Dr Sonpavde on Early Data With Sacituzumab Govitecan Plus Ipilimumab/Nivolumab in Urothelial Cancer

Guru P. Sonpavde, MD, medical director, Genitourinary (GU) Oncology, assistant director, the Clinical Research Unit, the Christopher K. Glanz Chair, Bladder Cancer Research, AdventHealth Cancer Institute, discusses initial findings from a phase 1/2 trial (NCT04863885) investigating sacituzumab govitecan-hziy (Trodelvy) plus ipilimumab (Yervoy) and nivolumab (Opdivo) in the treatment of metastatic urothelial cancer.

In this investigator-initiated trial, the TROP-2–targeted antibody-drug conjugate sacituzumab govitecan was evaluated in combination with ipilimumab and nivolumab in patients with cisplatin-ineligible metastatic urothelial cancer (n = 25). The phase 1 component demonstrated the feasibility of this combination, and confirmed that the the recommended phase 2 dose (RP2D) as 8 mg/kg of sacituzumab govitecan on days 1 and 8, along with a 3 mg dose of ipilimumab and a 1 mg dose of nivolumab. This regimen was subsequently advanced into the phase 2 component of the trial.

In the phase 2 component, the overall response rate (ORR) among evaluable patients (n = 178) was 83.3%, with a median duration of response lasting 8.04 months at a median follow-up of 21.57 months. However, the trial was terminated early after accruing a total of 25 patients due to 2 unexpected grade 5 myocarditis events linked to the combination of ipilimumab and nivolumab in the phase 2 cohort (n = 16). Sonpavde says that despite these serious adverse effects (AEs), the combination regimen demonstrated activity, maintaining an ORR of 83.3% in the 18 patients available for efficacy assessment.

Ongoing correlative studies aim to identify predictive factors for immune myocarditis in this patient population. Investigators are exploring whether theUGT1A1 polymorphism, which is known to increase toxicity from the sacituzumab govitecan payload, could play a role in these AEs. They are also examining the potential interaction between single nucleotide polymorphisms and UGT1A1variants in contributing to immune-related AEs, particularly those leading to the observed grade 5 myocarditis events. This research is currently in progress.