 1/2 first-in-human study of DS-7300 enrolled pts with tumors unselected for B7-H3 expression; 12.0 mg/kg was selected for the ongoing expansion Ph. Efficacy/safety analyses included pts in the 4.8- to 16.0-mg/kg cohorts; efficacy was evaluated in pts with ≥2 postbaseline scans or discontinuation for any reason. As of Jan 21, 2022, 127 pts (median age of 67 years; n=110 male) received DS-7300 (72 in dose escalation; 55 in dose expansion). Pts had a median 5 prior lines of therapy (range, 1-14). Treatment duration range was 0.1-54 weeks with 51 pts (40%) on treatment. Responses were observed in 30/91 evaluable pts (33%) in total (eg, 7/9 pts with SCLC, 2/5 with sqNSCLC, and 16/42 with mCRPC; Table). Among 6 pts with SCLC and a confirmed PR, median duration of response was 4.4 months (95% CI, 2.8-not reached). The overall safety profile is consistent with previously reported results; treatment-emergent adverse events (TEAEs) occurred in 124 pts (98%); the most common (>30%) were nausea (61%), infusion-related reaction (35%), and vomiting (31%). However, higher rates of serious and grade ≥3 TEAEs within a shorter median treatment duration were noted in the 16.0-mg/kg cohort than the 8.0- and 12.0-mg/kg cohorts.Table: 453OResponses by RECIST v1.1SCLC (n=9)sqNSCLC (n=5)mCRPC (n=42)Study total (N=91a)Responses, n721630bConfirmed PR, n621224Disease control rate (PR+SD), %77.880.073.871.4aAll tumor types; evaluable patients had ≥2 postbaseline scans or discontinuation for any reason; responses in endometrial cancer, esophageal squamous cell carcinoma, head and neck squamous cell carcinoma, mCRPC, SCLC, sqNSCLC. bIncludes 6 unconfirmed PRs; 3 still on treatment. mCRPC, metastatic castration-resistant prostate cancer; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumours; SCLC, small cell lung cancer; SD, stable disease; sqNSCLC, squamous non–small cell lung cancer. Open table in a new tab aAll tumor types; evaluable patients had ≥2 postbaseline scans or discontinuation for any reason; responses in endometrial cancer, esophageal squamous cell carcinoma, head and neck squamous cell carcinoma, mCRPC, SCLC, sqNSCLC. bIncludes 6 unconfirmed PRs; 3 still on treatment. mCRPC, metastatic castration-resistant prostate cancer; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumours; SCLC, small cell lung cancer; SD, stable disease; sqNSCLC, squamous non–small cell lung cancer. DS-7300 continues to demonstrate evidence of durable antitumor activity in heavily pretreated pts with SCLC, sqNSCLC, and mCRPC. These data support further clinical development of DS-7300, including a Ph 2 dose-optimization study in SCLC (NCT05280470) with starting dose levels of 8 mg/kg and 12.0 mg/kg.