Abstract 752P
Background
ERDA (an oral pan-FGFR inhibitor) plus CET (an immunoglobulin G4 monoclonal antibody specific for programmed death protein 1 [PD-1]) showed promising activity in the NORSE study (Moreno ASCO GU 2020, abst. 511). We present updated results from the phase 1b/2 NORSE study (NCT03473743).
Methods
Adult pts with mUC and specific FGFR alterations who progressed after ≥ 1 prior systemic therapy and had no prior FGFR therapy/PD-(L)1 inhibitors received 240 mg CET intravenously + 1 of 3 ERDA doses (DL1: 6 mg, DL2A and DL2B: 8 mg, DL2: 8 mg with uptitration to 9 mg [Upt]). In DL2B, CET was started at Cycle 2 Day 1. Dose escalation was allowed if no pt in a dose cohort had a dose-limiting toxicity (DLT) and continued until recommended phase 2 dose (RP2D) was identified. Primary end points were DLT and adverse events (AEs) in phase 1b and were objective response rate (ORR) and AEs in phase 2. Data from the phase 1 portion of the study are presented.
Results
RP2D was established as 8 mg Upt + 240 mg CET. At data cutoff (April 2020), treatment was ongoing for the majority (68%) of 22 treated pts. Treatment-emergent AEs (TEAEs) and treatment-related AEs (TRAEs) were reported in most pts (91% each; Table). Three pts had serious TRAEs. Two pts died due to TEAEs (both DL1); neither was related to treatment. Three (14%) pts had grade 2 events of central serous retinopathy, a known class effect of FGFR inhibitors. Confirmed ORR in 11 evaluable pts treated at the RP2D was 55% (Table) and disease control rate (including unconfirmed complete response, unconfirmed partial response, and stable disease) was 100%. Table: 752P
| Summary of ORR, TEAEs, TRAEs, and TEAEs of Special Interest | |||||
| n (%) | DL1 (n = 4) | DL2A (n = 3) | DL2B (n = 3) | DL2 (n = 12) | Total (N = 22) |
| ORR, n/n evaluable (%) | 2/4 (50) | 2/3 (67) | 1/3 (33) | 6/11 (55) | 11/21 (52) |
| TEAEs | 4 (100) | 3 (100) | 2 (67) | 11 (92) | 20 (91) |
| Grade 3-4 TEAEs | 3 (75) | 2 (67) | 1 (33) | 5 (42) | 11 (50) |
| Serious TEAEs | 3 (75) | 0 | 0 | 4 (33) | 7 (32) |
| TRAEs | 4 (100) | 3 (100) | 2 (67) | 11 (92) | 20 (91) |
| Grade 3-4 TRAEs | 1 (25) | 2 (67) | 1 (33) | 5 (42) | 9 (41) |
| Serious TRAEs | 0 | 0 | 0 | 3 (25) | 3 (14) |
| Most common grade 3-4 AE, stomatitis | 1 (25) | 0 | 0 | 2 (17) | 3 (14) |
| AE of special interest, central serous retinopathy | 0 | 1 (33) | 0 | 2 (17) | 3 (14) |
Conclusions
The combination of ERDA and CET is tolerable and associated with promising antitumor activity. ERDA 8 mg Upt + CET 240 mg was established as RP2D. ERDA + CET is being further explored in the ongoing randomized phase 2 portion of this study as first-line treatment for pts ineligible for cisplatin.
Clinical trial identification
NCT03473743.
Editorial acknowledgement
Sally Hassan, PhD, CMPP, of Parexel International provided editorial assistance for this abstract.
Legal entity responsible for the study
Janssen Research & Development, LLC.
Funding
Janssen Research & Development, LLC.
Disclosure
A.O. Siefker-Radtke: Advisory/Consultancy: Merck Bavarian Nordic Seattle Genetics Genentech Janssen Mirati AstraZeneca Nektar Therapeutics Pfizer; Speaker Bureau/Expert testimony: Janssen. Y. Loriot: Honoraria (self): Roche, Astellas, Janssen, Seattle Genetics, Astra-Zeneca, Bristol Myers Squibb, MSD, Pfizer, Sanofi, Ipsen; Research grant/Funding (institution), Clinical Trial: Roche, Bristol Myers squibb, Astra-Zeneca, MSD, Pfizer, Seattle Genetics, Astellas, Janssen, Clouis, Incyte Sanofi; Research grant/Funding (institution), Research Grant: MSD, Sanofi, Janssen. S. Siena: Advisory/Consultancy: Amgen, Bayer, Bristol Myers Squibb, CheckMab, Clovis, Daiichi-Sankyo, Merck, Roche-Genentech, Seattle Genetics. C. Beato: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche. M.A. Climent Duran: Research grant/Funding (institution): AstraZeneca, Roche; Advisory/Consultancy: Roche, BMS, MSD, Pharmacyclycs, Jansen, Ipsen, Novartis; Honoraria (self): Roche, BMS, MSD, Jansen, Ipsen, Novartis, Astellas; Travel/Accommodation/Expenses: Ipsen, Astra-Zeneca. I. Duran: Research grant/Funding (self): Astra-Zeneca, Roche; Advisory/Consultancy, Officer/Board of Directors: Roche, Bristol Myers Squibb, MSD, Pharmacyclycs, Jansen, Ipsen, Novartis; Honoraria (self): Roche, Bristol Myers Squibb, Jansen, Ispen, Novatris, Astellas; Travel/Accommodation/Expenses: Ispen, Astra-Zeneca. S.T. Tagawa: Research grant/Funding (institution): Sanofi, Medivation, Astellas, Janssen, Amgen, Progenics, Dendreon, Lilly, Genentech, Newlink, BMS, Inovio, AstraZeneca, Immunomedics, Aveo, Rexahn, Atlab, Boehringer Ingelheim, Millennium, Bayer, Merck, Abbvie, Karyopharm, Endocyte, Clovis, Seattle Geneti; Honoraria (self): Sanofi, Medivation/Astellas, Dendreon, Janssen, Genentech, Bayer, Endocyte, Eisai, Immunomedics, Karyopharm, Abbvie, Tolmar, Seattle Genetics, Amgen, Clovis, QED, Pfizer, AAA/Novartis, Genomic Health, POINT Pharma, Ambrx; Non-remunerated activity/ies: Atlab Pharma, Telix Pharma, Phosplatin Therapeutics, Amgen. L. Geoffrois: Honoraria (self), Travel/Accommodation/Expenses: Ispen; Honoraria (self): Bristol Myers Squibb; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self): MSD. B. Mellado: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche; Advisory/Consultancy, Research grant/Funding (self): Astellas; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Sanofi. A.P. Lykov: Research grant/Funding (institution), Full/Part-time employment: State Autonomous Healthcare Institution Multidisciplinary Clinical Medical Center. S. Akapame: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. A. O'Hagan: Full/Part-time employment: Jansen; Shareholder/Stockholder/Stock options: Johnson & Johnson. M. Tammaro: Full/Part-time employment: Janssen Pharmaceuticals. S. Mosher: Advisory/Consultancy: Janssen Pharmaceuticals. T.W. Kang: Full/Part-time employment: Chonnam National University Medical School, Chonnam National University Hospital; Advisory/Consultancy: Janssen Pharmaceuticals, Astellas Pharma; Research grant/Funding (self): Alvogen Korea. V. Moreno: Advisory/Consultancy: Bristol Myers Squibb, Bayer. All other authors have declared no conflicts of interest.