Sacituzumab Govitecan Plus Pembrolizumab Improves Responses in Bladder Cancer


All prespecified patient subgroups with metastatic urothelial cancer showed a clinical benefit with sacituzumab govitecan plus pembrolizumab in cohort 3 of the phase 2 TROPHY-U-01 trial.

Sacituzumab Govitecan Plus Pembrolizumab Improves Responses in Bladder Cancer

Sacituzumab Govitecan Plus Pembrolizumab Improves Responses in Bladder Cancer

Sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) conferred positive responses with a manageable safety profile in patients with metastatic urothelial cancer with disease progression after prior platinum-containing chemotherapy, as demonstrated in results from cohort 3 of the phase 2 TROPHY-U-01 trial (NCT03547973).

The objective response rate (ORR) based on central review with the experimental combination was 41% (n = 17/41; 95% CI, 26.3-57.9), which reached the trial’s primary end point. Additionally, treatment yielded a complete response (CR) rate of 20% and a partial response (PR) rate of 22%. Stable disease and progressive disease were highlighted in 22% and 24% of patients, respectively. The clinical benefit rate (CBR) was 46% (95% CI, 30.7%-62.6%).

The median duration of response (DOR) among all patients in cohort 3 was 11.1 months (95% CI, 4.8-not estimable [NE]), and the median time to response onset was 1.4 months (95% CI, 1.2-1.5). Additionally, 72% of patients had reductions in target lesions with 1 or more postbaseline target lesion measurements based on central review.

Treatment with sacituzumab govitecan and pembrolizumab produced a median progression-free survival (PFS) of 5.3 months (95% CI, 3.4-10.2) and a median overall survival (OS) of 12.7 months (95% CI, 10.7-NE). There were 20 patients who died as of July 26, 2022; 19 died due to progressive disease.

“In this study, [sacituzumab govitecan] in combination with pembrolizumab showed encouraging antitumor efficacy with a 41% ORR and a CR [rate] of 20% in a platinum-relapsed/refractory patient population, meeting the primary end point,” the study authors wrote. “Clinical benefit was observed across all prespecified subgroups, including patients with liver metastases and 1 or more Bellmunt risk factors, although patient numbers were small in many subgroups, warranting further evaluation in larger trials.”

In cohort 3 of the TROPHY-U-01 trial, 41 patients received sacituzumab govitecan intravenously at 10 mg/kg on days 1 and 8 plus 200 mg of pembrolizumab intravenously on day 1 of a 21-day cycle. Study treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent.

The trial’s primary end point was ORR based on central review using RECIST v1.1 criteria. Secondary end points included DOR, CBR, PFS, OS, and safety and tolerability.

Patients 18 years and older with histologically confirmed locally advanced or metastatic urothelial cancer whose disease progressed following platinum-based chemotherapy in the advanced or metastatic setting were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1 and no active autoimmune disease that needed to be managed within 2 years of study entry.

The median patient age was 67 years (range, 46-86), and 63% of the cohort was 65 years and older. Most patients were male (83%), White (54%), had an ECOG performance status of 1 (61%), metastatic disease (78%), and visceral metastases in the lung/pleura (54%). Additionally, most received prior chemotherapy with cisplatin (71%) and had their most recent prior line of therapy in the metastatic setting (59%).

Any-grade treatment-related adverse effects (TRAEs) occurred in all 41 patients who received treatment in cohort 3, the most common of which included diarrhea (71%), nausea (56%), neutropenia (51%), anemia (49%), asthenia (41%), alopecia (39%), fatigue (32%), and vomiting (29%). Additionally, 46%, 39%, and 15% of patients required sacituzumab govitecan interruptions, dose reductions, and treatment discontinuation, respectively, due to TRAEs.

Investigators highlighted grade 3 or higher TRAEs in 61% of patients; the most common toxicities of this type included neutropenia (37%), diarrhea (20%), leukopenia (20%), anemia (17%), and febrile neutropenia (10%). Serious grade 3 or higher TRAEs included pneumonitis in 2 patients, febrile neutropenia in 3, and diarrhea in 4. There were no deaths related to study treatment.


Grivas P, Pouessel D, Park CH, et al. Sacituzumab govitecan in combination with pembrolizumab for patients with metastatic urothelial cancer that progressed after platinum-based chemotherapy: TROPHY-U-01 cohort 3. J Clin Oncol. Published online January 23, 2024. doi:10.1200/JCO.22.02835

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