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BALVERSA® (erdafitinib)

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BALVERSA - NORSE Study

Last Updated: 04/03/2026

Click on the following links to related sections within the document: Study Design/Methods and Results.
Note: For information regarding this ongoing clinical trial, including a detailed listing of eligibility criteria, please visit https://clinicaltrials.gov/ct2/show/NCT03473743.
Abbreviations: C, cycle; CI, confidence interval; DCR, disease control rate; DL, dose level; DLT, dose-limiting toxicity; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; FGFR, fibroblast growth factor receptor; IV, intravenous; mUC, metastatic urothelial carcinoma; ORR, overall response rate; OS, overall survival; PD-1, programmed cell death receptor-1; PD-L1, programmed cell death ligand-1; PFS, progression-free survival; PK, pharmacokinetics; PO, orally; PO₄, phosphate; Q2W, every 2 weeks; Q2W, every 2 weeks; Q4W, every 4 weeks; QD, daily; R, randomization; RP2D, recommended phase 2 dose; TRAE, treatment-related adverse event; UC, urothelial carcinoma.
^aClinicalTrials.gov (NCT03473743).¹ ^bSiefker-Radtke (2020).² ^cMoreno (2020).³ ^dPowles (2021).⁴ ^eLoriot (2026).⁵^fPer serum phosphate levels.^gOf the total 87 patients, 1 in the erdafitinib arm (n=43) and 5 in the erdafitinib plus cetrelimab arm (n=44) were inevaluable.

CLINICAL STUDY

NORSE Study

The NORSE study (BLC2002; NCT03473743) is evaluating the recommended phase 2 dose (RP2D), pharmacokinetics (PK), efficacy, and safety of BALVERSA plus cetrelimab, and for BALVERSA in combination with cetrelimab and platinum (cisplatin and carboplatin) chemotherapy, in patients with locally advanced or metastatic urothelial carcinoma (mUC) and selected fibroblast growth factor receptor (FGFR) alteration.¹^-⁵

Study Design/Methods

Phase 1b/2, open-label, noncomparative, multicenter study
Enrolled patients (N=125) included patients with metastatic or locally advanced urothelial carcinoma (UC), FGFR3/2 alterations, and who were cisplatin-ineligible.
The phase 1b dose-escalation study evaluated 3 dosing levels of BALVERSA orally (PO) daily with a fixed dose of cetrelimab 240 mg intravenous (IV) every 2 weeks (Q2W) in patients who had received ≥1 prior therapy to identify the RP2D for further evaluation in the phase 2 dose-expansion study (see Figure: NORSE Study Design - BALVERSA Combination With Cetrelimab Cohorts).

NORSE Study Design - BALVERSA Combination With Cetrelimab Cohorts¹^-⁵

Abbreviations: AE, adverse event; CrCl, creatinine clearance; CR, complete response; DCR, disease control rate; DL, dose level; DLT, dose-limiting toxicity; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; FGFR, fibroblast growth factor receptor; IV, intravenous; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; ORR, overall response rate; OS, overall survival; PD, progressive disease; PD-1, programmed cell death receptor-1; PD-L1, programmed cell death ligand-1; PD-L2, programmed cell death ligand-2; PFS, progression-free survival; PK, pharmacokinetics; PO, orally; PR, partial response; Q12W, every 12 weeks; Q2W, every 2 weeks; Q4W, every 4 weeks; Q6W, every 6 weeks; QD, daily; R, randomization; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; UC, urothelial carcinoma.
^aMolecular eligibility was confirmed using either central or local (tissue or blood) FGFR test results. Tumors were required to have at least 1 of the following fusions: FGFR2-BICC1, FGFR2-CASP7, FGFR3-TACC3 (v1 or v3), FGFR3-BAIAP2L1, or FGFR3 gene mutations R248C, S249C, G370C, or Y373C.
^bDefined as having ECOG PS 2 alone or ECOG PS 0-1 and meeting at least 1 of the following criteria: impaired renal function defined as calculated by Cockcroft-Gault (≥30 to <60 mL/min), grade ≥2 peripheral neuropathy, and grade ≥2 hearing loss.
^cPer serum phosphate levels.
^dORR was defined as proportion of patients who had investigator-assessed confirmed CR or PR per RECIST v1.1.
^eDCRwas defined as proportion of patients with CR or PR and SD.
^fDOR from initial documentation of a CR or PR to first documented evidence of PD or death, whichever was reported first.
^gTime to responsewas defined as time from randomization to initial documentation of CR or PR.
^hPFSwas defined as duration from random assignment until first documented evidence of PD or death, whichever was reported first.
ⁱOSwas defined as time from random assignment to death.

The study was planned to enroll approximately 90 patients.⁴
In the phase 2 study, patients were randomized 1:1 to receive⁴^,⁵:
- BALVERSA 8 mg PO daily with pharmacodynamically guided uptitration to 9 mg PO daily alone or
- BALVERSA 8 mg PO daily (without uptitration) in combination with cetrelimab 240 mg IV Q2W for cycles 1-4, then 480 mg IV every 4 weeks (Q4W) thereafter
Randomization was stratified by Eastern Cooperative Oncology Group performance status (ECOG PS; 0-1 vs 2).
The primary analysis was the end of the study, and no additional efficacy data were collected.
Patients continued to receive the study treatment and were allowed to continue in a long-term extension phase. Only serious adverse event (AE) data were collected during this time.

Results

There were 132 patients who met full study eligibility (for both parts 1 and 2 of the study), including those who were FGFR-positive.

Baseline Characteristics

Baseline characteristics of the patients from the phase 1b study are summarized in Table: Phase 1b: Baseline Disease Characteristics, Demographics, and Treatment Exposure.

Phase 1b: Baseline Disease Characteristics, Demographics, and Treatment Exposure²

Characteristic	DL1^a(n=4)	DL2A^b(n=3)	DL2B^c(n=3)	DL2^d(n=12)	Total (N=22)
Median treatment exposure, months (range)	5.3 (3-7)	8.3 (0-9)	5.1 (5-5)	5.5 (0-9)	5.5 (0-9)
Median age, years (range)	74 (64-79)	68 (57-75)	58 (51-65)	67 (31-73)	67 (31-79)
Sex, n (%)
Male	4 (100)	2 (67)	3 (100)	7 (58)	16 (73)
ECOG PS, n (%)
0	2 (50)	1 (33)	3 (100)	8 (67)	14 (64)
1	2 (50)	2 (67)	0	4 (33)	8 (36)
Presence of visceral metastases,^e n (%)	2 (50)	3 (100)	2 (67)	5 (42)	12 (55)
Number of prior systemic therapy lines,^f n (%)
0	0	0	0	1 (8)	1 (5)
1	4 (100)	2 (67)	3 (100)	7 (58)	16 (73)
2	0	1 (33)	0	4 (33)	5 (23)
Primary tumor location, n (%)
Lower tract	3 (75)	3 (100)	2 (67)	6 (50)	14 (64)
Upper tract	1 (25)	0	1 (33)	6 (50)	8 (36)
PD-L1 positive status,^g n (%)
Yes	0	0	0	4 (33)	4 (18)
No	1 (25)	1 (33)	0	2 (17)	4 (18)
Not available	3 (75)	2 (67)	3 (100)	6 (50)	14 (64)
Any FGFR alteration,^h n (%)	4 (100)	2 (67)	1 (33)	10 (83)	17 (77)
FGFR mutations (excluding fusions)	3 (75)	2 (67)	1 (33)	9 (75)	15 (68)
FGFR fusions (excluding mutations)	1 (25)	0	0	1 (8)	2 (9)
Abbreviations: DL, dose level; ECOG PS, Eastern Cooperative Oncology Group performance status; FGFR, fibroblast growth factor receptor; PD-L1, programmed cell death ligand-1; PO₄, phosphate. ^aDL1=BALVERSA 6 mg plus cetrelimab 240 mg. ^bDL2A=BALVERSA 8 mg (no uptitration) plus cetrelimab 240 mg. ^cDL2B=BALVERSA 8 mg with uptitration to 9 mg based on serum PO₄ levels plus cetrelimab 240 mg (cetrelimab started at cycle 2 day 1). ^dDL2=BALVERSA 8 mg with uptitration to 9 mg based on serum PO₄ levels plus cetrelimab 240 mg. ^eLung, liver, and bone. ^fIn phase 2, prior lines were for neo/adjuvant therapy. ^gPD-L1 expression level was assessed by immunohistochemistry (Dako 28.8) in tumor tissue provided at screening (PD-L1 positivity if Tumor Proportion Score ≥1%). ^hBased on central laboratory tissue testing, FGFR alteration status was not available for 3 patients at the time of this analysis; 2 patients enrolled using local and blood-based testing, respectively, but did not have FGFR alterations according to central laboratory tissue testing.

A total of 89 patients were randomly assigned in part 2 of the study (BALVERSA, n=44; BALVERSA plus cetrelimab, n=45). One patient from each group was not randomly assigned and not included in the treated analysis set.
Baseline characteristics of the patients from the phase 2 study are summarized in Table: Phase 2 Final Analysis: Baseline Disease Characteristics and Demographics.

Phase 2 Final Analysis: Baseline Disease Characteristics and Demographics⁵

Characteristic^a	BALVERSA (n=43)	BALVERSA + Cetrelimab (n=44)^b
Median age, years (range)	72 (45-92)	69 (51-91)
Male, n (%)	33 (76.7)	33 (75)
Race, n (%)
White	36 (83.7)	36 (81.8)
Asian	3 (7)	2 (4.5)
Not reported	4 (9.3)	6 (13.6)
Ethnicity, n (%)
Not Hispanic or Latino	39 (90.7)	37 (84.1)
Hispanic or Latino	1 (2.3)	2 (4.5)
Not reported	3 (7)	5 (11.4)
Geographic region
Europe	36 (83.7)	38 (86.4)
Rest of the world	5 (11.6)	3 (6.8)
North America	2 (4.7)	3 (6.8)
ECOG PS, n (%)
0	7 (16.3)	7 (15.9)
1	24 (55.8)	21 (47.7)
2	12 (27.9)	16 (36.4)
Presence of visceral metastases, n (%)
Lung	16 (37.2)	14 (31.8)
Bone	10 (23.3)	7 (15.9)
Liver	8 (18.6)	6 (13.6)
Primary tumor location, n (%)
Lower tract	31 (72.1)	38 (86.4)
Upper tract	12 (27.9)	6 (13.6)
PD-L1 status, n (%)
CPS ≥10 (high)	4 (9.3)	4 (9.1)
CPS <10 (low)	28 (65.1)	28 (63.6)
Not available	11 (25.6)	12 (27.3)
Any alterations, n (%)	42 (97.7)	44 (100)
FGFR gene alterations, n (%)
Mutations	36 (83.7)	31 (70.5)
FGFR3-S249C	20 (46.5)	21 (47.7)
FGFR3-R248C	7 (16.3)	2 (4.5)
FGFR3-Y373C	7 (16.3)	7 (15.9)
FGFR3-G370C	1 (2.3)	0
FGFR3-G370C/FGFR3-S249C	0	1 (2.3)
FGFR3-G370C/FGFR3-Y373C	1 (2.3)	0
Fusions	6 (14)	11 (25)
FGFR-TACC3_V1	5 (11.6)	7 (15.9)
FGFR3-TACC3	1 (2.3)	3 (6.8)
FGFR3-TACC3_V1/FGFR3-TACC3_V3	0	1 (2.3)
Mutations and fusions^c	0	2 (4.5)
Abbreviations: CPS, combined positive score; ECOG PS, Eastern Cooperative Oncology Group performance status; FGFR, fibroblast growth factor receptor; PD-L1, programmed cell death ligand-1. ^aNs for each parameter reflect nonmissing values.^bPercentages were calculated out of the number of patients with any FGFR alterations.^cMutations and fusions included each with FGFR3-S249/FGFR3-TACC3_V1 (n=1, 2.3%) and FGFR3-S249/FGFR3-TACC3_V3 (n=1, 2.3%) in the erdafitinib plus cetrelimab group.

Efficacy

In phase 1b response-evaluable patients (n=21), the confirmed overall response rate (ORR) was 52%. The confirmed ORR in 11 evaluable patients treated at the RP2D was 55%.²
- The disease control rate (DCR), which included unconfirmed complete responses (CRs) and partial responses (PRs), as well as stable disease (SD), was 91% overall and 100% at the RP2D.
Please see Table: Phase 1b: Summary of Best Overall Response for the Response-Evaluable Set.

Phase 1b: Summary of Best Overall Response for the Response-Evaluable Set²^,a

Patients With response, n (%)	DL1^a(n=4)	DL2A^b(n=3)	DL2B^c(n=3)	DL2^d(n=11)	Total (N=21)
ORR^e	2 (50)	2 (67)	1 (33)	6 (55)	11 (52)
DCR^f	4 (100)	2 (67)	2 (67)	11 (100)	19 (91)
Best overall response
PR (confirmed)	2 (50)	2 (67)	1 (33)	6 (55)	11 (52)
uPR	0	0	0	2 (18)	2 (10)
SD	2 (50)	0	1 (33)	3 (27)	6 (29)
PD	0	1 (33)	0	0	1 (5)
Not evaluable	0	0	1 (33)	0	1 (5)
Abbreviations: CR, complete response; DCR, disease control rate; DL, dose level; ORR, overall response rate; PD, progressive disease; PO₄, phosphate; PR, partial response; SD, stable disease; uPR, unconfirmed partial response. ^aIncludes all patients in the safety analysis set who have had a baseline and ≥1 adequate posttreatment disease evaluation, have had clinical signs or symptoms of disease progression, or died before the first posttreatment disease evaluation; 1 patient was not response-evaluable, as they did not have measurable disease at baseline; therefore, they were excluded from the analysis for response. ^aDL1=BALVERSA 6 mg plus cetrelimab 240 mg. ^bDL2A=BALVERSA 8 mg (no uptitration) plus cetrelimab 240 mg. ^cDL2B=BALVERSA 8 mg with uptitration to 9 mg based on serum PO₄ levels plus cetrelimab 240 mg (cetrelimab started at cycle 2 day 1). ^dDL2=BALVERSA 8 mg with uptitration to 9 mg based on serum PO₄ levels plus cetrelimab 240 mg. ^eIncludes only confirmed responses (CR + PR). ^fCR + PR + unconfirmed CR + unconfirmed PR + SD.

Final efficacy results are summarized in Table: Phase 2 Final Analysis: Efficacy Results.

Phase 2 Final Analysis: Efficacy Results^a,⁵

Response	BALVERSA (n=43)^b	BALVERSA + Cetrelimab (n=44)
ORR,^a % (95% CI)	44.2 (29.1-60.1)	54.5 (38.8-69.6)
Confirmed CR, n (%)	1 (2.3)	6 (13.6)
Confirmed PR, n (%)	18 (41.9)	18 (40.9)
Median DCR, %	88.4	79.5
Median DOR, months (95% CI)	9.7 (4.6-NE)	11.1 (8.8-NE)
Median time to response, months (range)	1.5 (1-6)	2.4 (1-14)
Ongoing treatment, n (%)	11 (25.6)	16 (36.4)
Median efficacy follow-up time, months (95% CI)	13.9 (8.3-21.9)	13.8 (11.1-19.7)
Median PFS, months (95% CI)	5.6 (4.3-7.4)	11 (5.5-13.6)
Median survival follow-up time, months (95% CI)	13.9 (12-19.6)	14.2 (11.1-18.5)
Median OS, months (95% CI)	16.2 (8.3-NE)	20.8 (12-NE)
12-month OS, % (95% CI)	56 (40-70)	68 (50-81)
Patients with FGFR mutations, n	36	31
ORR, % (95% CI)	50 (32.9-67.1)	51.6 (33.1-69.8)
Patients with FGFR fusion, n	6	11
ORR, % (95% CI)	16.7 (0.4-64.1)	54.5 (23.4-83.3)
Patients with evaluable PD-L1 and CPS <10, n	28	28
ORR, % (95% CI)	46.4 (27.5-66.1)	50 (30.6-69.4)
Abbreviations: CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; FGFR, fibroblast growth factor receptor; NE, not evaluable; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response. ^aClinical cutoff: December 19, 2022.^bOne patient in the BALVERSA arm was inevaluable.

In 4 patients treated with BALVERSA with PD-L1 high status (CPS ≥10), none responded (0/4), while 4 patients treated with BALVERSA plus cetrelimab, 75% (3/4) responded.

Safety

A total of 22 patients (dose level [DL]1, n=4; DL2A, n=3; DL2B, n=3; DL2, n=12) were evaluated in the phase 1b dose-escalation study, all of whom experienced AEs (see Table: Phase 1b: Overall Summary of Adverse Events).²
- 41% (n=9) experienced grade 3-4 treatment-related adverse events (TRAEs)
- 14% (n=3) experienced serious TRAEs
- 18% (n=4) experienced TRAEs leading to discontinuation of study drug
Dose-limiting toxicities (DLTs) were not observed at any DL; BALVERSA 8 mg with uptitration to 9 mg plus cetrelimab (DL2) was established as the RP2D.²
All patients reported AEs at the RP2D (n=12); 42% (n=5) experienced grade 3-4 TRAEs and 25% (n=3) experienced serious TRAEs (pneumonia and diarrhea [n=1], serous retinal detachment [n=1], and herpetic keratitis [n=1]).²
Overall, stomatitis was the most common treatment-emergent adverse event (TEAE), occurring in 73% of patients; grade 3 treatment-related stomatitis occurred in 14% of patients overall and 17% of patients at the RP2D.²
- A total of 2 patients died due to TEAEs: 1 patient due to large intestinal obstruction and 1 patient due to urinary tract infection (both were in the DL1 cohort).
Three patients had central serous retinopathy (CSR) events, a TEAE of special interest (grade 3 [n=1] and grade 2 [n=2]); all CSR events improved to grade 1 or resolved.²

Phase 1b: Overall Summary of Adverse Events²

Patients With Adverse Events, n (%)	DL1^a(n=4)	DL2A^b(n=3)	DL2B^c(n=3)	DL2^d(n=12)	Total (N=22)
Any TEAEs	4 (100)	3 (100)	2 (67)	11 (92)	20 (91)
Any TRAEs^e	4 (100)	3 (100)	2 (67)	11 (92)	20 (91)
Grade 3-4 TEAEs	3 (75)	2 (67)	1 (33)	5 (42)	11 (50)
Grade 3-4 TRAEs^e	1 (25)	2 (67)	1 (33)	5 (42)	9 (41)
Serious TEAEs	3 (75)	0	0	4 (33)	7 (32)
Serious TRAEs^e	0	0	0	3 (25)	3 (14)
TRAEs leading to discontinuation	0	1 (33)	0	3 (25)	4 (18)
Most common grade 3-4 TRAE, ie, stomatitis^f	1 (25)	0	0	2 (17)	3 (14)
TEAE of special interest, ie, CSR^f	0	1 (33)	0	2 (17)	3 (14)
Abbreviations: CSR, central serous retinopathy; DL, dose level; MedDRA, Medical Dictionary for Regulatory Activities; PO₄, phosphate; TEAE, treatment-emergent adverse event; TRAE, treatment-related adverse event. ^aDL1=BALVERSA 6 mg plus cetrelimab 240 mg. ^bDL2A=BALVERSA 8 mg (no uptitration) plus cetrelimab 240 mg. ^cDL2B=BALVERSA 8 mg with uptitration to 9 mg based on serum PO₄ levels plus cetrelimab 240 mg (cetrelimab started at cycle 2 day 1). ^dDL2=BALVERSA 8 mg with uptitration to 9 mg based on serum PO₄ levels plus cetrelimab 240 mg. ^eAn adverse event was categorized as related if assessed by the investigator as possibly, probably, or very likely related to the study drug. ^fAdverse events were coded using MedDRA v22.1.

The most common TEAEs and grade ≥3 TRAEs across all DLs in the phase 1b study are summarized in Tables: Phase 1b: Most Common TEAEs Occurring in >20% of Patients and Phase 1b: Grade ≥3 TRAEs, respectively.²

Phase 1b: Most Common TEAEs Occurring in >20% of Patients²

Adverse Event, n (%)	DL1^a(n=4)	DL2A^b(n=3)	DL2B^c(n=3)	DL2^d(n=12)	Total (N=22)
Stomatitis	3 (75)	3 (100)	1 (33)	9 (75)	16 (73)
Diarrhea	1 (25)	1 (33)	1 (33)	9 (75)	12 (55)
Dry mouth	2 (50)	2 (67)	1 (33)	7 (58)	12 (55)
Hyperphosphatemia	1 (25)	2 (67)	0	7 (58)	10 (46)
Dysgeusia	2 (50)	2 (67)	0	4 (33)	8 (36)
Dry skin	1 (25)	2 (67)	0	4 (33)	7 (32)
Alopecia	0	2 (67)	0	4 (33)	6 (27)
Asthenia	0	1 (33)	0	7 (58)	8 (36)
Decreased appetite	2 (50)	0	0	4 (33)	6 (27)
PPE	0	2 (67)	1 (33)	2 (17)	5 (23)
Pyrexia	2 (50)	0	0	3 (25)	5 (23)
Pruritus	1 (25)	1 (33)	0	3 (25)	5 (23)
Onycholysis	0	1 (33)	1 (33)	3 (25)	5 (23)
Abbreviations: DL, dose level; PO₄, phosphate; PPE, palmar-plantar erythrodysesthesia syndrome; TEAE, treatment-emergent adverse event. ^aDL1=BALVERSA 6 mg plus cetrelimab 240 mg. ^bDL2A=BALVERSA 8 mg (no uptitration) plus cetrelimab 240 mg. ^cDL2B=BALVERSA 8 mg with uptitration to 9 mg based on serum PO₄ levels plus cetrelimab 240 mg (cetrelimab started at cycle 2 day 1). ^dDL2=BALVERSA 8 mg with uptitration to 9 mg based on serum PO₄ levels plus cetrelimab 240 mg.

Phase 1b: Grade ≥3 TRAEs²^,a

Patients With TRAEs, n (%)	DL1^b(n=4)	DL2A^c(n=3)	DL2B^d(n=3)	DL2^e(n=12)	Total (N=22)
Stomatitis	1 (25)	0	0	2 (17)	3 (14)
Nail discoloration	0	0	1 (33)	0	1 (5)
Nail dystrophy	0	1 (33)	0	0	1 (5)
Onycholysis	0	1 (33)	0	0	1 (5)
Hypothyroidism	0	0	0	1 (8)	1 (5)
Serous retinal detachment	0	0	0	1 (8)	1 (5)
Autoimmune hepatitis	0	0	0	1 (8)	1 (5)
Pneumonia	0	0	0	1 (8)	1 (5)
GGT increased	0	0	0	1 (8)	1 (5)
Hyperphosphatemia	0	1 (33)	0	0	1 (5)
Abbreviations: DL, dose level; GGT, gamma-glutamyl transferase; PO₄, phosphate; TRAE, treatment-related adverse event. ^aNo grade 4 or 5 TRAEs were reported. ^bDL1=BALVERSA 6 mg plus cetrelimab 240 mg. ^cDL2A=BALVERSA 8 mg (no uptitration) plus cetrelimab 240 mg. ^dDL2B=BALVERSA 8 mg with uptitration to 9 mg based on serum PO₄ levels plus cetrelimab 240 mg (cetrelimab started at cycle 2 day 1). ^eDL2=BALVERSA 8 mg with uptitration to 9 mg based on serum PO₄ levels plus cetrelimab 240 mg.

The median durations of BALVERSA exposure were 5.6 months (range, 0.3-31.6) and 7.5 months (range, 0.5-23.1) in the BALVERSA and BALVERSA plus cetrelimab groups, respectively. The median duration of cetrelimab exposure was 7.8 months (range, 0-33).⁵
The overall safety summary is presented in Table: Phase 2: Overall Safety Summary.

Phase 2: Overall Safety Summary⁵

Patients With AEs, No. (%)	BALVERSA (n=43)	BALVERSA + Cetrelimab (n=44)
Any AEs	43 (100)	44 (100)
TRAEs^a	41 (95.3)	43 (97.7)
Grade 3-4 AEs	33 (76.7)	31 (70.5)
Related grade 3-4 AEs^a	20 (46.5)	20 (45.5)
Serious AEs	22 (51.2)	19 (43.2)
Treatment-related serious AEs^a	6 (14)	7 (15.9)
Grade 3-4 serious AEs	19 (44.2)	17 (38.6)
Treatment-related grade 3-4 serious AEs^a	5 (11.6)	5 (11.4)
Immune-related AEs	0	16 (36.4)
Treatment-related immune-related AEs^a	0	15 (34.1)
AEs leading to dose reduction^b	27 (62.8)	29 (65.9)
TRAEs leading to dose reduction^a,b	26 (60.5)	27 (61.4)
AEs leading to dose interruption^b	33 (76.7)	34 (77.3)
TRAEs leading to dose interruption^a,b	30 (69.8)	27 (61.4)
AEs leading to treatment discontinuation	10 (23.3)	18 (40.9)^c
TRAEs leading to treatment discontinuation^a	6 (14)	14 (31.8)^c
AEs leading to death^d	7 (16.3)	4 (9.1)
TRAEs leading to death^a,d	0	1 (2.3)
COVID-19-associated AEs	6 (14)	6 (13.6)
COVID-19-associated serious AEs	1 (2.3)	1 (2.3)
Abbreviations: AE, adverse event; COVID-19, coronavirus disease 2019; TRAE, treatment-related adverse event. ^aAn AE is categorized as related if assessed by the investigator as possibly, probably, or very likely related to either study drug. ^bDose reductions are applicable to only BALVERSA. Dose interruptions are applicable to either BALVERSA or cetrelimab. ^cTreatment discontinuations in the BALVERSA plus cetrelimab group include patients who discontinue either BALVERSA or cetrelimab or both. ^dAEs leading to death are based on an AE outcome of “Fatal.” In the BALVERSA group, these AEs were progressive disease (n=4 [general physical health deterioration, n=3; pain, n=1]), renal failure (n=1), COVID-19 pneumonia (n=1), and sepsis (n=1). In the BALVERSA plus cetrelimab group, these AEs were respiratory failure (n=2 [unrelated to study treatment, n=1; possibly related to cetrelimab, n=1]), progressive disease (n=1 [general physical health deterioration]), and pneumonia (n=1).

Common (occurring in ≥15% of patients) TRAEs are summarized in Table: Phase 2 Final Analysis: TRAEs Occurring in the Safety Population.

Phase 2 Final Analysis: TRAEs Occurring in the Safety Population⁵

Patients With TRAEs, n (%)	BALVERSA (n=43)		BALVERSA + Cetrelimab (n=44)
Patients With TRAEs, n (%)	Any Grade	Grade 3-4	Any Grade	Grade 3-4
Any TRAEs^a	41 (95.3)	20 (46.5)	43 (97.7)	19 (43.2)
Hyperphosphatemia	36 (83.7)	3 (7)	30 (68.2)	0
Stomatitis	30 (69.8)	7 (16.3)	25 (56.8)	4 (9.1)
Diarrhea	18 (41.9)	2 (4.7)	13 (29.5)	1 (2.3)
Dry mouth	16 (37.2)	0	25 (56.8)	1 (2.3)
Dry skin	14 (32.6)	0	16 (36.4)	0
Paronychia	10 (23.3)	2 (4.7)	4 (9.1)	0
Palmar-plantar erythrodysesthesia syndrome	9 (20.9)	1 (2.3)	10 (22.7)	3 (6.8)
Fatigue	8 (18.6)	1 (2.3)	7 (15.9)	0
ALT increased	7 (16.3)	0	8 (18.2)	2 (4.5)
Dysgeusia	7 (16.3)	1 (2.3)	9 (20.5)	0
Nail discoloration	7 (16.3)	0	3 (6.8)	0
Onycholysis	6 (14)	2 (4.7)	8 (18.2)	1 (2.3)
Decreased appetite	6 (14)	1 (2.3)	10 (22.7)	1 (2.3)
Nail dystrophy	5 (11.6)	0	8 (18.2)	1 (2.3)
Anemia	4 (9.3)	1 (2.3)	8 (18.2)	1 (2.3)
Lipase increased	2 (4.7)	1 (2.3)	7 (15.9)	2 (4.5)
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; MedDRA, Medical Dictionary for Regulatory Activities; TRAE, treatment-related adverse event. ^aPatients are counted only once for any given event, regardless of the number of times they experienced the event. The event experienced by the patient with the worst toxicity is used. If a patient has a missing toxicity for a specific AE, the patient is only counted in the total column for that AE. AEs are coded using MedDRA Version 24.1.^bOne treatment-related death occurred in the BALVERSA plus cetrelimab group (respiratory failure).^cListed are AEs of any cause by preferred term that were reported in more than 15% of the patients in either treatment group.

AEs of interest on the basis of the known BALVERSA safety profile included hyperphosphatemia, gastrointestinal disorders, nail disorders, skin disorders, eye disorders (excluding CSR), and CSR.⁶ See Table: Phase 2 Final Analysis: AEs of Special Interest Occurring in the Safety Population.

Phase 2 Final Analysis: AEs of Special Interest Occurring in the Safety Population⁶

Patients With TEAEs, n (%)	BALVERSA (n=43)		BALVERSA + Cetrelimab (n=44)
Patients With TEAEs, n (%)	Any Grade	Grade 3-4	Any Grade	Grade 3-4
Gastrointestinal disorders	36 (83.7)	3 (7)	37 (84.1)	5 (11.4)
Hyperphosphatemia	36 (83.7)	7 (16.3)	30 (68.2)	0
Nail disorders	27 (62.8)	5 (11.6)	26 (59.1)	2 (4.5)
Skin disorders	25 (58.1)	1 (2.3)	24 (54.5)	4 (9.1)
Eye disorders (excluding CSR)	16 (37.2)	2 (4.7)	18 (40.9)	1 (2.3)
CSR	9 (20.9)	1 (2.3)	9 (20.5)	0
Immune-related AEs	0	0	16 (36.4)	6 (13.7)
Hypothyroidism	0	0	3 (6.8)	0
Lipase increased	0	0	3 (6.8)	1 (2.3)
Dry mouth	0	0	2 (4.5)	0
ALT increased	0	0	2 (4.5)	2 (4.5)
AST increased	0	0	2 (4.5)	2 (4.5)
Anemia	0	0	2 (4.5)	0
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CSR, central serous retinopathy; TEAE, treatment-emergent adverse event.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, DERWENT Drug File (and/or other resources, including internal/external databases) was conducted on 16 March 2026.

References

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