FDA Grants Fast Track Designation to Sacituzumab Govitecan in Locally Advanced mUC

Sacituzumab govitecan has been granted Fast Track designation by the FDA for the treatment of patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting, including patients who are platinum-ineligible and have previously received a PD-1/PD-L1 inhibitor in the neoadjuvant/adjuvant, locally advanced, or metastatic setting, Immunomedics, Inc announced in a press release.¹

“With the upcoming maturation of the data from the 100-patient cohort with prior platinum-based and PD-1 or PD-L1 inhibitor therapies, and based on the Fast Track designation, we will actively seek guidance from the FDA on a potential accelerated approval pathway,” said Loretta M. Itri, MD, chief medical officer at Immunomedics.

Sacituzumab govitecan is currently being studied in cohort 1 of the phase II TROPHY U-01 study, for which interim results were presented at the 2019 European Society of Medical Oncology (ESMO) Annual Meeting. The findings showed significant antitumor activity with sacituzumab govitecan, and the drug was well-tolerated in patients.

The analysis included 35 patients in total. At baseline, these patients had a median age of 64 years (range, 43-90). Of the patients assessed, 77% had received a median of 3 prior therapies (range, 2-7).²

After follow-up of a median of 4.1 months, the objective response rate (ORR) was 29%, which included 2 confirmed complete responses, 5 confirmed partial response (PRs), and 3 unconfirmed PRs. At the time of data cutoff, responses in these patients were ongoing and pending radiographic confirmation. Additionally, target lesion reduction occurred in 74% of patients (n = 23). In a small subgroup of patients with liver involvement, the ORR was 25%.

In terms of safety, this study showed a similar profile to prior reports. Grade 3 or higher adverse events (AEs) were observed in patients, with the most common being neutropenia (23%), anemia (17%), febrile neutropenia (11%), and diarrhea (11%). Interstitial lung disease, ocular toxicities, or grade >2 neuropathy were not reported in the study population. No deaths occurred as a result of treatment with sacituzumab govitecan.

The ongoing global, open-label, TROPHY U-01 is enrolling 201 participants, 100 of which will be a part of cohort 1. Patients will receive 10 mg/kg of sacituzumab govitecan to assess the antitumor activity of the drug. The primary end point of the study is ORR, and the secondary end points include duration of response, progression-free survival, overall survival, and clinical benefit rate.

To be eligible for the study, patients are required to have mUc with measurable disease, and ECOG performance status of 0 or 1, and creatinine clearance ≥30 mL/min. The study follows a Simon 2-stage design and results are based on Investigator assessment.  

This Fast Track designation comes on the heels of anFDA approval of sacituzumab govitecan in metastatic triple-negative breast cancerbased on the results from the phase III ASCENT trial.

Topline data for sacituzumab govitecan in mUC will be announced in the second half of 2020.¹

References

1. FDA grants Fast Track Designation to sacituzumab govitecan for metastatic urothelial cancer [new release]. Morris Plains, New York. Immunomedics, Inc; April 7, 2020.https://bit.ly/2x3NYAq. Accessed April 7, 2020.
2. Tagawa ST, Balar A, Petrylak et al. Initial results from TROPHY-U-01: A phase II open-label study of sacituzumab govitecan in patients (Pts) with metastatic urothelial cancer (mUC) after failure of platinum-based regimens (PLT) or immunotherapy. Ann Oncol. 30:5; 890-v891.