Memorial Sloan Kettering Cancer Center, New York, NY
Jonathan E. Rosenberg , Srikala S. Sridhar , Jingsong Zhang , David C. Smith , Joseph D. Ruether , Thomas W. Flaig , Joaquina Celebre Baranda , Joshua Michael Lang , Elizabeth R. Plimack , Randeep S. Sangha , Elisabeth I. Heath , Jaime R. Merchan , David I. Quinn , Sandy Srinivas , Matthew I. Milowsky , Chunzhang Wu , Elaina M Gartner , Amal Melhem-Bertrandt , Daniel Peter Petrylak
Background: Enfortumab vedotin (EV) is an antibody?drug conjugate that delivers MMAE, a microtubule disrupting agent, to tumors expressing Nectin-4, a protein found on most urothelial cancers. Preliminary results of the EV-101 study (NCT02091999) suggest EV is active and tolerable. Methods: Patients with mUC treated with ≥1 prior chemotherapy, or those ineligible for cisplatin, received EV 1.25 mg/kg on Day 1, 8, and 15 every 28 day cycle. The primary objective was tolerability; antitumor activity (ORR per RECIST v1.1), assessed every 8 wk, was a secondary objective. Results: As of14 Sept 2018,112 pts with mUC received EV with a median follow up of 13.4 mo. Bladder was the primary tumor site in 86 pts (77%) and 33 (29.5%) had liver metastases (LM). Nearly all pts received prior platinum chemotherapy; 89 (79.5%) received prior anti-PD(L)1. EV was well tolerated; fatigue (53%), alopecia (46%), and decreased appetite (42%) were the most commonly reported treatment-related AEs (TRAEs). Anemia (8%), hyponatremia (7%), UTI (7%), and hyperglycemia (6%) were the grade ≥3 AEs reported in ≥5% of pts regardless of attribution; 4 fatal TRAEs were reported (respiratory failure, urinary tract obstruction, diabetic ketoacidosis, multi-organ failure). Confirmed ORR was 42% (CR, n = 5; PR, n = 42). Among responders, median duration of response was 7.7 mo (95% CI 5.6, 9.6) and 23.4% of responses were ongoing with a median follow up of 11.3 mo. Estimated median PFS and OS were 5.4 mo (95% CI 5.1, 6.3) and 12.5 mo (95% CI 9.3, 16.1), respectively; OS at 1 yr was 51.8%. Similar results were seen in pts with prior anti-PD(L)1 and with LM (Table). Conclusions: Single-agent EV was generally well tolerated and provided encouraging response and survival data in a population with an unmet medical need including pts with LM, which is associated with poor prognosis. Phase 2 and 3 monotherapy studies as well as evaluation of combination therapies are ongoing. Clinical trial information: NCT02091999
Prior Anti-PD(L)1 (N = 89) | LM (N = 33) | |
---|---|---|
ORR, % (95% CI) | 42 (31.2, 52.5) | 36 (20.4, 54.9) |
DoR, median mo (95% CI) | 7.4 (4.2, 9.4) | 7.7 (3.7, --) |
PFS, median mo (95% CI) | 5.4 (5.1, 6.3) | 3.5 (1.6, 6.6) |
OS, median mo (95% CI) | 12.2 (8.5, 17.1) | 10.4 (6.4, 14.1) |
OS at 1 year, % (95% CI) | 51.6 (40.3, 61.8) | 42.0 (25.0, 58.0) |
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Abstract Disclosures
2018 ASCO Annual Meeting
First Author: Jonathan E. Rosenberg
2024 ASCO Gastrointestinal Cancers Symposium
First Author: Hendrik-Tobias Arkenau
2024 ASCO Genitourinary Cancers Symposium
First Author: Evangelia Vlachou
2024 ASCO Annual Meeting
First Author: Benedict J. Panizza