Datopotamab deruxtecan (Dato-DXd) in locally advanced/metastatic urothelial cancer: Updated results from the phase 1 TROPIONPanTumor01 study.
Authors: Funda Meric-Bernstam, Omar Alhalabi, Aaron Lisberg, Alexandra Drakaki, Benjamin Garmezy, Takahiro Kogawa, Alexander I. Spira, Mohamad Adham Salkeni, Xin Gao, Anthony W. Tolcher, Manali A. Bhave, Deborah Blythe Doroshow, Jeannie Hoffman-Censits, Gunnar Klauss, Yoshiaki Kaga, Yasuyuki Kakurai, Takahiro Kojima
Journal: Journal of Clinical Oncology (2025)

663 Background: Dato-DXd is a TROP2-directed antibody-drug conjugate under investigation in various solid tumor types. We report updated results in patients (pts) with locally advanced/metastatic urothelial cancer (la/m UC) from the ongoing phase 1 TROPION-PanTumor01 study (NCT03401385). Methods: Pts with unresectable la/m UC (stage III/IV) treated with ≥1 prior line of therapy, including an immune checkpoint inhibitor, received Dato-DXd 6 mg/kg Q3W. Primary study objectives were safety and tolerability. Secondary endpoints were objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) per RECIST 1.1 by blinded independent central review (BICR). Results: At data cutoff (April 22, 2024), 40 pts had received Dato-DXd; 8 (20%) were receiving ongoing treatment. Median follow-up was 10.0 (range 5–28) months (mo). Pts were heavily pretreated: 24 (60%) had received ≥3 prior regimens in the locally advanced/metastatic setting, 36 (90%) received prior platinum chemotherapy, and 33 (83%) received prior enfortumab vedotin. Confirmed ORR by investigator was 27.5% (95% CI, 14.6–43.9), including 11 partial responses (PR). Confirmed ORR by BICR was 25.0% (95% CI, 12.7–41.2), including 1 complete response (CR) and 9 PR (Table). Median DOR was not reached (95% CI, 2.6–not evaluable [NE]); 76.2% (95% CI, 33.2–93.5) of responders had ongoing responses at 6 mo. Median PFS by BICR was 6.9 mo (95% confidence interval [CI], 2.9–NE). Treatment-emergent adverse events (TEAEs) occurring in &gt;20% of pts (any grade; grade ≥3) were stomatitis (53%; 5%), nausea (38%; 3%), decreased appetite (30%; 3%), and fatigue (28%; 0%). Grade ≥3 TEAEs occurred in 55% of pts. TEAEs associated with treatment discontinuation, dose reduction, and dose interruption occurred in 8%, 20%, and 35% of pts, respectively. No serious treatment-related AEs or treatment-related grade 4 or 5 AEs were reported. Two pts (5%) had adjudicated drug-related interstitial lung disease/pneumonitis (grade 2 and 3). Conclusions: In heavily pretreated pts with la/m UC, Dato-DXd demonstrated encouraging antitumor activity with a manageable safety profile. Dato-DXd is being evaluated in pts with urothelial cancer in the phase 1/2 TROPION-PanTumor02 (NCT05460273) and the phase 2 TROPION-PanTumor03 (NCT05489211) studies. Clinical trial information: NCT03401385 . Efficacy by BICR. Response All patients N=40 Confirmed ORR, n (%) [95% CI] 10 (25.0) [12.7–41.2] CR 1 (2.5) PR 9 (22.5) SD 20 (50.0) Non-CR/non-PD 1 (2.5) PD 5 (12.5) NE 4 (10.0) DOR at 6 mo, % [95% CI] 76.2 [33.2–93.5] Median PFS, mo [95% CI] 6.9 [2.9–NE] BICR, blinded independent central review; CI, confidence interval; CR, complete response; DOR, duration of response; mo, months; NE, not evaluable; ORR, objective response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.