Sacituzumab govitecan (IMMU-132) for patients with pretreated metastatic urothelial uancer (UC): interim results

Abstract

Background: Advanced UC is most often seen in senior pts, in whom age-related complications such as renal dysfunction and poor performance status (PS) preclude $50% from receiving standard first-line cisplatin treatment. In the phase 2 KEYNOTE-052 trial (NCT02335424), first-line pembro had clinically meaningful antitumor activity (ORR, 24%) and was well tolerated in cisplatin-ineligible pts with UC. Results from the subgroup of pts who were considered senior (!65 y or ! 75 y) and had ECOG PS 2 are presented. Methods: Pts were cisplatin ineligible and had advanced UC, measurable disease (per RECIST v1.1), ECOG PS 0-2, and no prior systemic chemotherapy. Pts received pem-bro 200 mg Q3W. Radiographic imaging was performed at wk 9, then Q6W for the first year, and Q12W thereafter. The primary end point was ORR (RECIST v1.1, independent radiology review). Results: Of 370 pts, 302 (82%) were !65 y, 179 (48%) were !75 y, 120 (32%) were !65 y with ECOG PS 2, and 78 (21%) were !75 y with ECOG PS 2. Median follow-up was 5 mo. ORR (95% CI) was similar to that reported in the overall study population regardless of age cutoff (Table). Poor PS did not impact ORR in senior pts (Table). 6-mo PFS rates were consistent across senior groups (Table). 64% (!65 y), 66% (!75 y), 58% (!65 and ECOG PS 2), and 64% (!75 y and ECOG PS 2) of pts experienced treatment-related AEs. 16% of pts !65 and !75 y and 17% of pts !65 and !75 y with ECOG PS 2 experienced grade !3 treatment-related AEs. Conclusions: Results from subgroup analyses of senior pts with poor PS in KEYNOTE-052 confirm that first-line pembro elicits clinically meaningful responses consistent with the overall study population. Pembro is well tolerated in cisplatin-ineligible pts with UC, including those who are senior with poor PS. Background: Pts with metastatic UC have limited therapy options. Immune checkpoint inhibitors (CPI) are now given to patients with advanced UC, but only about 25% respond. We are studying the safety and efficacy of sacituzumab govitecan (IMMU-132), an anti-Trop-2/SN-38 antibody-drug conjugate, in pts with UC refrac-tory to other therapies. Methods: In this phase I/II study (NCT01631552), pts with metastatic UC who progressed after !1 prior systemic therapy were treated with IMMU-132 at 10 mg/kg on days 1 and 8 of 21-day cycles, until progression or unacceptable toxicity. All intention-to-treat (ITT) pts, including those who relapsed/progressed after CPI therapy, are evaluated for safety, ORR by RECIST 1.1 (confirmed PR/CR), PFS, and OS. Response-evaluable (RE) pts received ! 2 doses and ! 1 post-baseline CT (RECIST 1.1) assessment. Results: 41 pts (39M/2F; median age 68 y, range 50-91) were enrolled (RE ¼ 36); ECOG 0/1: 31%/69%; median of 3 (range 1-6) prior therapies, including 34/41 platinum and 15/41 CPI regimens. Metastatic sites: lymph node 68%, lungs 54%, liver 32%, bone 27%; overall visceral disease, 31/41 (76%). Pts received a median of 12 (range 1-58) doses. ORR in the ITT population was 34% [14/41 (1 CR, 13 PR); ORR was 39% in the RE group, including 5/13 (39%) with liver mets]; 14 SD (39%); 8 PD (20%), and 5 inevaluable. In responders, 13/14 had prior platinum, 8/14 (57%) !3 prior therapies, and 4 prior CPI [4/13 in the RE group (31%), where IMMU-132 was !4 th line of therapy in 11/13 pts]. Median time to response: 1.9 mos. Median duration of response: 12.9 mos (95%CI, 5.1-12.9), with 8/14 continuing therapy. Clinical benefit rate (CRþPRþSD!6 mos) is 44%; 56% for SD ! 4 mos. In the 41 ITT pts, median PFS and OS are 7.2 (95% CI, 5.0-10.7) and 15.5 mos (95% CI, 8.9-17.2), respectively. Grade !3 adverse events !5% were 28% neutropenia, 9% febrile neutropenia, 9% fatigue, 9% anemia, 6% diarrhea. Conclusions: With an ITT ORR of 34%, PFS of 7.2 mos, OS of 15.5 mos, and duration of response of 12.9 mos in 41 unselected pts with advanced pretreated UC (median of 3 prior therapies), these interim results show IMMU-132 is a promising agent in pts relapsed/refractory to chemotherapy and immune checkpoint inhibitors.