Datopotamab deruxtecan (Dato-DXd) in locally advanced/metastatic urothelial cancer: Updated results from the phase 1 TROPIONPanTumor01 study.
Funda Meric‐Bernstam, Omar Alhalabi, Aaron Lisberg, Alexandra Drakaki, Benjamin Garmezy, Takahiro Kogawa, Alexander I. Spira, Mohamad A. Salkeni, Xīn Gào, Anthony W. Tolcher, Manali Bhave, Deborah B. Doroshow, Jeannie Hoffman-Censits, G. Klauss, Yoshiaki Kaga, Yasuyuki Kakurai, Takahiro Kojima
Abstract
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 >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.