David Aggen, Assistant Attending at Memorial Sloan Kettering Cancer Center, shared a post on LinkedIn:
“Excited for ASCO presentation from Gopa Iyer from Memorial Sloan Kettering Cancer Center with data showing activity of a next generation ADC targeting nectin-4.
As enfortumab vedotin plus pembrolizumab (EV/P) establishes itself as the frontline standard for metastatic urothelial carcinoma and MiBC, a critical question arises: what are the next steps after progression on EV-based therapy?
The phase 1 NEXUS-01 study evaluating LY4052031 presents an intriguing early signal in this context. LY4052031 is a next-generation anti–Nectin-4 antibody-drug conjugate that employs a novel topoisomerase I payload (Camp98), differing from the MMAE payload used with enfortumab vedotin. Emerging preclinical evidence indicating that resistance to EV may often be mediated by the payload rather than a complete loss of Nectin-4 target expression.
Key findings from the initial dose-escalation cohort include:
- An overall response rate (ORR) of 48% with a disease control rate of 81% in efficacy-evaluable metastatic urothelial carcinoma patients treated at active dose levels.
- In patients previously treated with EV (including EV/P), the ORR remained at 40%.
- One complete response was documented.
- The median duration of response was 7 months.
- Safety appeared manageable overall, with CYP2D6-guided dose optimization now integrated into the study design.
While these early-phase data involve small patient numbers, the study underscores an important evolving concept in urothelial cancer therapeutics: sequential targeting of the same antigen with differentiated antibody-drug conjugate platforms and biomarkers informed sequencing.
Abstract: ASCO NEXUS-01 Abstract
See the full presentation on May 29th at ASCO 2026″
Title: Initial results from NEXUS-01, a phase 1 study of LY4052031, an antibody-drug conjugate targeting Nectin-4, in participants with advanced or metastatic urothelial carcinoma.
Author: Gopa Iyer
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