Skip to main content

20-02-2022 | ASCO GU 2022 | Conference coverage | News

​​​​​​​Sacituzumab govitecan–pembrolizumab combo encouraging for pretreated mUC

Author: Shreeya Nanda


medwireNews: Combination treatment with sacituzumab govitecan (SG) plus pembrolizumab has encouraging efficacy in metastatic urothelial cancer (mUC) patients who have progressed on platinum-based therapy, report the TROPHY-U-01 researchers.

Speaking at the 2022 ASCO Genitourinary Cancers Symposium in San Francisco, California, USA, investigator Petros Grivas (University of Washington, Seattle, USA) said that “these data support further evaluation of SG plus checkpoint inhibition in metastatic urothelial cancer in the platinum-refractory setting and probably in earlier lines of therapy with a different patient population.”

Petros Grivas explains why sacituzumab govitecan plus pembrolizumab – investigated in cohort 3 of the TROPHY-U-01 study comprising metastatic urothelial cancer patients with progression after platinum-based treatment – is not ready for prime time, but merits further investigation in this setting (5:08).

He presented data on 41 patients aged a median of 67 years included in cohort 3 of the phase 2 trial, all of whom had previously received platinum-based chemotherapy (no more than two prior regimens) but were naïve to immune checkpoint inhibitor therapy (ICI).

About half (49%) had received systemic therapy in the neoadjuvant or adjuvant setting, while the rest (51%) had received it in the first-line metastatic setting. Grivas pointed out that the median time from the last chemotherapy dose in the metastatic setting to screening for this trial was 1.6 months, which means “this is a population of patients with rapid progression.”

Participants were followed up for a median of 5.8 months, during which treatment with the Trop-2-directed antibody–drug conjugate (ADC) SG at a dose of 10 mg/kg on days 1 and 8 of each 21-day cycle together with pembrolizumab 200 mg on day 1 achieved an objective response rate of 34%. One patient had a complete response and the remaining 13 had partial responses.

A further 27% of patients had stable disease, which gave a clinical benefit rate of 61%. The median duration of response had not been reached at the time of analysis and neither had median OS; the median progression-free survival was 5.5 months.

The presenter said that “SG plus pembrolizumab had a manageable safety profile, with no new safety signals.”

Treatment-related adverse events (TRAEs) of grade 3–4 occurred in 59% of patients and 39% required a dose reduction of SG due to a TRAE. There were no treatment-related deaths in the cohort.

A quarter of the patients required steroids for immune-related AEs, with 15% needing topical steroids and 10% oral, while 29% needed granulocyte colony stimulating factor.

Grivas concluded that “additional follow-up for survival events and biomarkers is ongoing,” as is the assessment of other cohorts of the TROPHY-U-01 trial.

Discussant Guru Sonpavde, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, said that the data for combined ADC–ICI treatment are promising but asked whether there could be better patient and drug selection.

He outlined several unanswered research questions, such as whether Trop2 gene expression could be used to select patients, would an ADC that is less myelosuppressive than SG perhaps fare better in combination with pembrolizumab, and would combining ADCs with platinum or a PARP inhibitor rather than with an ICI improve outcomes.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany

ASCO Genitourinary Cancers Symposium; San Francisco, California, USA: 17–19 February 2022