2359O - Phase III THOR study: Results of erdafitinib (erda) vs pembrolizumab (pembro) in pretreated patients (pts) with advanced or metastatic urothelial cancer (muc) with select fibroblast growth factor receptor alterations (FGFRalt)

Background

Erda is an oral pan-FGFR tyrosine kinase inhibitor approved to treat locally advanced or mUC in pts with susceptible FGFR3/2alt who have progressed after platinum-containing chemotherapy. FGFRalt tumors are enriched in luminal 1 subtype and may have limited clinical benefit from anti–PD-(L)1 treatment (tx). This cohort in the randomized, open-label phase 3 THOR study (NCT03390504) assessed erda vs pembro in pts with mUC naive to anti–PD-(L)1.

Methods

Pts ≥18 y with unresectable advanced/mUC with select FGFR3/2alt, ECOG PS 0-2, disease progression on 1 prior tx, and naive to anti–PD-(L)1 were randomized 1:1 to receive erda 8 mg QD with pharmacodynamically guided uptitration to 9 mg or pembro 200 mg Q3W. Primary end point: overall survival (OS). Secondary end points: progression-free survival (PFS), objective response rate (ORR), safety.

Results

At 15 Jan 2023 data cutoff, intent-to-treat set (median follow-up 33.2 mo) comprised 175 pts in erda and 176 in pembro arm. The primary end point was not met, with no statistically significant difference in OS between tx arms (Table). Erda had numerically longer PFS and numerically higher ORR but shorter duration of response. Most common tx-related adverse events (TRAEs) of any grade: hyperphosphatemia (73%), stomatitis (45%), diarrhea (45%), and dry mouth (35%) with erda; pruritus (12%), asthenia (10%), hypothyroidism (10%), and fatigue (10%) with pembro. Gr 3-4 TRAEs and serious TRAEs occurred in 43% and 13% in erda and 12% and 10% in pembro arm, respectively. TRAEs leading to death occurred in 0 pts in erda and 3 (2%) in pembro arm. 15% of pts discontinued erda and 5% discontinued pembro due to TRAEs. Table: 2359O

All data are value (95% CI). ^aNominal p estimate, due to primary end point not being met.

Conclusions

Erda and pembro had similar OS in this anti–PD-(L)1 naive, FGFRalt mUC population, with erda showing a numerically longer PFS and numerically higher ORR rate. Toxicities were manageable with dose modifications.

Clinical trial identification

NCT03390504.

Editorial acknowledgement

Medical writing assistance was provided by Nicolisha Narainpersad, PhD, of Parexel, and was funded by Janssen Global Services, Llc.

Legal entity responsible for the study

Janssen Research & Development.

Funding

Janssen Research & Development.

Disclosure

A.O. Siefker-Radtke: Financial Interests, Institutional, Research Grant: Janssen, asilea Pharmaceutica, Bristol Myers Squibb, Janssen, Merck, Millennium, and Nektar; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: AstraZeneca, Bavarian Nordic, Basilea, Bristol Myers Squibb, Genentech, G1 Therapeutics, Gilead, Ideeya Biosciences, Immunomedics, Janssen, Loxo, Merck, Mirati, Nektar Therapeutics, Seattle Genetics, and Taiho; Financial Interests, Personal, Invited Speaker: Janssen. N. Matsubara: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: Janssen, MS, Eli Lilly; Financial Interests, Institutional, Research Grant: Janssen ,AstraZeneca, Bayer, MSD, Taiho, Astellas, Amgen, Eisai, Eli Lilly, Takeda, Pfizer, Seagen, Chugai, Abbvia, Novartis. S.H. Park: Financial Interests, Personal, Other, Honoraria: Merck, Pfizer, Ono Pharma Korea; Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen; Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme Llc. R.A. Huddart: Financial Interests, Personal, Other, Personal Fees: Aspen Parkside Hospital; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: Aspen Parkside Hospital; Financial Interests, Personal, Other, Honoraria: Janssen Oncology; Financial Interests, Personal, Other, Travel Reimbursment: Janssen Oncology, Roche/Genentech, MSD Oncology, and Nektar; Financial Interests, Personal, Non-financial benefits: Merck Sharp & Dohme, Roche, Bristol Myers Squibb, and Janssen; Financial Interests, Personal, Other, Patents: Janssen; Financial Interests, Personal, Leadership Role: Cancer Clinic London Limited Liability Partnership. E.F. Burgess: Financial Interests, Personal, Research Grant: Pfizer, Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Exelixis, Bayer; Financial Interests, Personal, Stocks/Shares: Exelixis, Becton Dickinson, Calithera Biosciences, Gilead Sciences, Medtronic, Clovis Oncology, and Macrogenics. M. Ozguroglu: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: Astellas, Sanofi; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Other, Meeting Support: Regeneron; Financial Interests, Personal, Leadership Role: AstraZeneca, Bayer. B. Perez Valderrama: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Parma; Financial Interests, Personal, Other, Honoraria: Pierre Fabre; Financial Interests, Personal, Other, Travel Reimbursment: Janssen-Cilag and Pfizer. S. Triantos, S. Akapame, Y. Kean, S. Mukhopadhyay: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. K. Deprince: Financial Interests, Personal, Other, Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. Y. Loriot: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: Loxo/Lilly, Pfizer/EMD Serono, Roche, Taiho Pharmaceutical, Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Immunomedics, Janssen ; Financial Interests, Institutional, Speaker, Consultant, Advisor, Consultancy Fees: MSD Oncology ; Financial Interests, Personal, Other, Travel reimbursement: AstraZeneca, Janssen Oncology, MSD Oncology, and Roche; Financial Interests, Institutional, Research Funding: Astellas Pharma, AstraZeneca, Basilea, Bristol Myers Squibb, Exelixis, Gilead Sciences, Incyte, Janssen Oncology, Merck KGaA, MSD Oncology, Nektar, Pfizer, Roche, Sanofi, and Taiho Pharmaceutical.