Phase 1 DAD Trial: Sacituzumab Govitecan Plus Enfortumab Vedotin Safe, Feasible for mUC

Dr. Bradley McGregor, of the Dana-Farber Cancer Institute, presents results from the phase 1 double antibody-drug conjugate (DAD) trial at the European Society for Medical Oncology Congress 2023.

As antibody-drug conjugates are a mainstay treatment for patients with metastatic urothelial carcinoma (mUC), the new phase 1 trial analyzed the safety and efficacy of sacituzumab govitecan plus enfortumab vedotin as a second-line or higher therapy in that patient population.

Patients enrolled in the trial were diagnosed with mUC and progressed on platinum and immunotherapy or were cisplatin ineligible and received 1 line of therapy. Each patient had an Eastern Cooperative Oncology Group performance status of 1 or higher.

Sacituzumab govitecan plus enfortumab vedotin was administered to patients on days 1 and 8 of a 21-day cycle until progression or unacceptable toxicity. To determine the feasibility and safety of combining sacituzumab govitecan with enfortumab vedotin, doses were adjusted based on the occurrence of dose-limiting toxicities (DLTs) during cycle (C) 1 and the total number of patients treated at 4 prespecified dose levels (DL) using a Bayesian optimal interval design. Adverse events (AE) were assessed using Common Terminology Criteria for Adverse Events, version 5.0.

A total of 24 patients (9 on DL1, 9 on DL2, 6 on DL3) were enrolled in the trial from May 2021 to April 2023. At the cutoff in May 2023, 23 patients were evaluable for DLT assessment, while 1 patient in the DL3 group never began therapy. The median patient age was 69 years, and 22 patients received 2 or more lines of therapy.

After 2 patients in the DL1 group experienced febrile neutropenia, treatment with prophylactic granulocyte colony-stimulating factor was permitted and administered to 18 patients. Grade 3 or higher AEs at any DL occurred in 70% of patients, and 1 grade 5 AE (pneumonitis possibly related to enfortumab vedotin) occurred during C2 of DL3.

Among the 21 patients who were evaluable for response, the objective response rate (ORR) was 71% (15/21; 90% CI, 51-87), with 2 complete and 13 partial responses; 2 patients had progressive disease. With a median follow-up of 11.9 months, 11 of 15 responses are ongoing from 1.1+ to 21.6+ months.

The combination of sacituzumab govitecan plus enfortumab vedotin was found to be safe, with an ORR of 71% in patients with mUC. Further trial cohorts in the treatment-refractory and treatment-naïve settings are in development, and triplet therapy with immunotherapy is being explored.