GU Cancers 2022 | TROPHY-U-01 Cohort 3: sacituzumab govitecan + pembrolizumab for patients with mUC
Petros Grivas, MD, PhD, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, discusses the results of the Phase II TROPHY-U-01 (NCT03547973) trial investigating sacituzumab govitecan (SG) in patients with metastatic urothelial cancer (mUC) who have progressed following platinum-based chemotherapy and checkpoint inhibitors. Platinum-based therapy is the current first-line standard of care (SOC) for patients with advanced UC, however, approximately 50% of patients are ineligible for cisplatin and patients who do receive cisplatin will often progress. Checkpoint blockades are a SOC option for patients who are platinum-ineligible or those who have progressed following platinum therapy. Antibody drug conjugates (ADCs) have demonstrated clinical efficacy in subsequent lines of treatment. SG is an ADC targeted to the surface protein Trop2, an antigen which has shown to be overexpressed in UC. TROPHY-U-01 consisted of various cohorts of patients. Patients in cohort 3 had progression or recurrence of UC following a platinum-containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy. The primary endpoint was overall response rate (ORR) and secondary endpoints included duration of response (DOR), progression-free survival (PFS) and overall survival. This interview took place at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium 2022 in San Francisco, CA.
Transcript (edited for clarity)
Thank you so much for having me. I’m very excited to be at ASCO GU 2022. I was very excited to present, on behalf of the co-investigators and co-authors, the results of the Cohort 3 of the phase two TROPHY-U-01 trial. This is a combination of sacituzumab govitecan (SG) and antibody drug conjugate against Trop-2 linked with SN-38, a metabolite of irinotecan, combined with anti-PD-1 pembrolizumab in patients with platinum refractory, advanced urothelial cancer, immunotherapy naive, in the second line setting...
Thank you so much for having me. I’m very excited to be at ASCO GU 2022. I was very excited to present, on behalf of the co-investigators and co-authors, the results of the Cohort 3 of the phase two TROPHY-U-01 trial. This is a combination of sacituzumab govitecan (SG) and antibody drug conjugate against Trop-2 linked with SN-38, a metabolite of irinotecan, combined with anti-PD-1 pembrolizumab in patients with platinum refractory, advanced urothelial cancer, immunotherapy naive, in the second line setting.
This combination showed an objective response rate of 34% in a very difficult to treat population. These are patients with platinum refractory disease, and many of them had early progression on platinum. The median time between the last platinum chemotherapy regimen dose and trial screening was 1.6 months only, so very early platinum progressors, so difficult to treat population.
Despite that the objective response rate of 34%, one CR, 13 PRs and additionally 11 patients with stable disease as best response. We have a 61% clinical benefit rate, and 63% of patients had reduction in the tumor burden in the scans, so significant improvement there, radiologically.
In the safety profile, we show that the combination is feasible, it’s manageable. The most common treatment related adverse events included diarrhea. Most of them was grade 1, grade 2, but we had about 20% at grade 3 for diarrhea. But overall we’re able to manage those patients, most of them as outpatient with anti-diarrhea medications, as well as hydration education. And we saw some bone marrow suppression. We have 12 patients, if I remember correctly, with growth factor utilization, and if we increase the growth factor utilization, we may reduce the chance of neutropenia. For patients; 10% had febrile neutropenia, and none of them had prior use of growth factor support. Other adverse events included anemia, fatigue, but overall, the combination was manageable, feasible and sought promising antitumor activity.
I think it merits further investigation in this difficult to treat platinum refractory population, as well as in early lines of therapy. So not practice changing changing yet, but definitely supports further evaluation of this combination of sacituzumab govitecan plus pembrolizumab.
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