Erdafitinib, EV Combination Shows Antitumor Activity in mUC With FGFR2/3 Alterations

An early-stage clinical trial highlights the promising antitumor activity resulting from erdafitinib plus enfortumab vedotin (EV) following platinum-based chemotherapy and PD-1/PD-L1 inhibitors for metastatic urothelial carcinoma (mUC) with FGFR2/3 genetic alterations.

Preliminary results were presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Previous research suggests that the activity of EV is not compromised by FGFR2/3 genetic alterations. Erdafitinib and EV have different mechanisms of action, and toxicities are mostly nonoverlapping, thus providing a rationale for evaluating the feasibility of the combination in patients with mUC and FGFR2/3 alterations.

Rohit K. Jain, MD, MPH, and colleagues designed a single-arm, multicenter, dose-escalation and expansion study to evaluate the combination of erdafitinib plus EV for safety, tolerability, pharmacokinetics, and antitumor activity in patients with mUC harboring somatic FGFR2/3 genetic alterations who have progressed after platinum-based chemotherapy and/or PD-1/PD-L1 inhibitors.

The ongoing dose-escalation phase seeks to identify the maximum tolerable dose and recommended phase 2 dose of EV, at dose levels of 1 mg/kg and 1.25 mg/kg, in combination with erdafitinib (8 mg on days 1, 8, and 15) for 28 days.

As of the data cutoff, Dr. Jain and colleagues have enrolled 8 patients and finished the first 28-day cycle; 6 of these patients received 1 mg/kg (maximum dose, 100 mg; DL1) and 2 patients received 1.25 mg/kg (maximum dose, 125 mg; DL2).

The most commonly observed treatment-related adverse events (TRAEs) included hyperphosphatemia (88%), mucositis (88%), hypercalcemia (75%), high aspartate transaminase (75%), hand-foot syndrome (75%), peripheral neuropathy (75%), alopecia (63%), diarrhea (63%), hypoalbuminemia (63%), and hypomagnesemia (63%). Grade 3 TRAEs included hand-foot syndrome (50%), anemia (17%), rash (17%), anorexia (17%), and paronychia (17%).

Researchers noted that 1 patient developed grade 4 Stevens-Johnson syndrome related to EV, but subsequently improved. All 8 patients are evaluable for response, and best response is partial response in all.

“Combination erdafitinib plus EV is feasible and preliminarily exhibits antitumor activity,” researchers concluded. “Dose escalation is ongoing to identify the maximum tolerated dose or recommended dose for expansion of the trial.”