START Madrid-FJD, Fundación Jiménez Díaz University Hospital, Madrid, Spain
Victor Moreno , Yohann Loriot , Begona Pérez Valderrama , Carmen Beato , Yann-Alexandre Vano , Mark T. Fleming , Ignacio Duran , Salvatore Siena , Jaszianne A. Tolbert , Anne OHagan , Sydney Akapame , Yvonne Y. Lau , Lionnel Geoffrois , Scott T. Tagawa , Begona Mellado , Arlene O. Siefker-Radtke
Background: ERDA, an oral pan-FGFR inhibitor, is approved by the US FDA for pts with metastatic urothelial carcinoma (mUC) with susceptible FGFR3/2 gene alterations and progressed after ≥1 line of prior platinum-containing chemotherapy (PCC).1 CET, an IgG4, binds to anti-programmed cell death proteins (PD-1) and has shown activity in solid tumors.2 ERDA+CET may demonstrate complementary mechanisms as neoantigen release by ERDA may prime the tumor microenvironment for response. NORSE is a phase 1b/2 study to evaluate ERDA+CET in pts with mUC. Methods: Adult mUC pts with specific FGFR alterations who have progressed after ≥1 prior systemic therapy and no prior FGFR or PD-1/PD(L)-1 inhibitors enrolled in 3 dose levels (DL) of ERDA (DL1: 6 mg, DL2A: 8 mg, DL2: 8 mg with uptitration [UPT] to 9 mg) + CET (IV, 240 mg). Cohorts enrolled until dose limiting toxicity (DLT) or RP2D was identified. Primary endpoints: DLT and adverse events (AEs). Results: Of 15 pts (DL1: 4, DL2A: 3, DL2: 8), 11 continued on treatment at the time of the data cut. 14/15 pts experienced AEs; 3 experienced serious unrelated AEs (urinary tract infection, urosepsis, and large intestinal obstruction) all in DL1, 2 led to death; 10 experienced Grade >3 AEs and 2 experienced AEs of special interest, considered related to ERDA (Table). No DLTs were observed in any cohorts, 8 mg with UPT + CET was established as the RP2D. At data cut-off, investigator-assessed best overall response rate (CR+PR+uCR+uPR) in pts treated with the RP2D was 71% and disease control rate was 100% for RECIST 1.1 evaluable pts (n=7). Conclusions: 8 mg ERDA with UPT+240 mg CET was well tolerated and established as the RP2D. The combination of ERDA+CET is being further explored in the ongoing randomized phase 2 study in first-line cisplatin-ineligible mUC pts (NCT03473743). Clinical trial information: 2017-001980-19.
AEs, n (%) | DL1 | DL2A | DL2 |
---|---|---|---|
Grade ≥ 3 | 3 (75) | 2 (67) | 5 (63) |
Stomatitis | 1 (25) | 0 | 2 (25) |
AEs of special interest | 0 | 1 (33) | 1 (13) |
Central Serous Retinopathy | 0 | 1 (33) | 1 (13) |
1. Loriot Y et al. NEJM. 2019;381:338-48 2. 10.1200/JCO.2019.37.8_suppl.31
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