Advertisement


Xin Gao, MD, on Advanced or Metastatic Urothelial Carcinoma: LY4101174

ASCO 2026

Advertisement

Xin Gao, MD, of Massachusetts General Hospital and Harvard Medical School, discusses initial results from the phase I EXCEED trial of LY4101174, a Nectin-4–targeting antibody-drug conjugate, for patients with advanced or metastatic urothelial carcinoma (Abstract 4517).



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
This is a clinical trial that was performed as a dose-escalation study in patients with advanced metastatic urothelial carcinoma as well as other solid tumors known to express Nectin-4. The background for this study is that we know that enfortumab vedotin and pembrolizumab have really revolutionized the treatment for patients with advanced and metastatic urothelial cancers. But unfortunately, treatment resistance and treatment intolerability become an issue. Patients do need additional treatments beyond EV plus pembrolizumab, and unfortunately, at this time, the standard of care remains unclear and prognosis remains poor for patients who need another therapy beyond EV and pembrolizumab. We conducted this phase 1 clinical trial with a dose-escalation design. Eighty-six patients in total had metastatic urothelial cancers, and we looked at various dose levels, starting with low doses, Q2-week dosing as well as Q3-week dosing, which was explored after patients developed DLTs at the third dose level of Q2-week dosing. The vast majority of patients were heavily pretreated patients. Median lines of prior therapy was 3; 88% of patients had received prior platinum-based chemotherapy, 92% had received prior enfortumab vedotin, and all patients had received prior immune checkpoint inhibitors. So I think this was a study that really captured, you know, what's going on in the real world when patients need to think about another therapy beyond EV plus pembrolizumab and platinum-based chemotherapy. What we saw was that there was antitumor activity, particularly at the highest dose level of 4 mg/kg Q3-week dosing. We saw an objective response rate of 36% with the dose, with a disease control rate of 76%. However, we also ran into dose-limiting and significant hematologic toxicities, including grade 3 or higher anemia, neutropenia, thrombocytopenia, as well as febrile neutropenia at the highest dose level despite use of G-CSF prophylaxis. So the EXCEED study was a proof of concept that further targeting of Nectin-4 remains a viable and important clinical strategy for patients with treatment-refractory metastatic urothelial cancers after enfortumab vedotin. I think future work will be needed to continue to develop and study newer, other kinds of Nectin-4-targeting drugs with different payloads, different linkers, that hopefully will be able to find a dose that's both efficacious and tolerable for patients.

Related Videos

Lung Cancer

Christine Lovly, MD, PhD, FASCO, on Adjuvant Selpercatinib in RET Fusion–Positive Early-Stage NSCLC: Expert Perspective

Christine Lovly, MD, PhD, FASCO, of City of Hope, offers her thoughs on the findings of the LIBRETTO-432 trial, which found improved event-free survival with adjuvant selpercatinib after definitive therapy for patients with early-stage RET fusion–positive non–small cell lung cancer (NSCLC) (Abstract LBA3).  

Gastroesophageal Cancer

Elena Elimova, MD, on PD-L1 Subgroup Analysis From HERIZON-GEA-01

Elena Elimova, MD, Princess Margaret Cancer Centre, discusses the efficacy in PD-L1 subgroups of zanidatamab plus chemotherapy with or without tislelizumab as a first-line regimen for HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma (Abstract 4010).

Lung Cancer

Giannis S. Mountzios, MD, on SCLC: Intracranial Effect of Tarlatamab vs Chemotherapy

Giannis S. Mountzios, MD, of Henry Dunant Hospital Center, discusses findings from a post hoc analysis of the phase III DeLLphi-304 trial, which examined the intracranial efficacy of tarlatamab vs chemotherapy as second-line therapy for small cell lung cancer (SCLC) (Abstract 8006).

Breast Cancer

Yashasvini Sampathkumar, MD, on Job Retention Intervention for Patients Undergoing Breast Cancer Therapy: Digital vs Print Format

Yashasvini Sampathkumar, MD, of Memorial Sloan Kettering Cancer Center, presents data on Talking to Employers and Medical Staff about Work (TEAMWork), an English/Spanish intervention. The English/Spanish intervention, delivered as a booklet or mobile app, was developed to improve work outcomes among women undergoing breast cancer therapy. Dr. Sampathkumar discusses whether the digital vs print format was preferable among this population (Abstract 11060). 

Lung Cancer

John V. Heymach, MD, PhD, on First-Line Therapy for Advanced NSCLC With EGFR Exon 20 Insertions

John V. Heymach, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses results from the primary analysis of the multinational phase III WU-KONG28 trial, which looked at sunvozertinib monotherapy vs platinum-based therapy as first-line treatment for patients with advanced non–small cell lung cancer (NSCLC) and EGFR exon 20 insertions (Abstract LBA8500). 

Advertisement

Advertisement




Advertisement