Erdafitinib (ERDA) vs ERDA plus cetrelimab (ERDA+CET) for patients (pts) with metastatic urothelial carcinoma (mUC) and fibroblast growth factor receptor alterations (FGFRa): Final results from the phase 2 Norse study.

person Arlene O. Siefker-Radtke Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Arlene O. Siefker-Radtke, Thomas Powles, Victor Moreno, Taek Won Kang, Irfan Cicin, Angela Girvin, Sydney Akapame, Spyros Triantos, Anne O'Hagan, Wei Zhu, Meggan Tammaro, Yohann Loriot

Authors person Arlene O. Siefker-Radtke Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Arlene O. Siefker-Radtke, Thomas Powles, Victor Moreno, Taek Won Kang, Irfan Cicin, Angela Girvin, Sydney Akapame, Spyros Triantos, Anne O'Hagan, Wei Zhu, Meggan Tammaro, Yohann Loriot Organizations Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St. Bartholomew's Hospital, London, United Kingdom, START Madrid-FJD, Fundación Jiménez Díaz, University Hospital, Madrid, Spain, Department of Urology, Chonnam National University Medical School, Gwangju, South Korea, Department of Medical Oncology, Trakya University Faculty of Medicine, 22030, Edirne, Turkey, Janssen Research & Development, Spring House, PA, Janssen Research & Development, Raritan, NJ, Gustave Roussy and Paris Saclay University, Villejuif, France Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Janssen Research & Development Background: First-line (1L) therapy for cisplatin (cis)-ineligible pts with mUC remains an unmet need and includes alternative chemotherapy or anti-PD-(L)1 monotherapy for PD-L1 positive tumors. FGFRa tumors are enriched for the luminal 1 subtype with lower immune cell infiltrate and potential lower benefit from anti-PD-(L)1 monotherapy. We studied ERDA+CET in 1L, FGFRa, mUC to determine the potential impact in this setting (NCT03473743). Methods: Pts aged ≥ 18 y with mUC, susceptible FGFRa and measurable disease (no prior systemic therapy for mUC, cis-ineligible) were randomized 1:1 to once-daily ERDA 8 mg (with pharmacodynamically guided uptitration (UpT) to 9 mg) or ERDA 8 mg (no UpT) + IV CET 240 mg every 2 weeks (wks) at cycles 1-4 and 480 mg every 4 wks thereafter. Primary endpoints were investigator-assessed overall response rate (ORR) per RECIST 1.1 and safety; secondary included duration of response (DOR), time to response (TTR), progression free survival (PFS) and overall survival (OS). There were no pre-planned statistical comparisons between treatment arms. Results: As of the data cutoff, 87 pts were randomized and treated; 44 to ERDA+CET and 43 to ERDA: median age was 69 vs 72 y; visceral metastases were present in 60.0 vs 63.6%. Median follow-up time was 14.2 months (mo). ORR for ERDA+CET was 54.5% with 6 (13.6%) CRs and 12 mo OS 68%. 11/24 responders were ongoing. ORR for ERDA was 44.2% with 1 CR and 12 mo OS 56%. 9/19 responders were ongoing. 4 pts in each arm were PD-L1 positive. 3/4 (75%) PD-L1 positive pts responded to ERDA+CET vs 0 for ERDA. The most frequent treatment-emergent AEs (any grade) were hyperphosphatemia (68.9 vs 83.7%), stomatitis (59.1 vs 72.1%) and diarrhea (45.5 vs 48.8%) for ERDA+CET and ERDA respectively. Grade ≥3 treatment-related AEs occurred in 45.5 (ERDA+CET) and 46.5% (ERDA) of pts. There was one CET-related death in ERDA+CET secondary to pulmonary failure. Conclusions: Combination ERDA+CET demonstrated clinically meaningful activity and was well tolerated. These results, in 1L cis-ineligible pts, support previously described activity of ERDA monotherapy in FGFRa mUC. The safety profile was consistent with the known profile for ERDA and CET with no additive toxicity for the combination. Clinical trial information: NCT03473743. ERDA+CET (n=44) ERDA (n=43) ORR, % (95% CI) 54.5 (38.8, 69.6) 44.2 (29.1, 60.1) Confirmed CR, n (%) 6 (13.6) 1 (2.3) DCR, % (95% CI) 79.5 (64.7, 90.2) 88.4 (74.9, 96.1) Median DOR (95% CI), mo 11.10 (8.77, NE) 9.72 (4.60, NE) Median PFS (95% CI), mo 10.97 (5.45, 13.63) 5.62 (4.34, 7.36)