Posted: Wednesday, March 30, 2022
Rohit K. Jain MD, MPH, of Moffitt Cancer Center, Tampa, Florida, and colleagues plan to conduct a phase Ib trial of the FGFR inhibitor erdafitinib combined with the antibody-drug conjugate enfortumab vedotin-ejfv in patients with metastatic urothelial carcinoma harboring FGFR2/3 gene aberrations. Presented during the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium (Abstract TPS595), this in-process study is an attempt to identify an effective way to improve outcomes of patients who experience disease progression with platinum-based chemotherapy and PD-L1 inhibitors.
“Tubulin antagonists induce a G2-M cell-cycle block, [whereas] FGFR inhibitors cause a G1 block, with studies suggesting that their combination may be additive or synergistic,” the study authors explained. “Retrospective studies suggest that the activity of enfortumab vedotin is not compromised by somatic FGFR2/3 genetic alterations. Hence, there is rationale to evaluate the feasibility of the combination of enfortumab vedotin and erdafitinib, to overcome the difficulties of resistance and sequencing these agents in patients with [these mutations].”
This phase Ib, single-arm, multicenter study plans to enroll up to 30 patients with metastatic urothelial carcinoma harboring FGFR2/3 mutations who experience disease progression after treatment with a PD-L1 inhibitor and platinum-based therapies. Participants will be required to have an Eastern Cooperative Oncology Group performance status of 0 to 2, a predominant urothelial component, neuropathy of grade 1, and no other ophthalmologic conditions.
Primary endpoints of this study include feasibility and identification of a recommended phase II dose; secondary endpoints include duration of response, objective response rate, overall survival, and progression-free survival. The dose-escalation phase will include no more than 18 individuals with a 3 + 3 design, followed by a dose-expansion cohort of 12 individuals. During the dose-expansion phase, dose-limiting toxicities will be evaluated using sequential Bayesian toxicity monitoring. Additionally, exploratory biomarker analyses will be performed at baseline and upon disease progression to evaluate association with response as well as resistance pathways.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.