BALVERSA®

(erdafitinib)

Medical inquiries

Connect with my medical science liaison

Chat live

Available Monday - Friday 9AM - 4:30PM ET

Call me now

Available Monday - Friday 9AM - 7:30PM ET

Email your inquiry

Call 1-800-526-7736

Available Monday - Friday 9AM - 8PM ET

Live video

Available Monday - Friday 9AM - 4:30PM ET

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

BALVERSA® (erdafitinib)

Medical Information

+ Save link

Use of BALVERSA in Cholangiocarcinoma

Last Updated: 10/29/2024

SUMMARY

RAGNAR (NCT04083976) is an ongoing, phase 2, open-label, single-arm, global, multicenter study evaluating the efficacy and safety of BALVERSA in adult and pediatric patients with unresectable, locally advanced, or metastatic solid tumor malignancies (tumor agnostic), fibroblast growth factor receptor (FGFR) mutations or fusions, and documented disease progression.¹ For complete study details, refer to https://clinicaltrials.gov/study/NCT04083976.
- Preliminary results of molecular eligibility screening for the RAGNAR study included 27% (30/110) of patients with cholangiocarcinoma (CCA). The predominant CCA FGFR alteration was FGFR2 fusion (80%), with FGFR2-BICC1 fusion as the most frequent variant.²
- Pant et al (2023)³ reported primary analysis results after a median follow-up of 17.9 months from a primary cohort of patients (N=217) with 16 different solid tumor types in the RAGNAR study. For 31 patients with CCA, the objective response rate (ORR) was 52%. In the overall population, BALVERSA-related grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 46% (100/217) of patients. The most common grade ≥3 TEAEs were stomatitis (12%), palmar-plantar erythrodysesthesia (6%), and hyperphosphatemia (5%). Safety was not evaluated separately for patients with CCA.
- Pant et al (2023)⁴ presented results after a median follow-up of 20.4 months from an expansion cohort of patients with CCA in the RAGNAR study (n=35). The independent review committee (IRC)-assessed ORR was 60% (21/35). The most common TEAEs were hyperphosphatemia (82.9%), diarrhea (80.0%), stomatitis (74.3%), and dry mouth (54.3%). Treatment-related TEAEs leading to dose reductions and dose interruptions were reported in the majority of patients (82.9% and 80.0%, respectively).
- Lugowska et al (2024)⁵ presented results from an exploratory cohort of patients with FGFR mutations that were not predefined as potentially susceptible alterations (n=53). Of the 53 patients, 10 (19%) had CCA. Efficacy and safety were not evaluated separately for patients with CCA.
LUC2001 (NCT02699606) was a phase 2a, open-label, multicenter, single-arm study that evaluated the efficacy and safety of BALVERSA in a molecularly defined subset of Asian patients with advanced CCA with disease progression after ≥1 prior systemic treatment.⁶^,⁷ For complete study details, refer to https://clinicaltrials.gov/study/NCT02699606.
- Park et al (2024)⁷ reported the results of the LUC2001 study. Patients with CCA met the primary endpoint of ORR (40.9%; 9/22; 95% CI, 20.7-63.6). Complete response and partial response were achieved in 4.5% (1/22) and 36.4% (8/22) of patients, respectively. Safety was not separately evaluated for patients with CCA. At least 1 TEAE was reported in all treated patients (n=35), and grade 3 TEAEs were reported in 62.9% (22/35) of patients. The most frequently reported TEAE was hyperphosphatemia (85.7%; 30/35).
- Preliminary results showed no apparent difference in the pharmacokinetics (PK) and PK/pharmacodynamic relationship among the Asian patients with CCA treated with BALVERSA compared with the global population.⁸
Gong et al (2024)⁹ reported the primary efficacy analysis results of the NCI-MATCH (EAY131; NCT02465060) Subprotocol K2 (EAY131-K2), a phase 2, open-label, single-arm study that evaluated the efficacy and safety of BALVERSA in patients with treatment-refractory solid tumors harboring FGFR1-4 mutations or FGFR1-3 fusions (N=35), including patients with CCA (n=9). Among the 25 efficacy evaluable patients, 2 patients achieved PR, whereas 1 patient reported stable disease (SD) as the best confirmed response to BALVERSA. Safety was not evaluated separately for patients with CCA.
Pant et al (2024)¹⁰ reported results from a pooled analysis of data from RAGNAR and LUC2001 evaluating the efficacy and safety of BALVERSA in patients with advanced or metastatic CCA and prespecified FGFR fusions or mutations. At a median follow-up of 14.7 months per IRC assessment, the ORR was 55.1% and the disease control rate (DCR) was 98.7%. Responses were reported in patients with FGFR 2/3 alterations and FGFR mutations and fusions. Objective response was similar in patients with and without FGFR co-alterations. Safety data were consistent with the known safety profile of BALVERSA.
A case series on the use of BALVERSA for the treatment of CCA has also been published.¹¹

CLINICAL DATA

Phase 2 Study - RAGNAR Expansion Cohort Analysis

Pant et al (2023)⁴ reported the efficacy and safety of BALVERSA in an expansion cohort of adult patients with CCA and prespecified FGFR alterations in the RAGNAR study (NCT04083976; n=35).

Study Design/Methods

Ongoing, phase 2, open-label, single-arm, global, multicenter study evaluating the efficacy and safety of BALVERSA in adult and pediatric patients (children aged ≥6 years) with unresectable, locally advanced, or metastatic solid tumor malignancies (tumor agnostic), FGFR mutations or fusions, and documented disease progression.³
The expansion cohort included adults aged ≥18 years who had advanced or metastatic CCA, predefined FGFR1-4 mutations/fusions (determined by bioinformatics and preclinical testing), documented disease progression, received ≥1 prior line of systemic therapy, and exhausted standard treatment options.
Patients received BALVERSA orally (PO) once daily on a 21-day cycle until disease progression or intolerable toxicity.³^,⁴
- Patients aged ≥15 years were initiated with BALVERSA 8 mg with possible pharmacodynamically-guided uptitration to 9 mg.³
Efficacy was assessed using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.³
Primary endpoint: IRC-assessed ORR.
Secondary endpoints: Investigator-assessed ORR, duration of response (DOR), DCR, clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety.

Results

Patient Characteristics

At the data cutoff, 35 patients with FGFR-altered CCA received BALVERSA, and median follow-up was 20.4 months.
The baseline characteristics are described in Table: RAGNAR CCA Expansion Cohort Analysis: Patient Demographics and Baseline Characteristics.

RAGNAR CCA Expansion Cohort Analysis: Patient Demographics and Baseline Characteristics⁴

Characteristic	CCA Expansion Cohort (n=35)
Age, median (range), years	57 (40-74)
Sex, n (%)
Female	23 (65.7)
Male	12 (34.3)
Time from progression/relapse during the last line of treatment to first dose, median (range), months^a	0.92 (0.2-9.6)
Baseline ECOG PS, n (%)
0	16 (45.7)
1	19 (54.3)
Presence of metastases: disease sites, n (%)	33 (94.3)
Lymph node	17 (48.6)
Liver	25 (71.4)
Lung	21 (60.0)
Other	11 (31.4)
Number of body sites with metastatic disease, n (%)^b
1	7 (21.2)
2	11 (33.3)
≥3	15 (45.5)
Visceral metastasis, n (%)^b	30 (90.9)
Prior line of therapy
1	13 (37.1)
≥2	22 (62.9)
Prior radiotherapy, n (%)	8 (22.9)
Prior cancer-related surgery/procedure, n (%)	18 (51.4)
Prior systemic therapy in advanced/metastatic setting, n (%)
Platinum-based therapy	34 (97.1)
Other^c	12 (34.3)
FGFR alteration type, n (%)
Mutation	3 (8.6)
Fusion	32 (91.4)
FGFR gene with alteration, n (%)
FGFR2	34 (97.1)
FGFR3	1 (2.9)
Abbreviations: CCA, cholangiocarcinoma; ECOG PS, Eastern Cooperative Oncology Group performance status; FGFR, fibroblast growth factor receptor. ^an=34; 1 patient had missing values. ^bn=33; applicable only to patients with metastatic disease. ^cExcludes gemcitabine, fluoropyrimidine, and immunotherapies.

Efficacy

Efficacy outcomes of the expansion cohort are summarized in Table: RAGNAR CCA Expansion Cohort Analysis: Key Efficacy Outcomes.
Median time to onset of response in the CCA expansion cohort was 1.5 months (range, 1.1-8.2).
Responses were observed in patients harboring FGFR mutations and fusions and in patients with co-occurring alterations.
The investigator-assessed efficacy endpoints were comparable to the IRC results.
Ten patients continued treatment for ≥4 weeks after radiographic disease progression (per investigator assessment).

RAGNAR CCA Expansion Cohort Analysis: Key Efficacy Outcomes⁴

Endpoint by IRC	CCA Expansion Cohort (n=35)
ORR, n (%) [95% CI]	21 (60.0) [42.1-76.1]
DCR, n (%) [95% CI]^a	35 (100.0) [90.0-100.0]
CBR, n (%) [95% CI]^b	25 (71.4) [53.7-85.4]
DOR, median (95% CI), months	5.55 (2.83-8.28)
PFS, median (95% CI), months	8.41 (5.49-9.72)
OS, median (95% CI), months	18.7 (8.9-NE)
Abbreviations: CBR, clinical benefit rate; CCA, cholangiocarcinoma; CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; IRC, independent review committee; NE, not evaluable; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; SD, stable disease. ^aDCR was defined as the proportion of patients with PR, CR, or SD. ^bCBR was defined as the proportion of patients with CR, PR, or durable SD (defined as a duration of ≥4 months).

Safety

Safety outcomes of the expansion cohort are summarized in Table: RAGNAR CCA Expansion Cohort Analysis: Safety.
The most common TEAEs in the CCA expansion cohort were hyperphosphatemia (82.9%), diarrhea (80.0%), stomatitis (74.3%), and dry mouth (54.3%).
Treatment-related TEAEs leading to dose reductions and dose interruptions were reported in the majority of patients in the expansion cohort (82.9% and 80.0%, respectively).

RAGNAR CCA Expansion Cohort Analysis: Safety⁴

Patients With ≥1 TEAE, n (%)	CCA Expansion Cohort (n=35)
Any treatment-related TEAEs	35 (100)
Grade ≥3 treatment-related TEAEs	25 (71.4)
Serious treatment-related TEAEs	9 (25.7)
Treatment-related TEAEs leading to treatment discontinuation	3 (8.6)
Treatment-related TEAEs leading to death	0
Abbreviations: CCA, cholangiocarcinoma; TEAE, treatment-emergent adverse event.

Phase 2 Study - LUC2001

Park et al (2024)⁷ reported the results of the LUC2001 study (NCT02699606; N=35).

Study Design/Methods

LUC2001 was a phase 2a, open-label, multicenter study that evaluated the efficacy and safety results of BALVERSA in a molecularly defined subset of Asian patients with advanced CCA with disease progression after ≥1 prior systemic treatment.⁶^,⁷
Patients received BALVERSA 8 mg orally once daily on a 28-day cycle, with uptitration to 9 mg.
- Uptitration to 9 mg once daily was performed if the serum phosphate level on day 14 of cycle 1 was less than the upper limit of normal (ULN) in the absence of drug-related toxicity.
Select inclusion criteria: Age ≥18 years, histologically or cytologically confirmed advanced CCA with ≥1 FGFR fusion/mutation, Eastern Cooperative Oncology Group performance status 0-1, and progressed after ≥1 line of treatment.
Select exclusion criteria: Receipt of chemotherapy, targeted therapies, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or ≥5 half-lives of the drug; receipt of prior selective FGFR inhibitor treatment; uncontrolled intercurrent illness; patients with persistent phosphate >ULN during screening; and nonrecovery from reversible toxicity of prior anti-cancer therapy.⁶^,⁷
Primary endpoint: Investigator-assessed ORR (CR+PR) per RECIST V1.1.
Secondary endpoints: PFS, DOR, DCR (CR + PR + SD), OS, safety and tolerability, and PK.

Results

Patient Characteristics

Of the 344 patients centrally screened for FGFR-activating mutations/rearrangements, 35 were enrolled. Twenty-two patients with CCA received BALVERSA 8 mg once daily.
Demographics and baseline characteristics of the enrolled patients with CCA are summarized in Table LUC2001: Demographics and Baseline Characteristics of Patients With CCA.

LUC2001: Demographics and Baseline Characteristics of Patients With CCA⁷

Characteristic	BALVERSA 8 mg (Once Daily) (n=22)
Age, median (range), years	51.5 (29-69)
Sex, n (%)
Male	13 (59.1)
Female	9 (40.9)
Genetic aberrations, n (%)
FGFR rearrangement	14 (63.6)
FGFR short variant	8 (36.4)
Histology, n (%)
Adenocarcinoma	20 (90.9)
Squamous cell carcinoma	0
Other	2 (9.1)
Cancer stage at study entry, n (%)
IV	22 (100.0)
Locations of metastatic disease at study entry, n (%)
Bone	1 (4.5)
Brain	0
Liver	8 (36.4)
Lung	8 (36.4)
Other	5 (22.7)
Prior systemic therapy, n (%)
Biological agents	1 (4.5)
Chemotherapy	22 (100.0)
Immunotherapy	0
ECOG PS, n (%)
0	12 (54.5)
1	10 (45.5)
Abbreviations: CCA, cholangiocarcinoma; ECOG PS, Eastern Cooperative Oncology Group performance status; FGFR, fibroblast growth factor receptor.

Efficacy

Median treatment duration for patients with CCA was 6.2 months (range, 1.5-35.6).
Median DOR was 7.3 months (range, 3.7-17.5).
Efficacy outcomes from the LUC 2001 study for patients with CCA are summarized in Table: LUC2001: Investigator-Assessed Efficacy Data for Patients With CCA.
The primary endpoint was met as the ORR lower boundary of the CI was >15%.

LUC2001: Investigator-Assessed Efficacy Data for Patients With CCA⁷

	FGFR Rearrangement	FGFR Short Variant	Total
Analysis set: treated patients^a (n)	14	8	22
ORR,^b n (%; 95% CI)^c	8 (57.1; 28.9-82.3)	1 (12.5; 0.3-52.7)	9 (40.9; 20.7-63.6)
DCR,^d n (%; 95% CI)^c	14 (100.0; 76.8-100.0)	4 (50.0; 15.7-84.3)	18 (81.8; 59.7-94.8)
Best overall response, n (%)
Complete response	1 (7.1)	0	1 (4.5)
Partial response	7 (50.0)	1 (12.5)	8 (36.4)
Stable disease	6 (42.9)	3 (37.5)	9 (40.9)
Progressive disease	0	4 (50.0)	4 (18.2)
Not evaluable	0	0	0
PFS^e
Median (95% CI), months	12.5 (3.7-16.6)	2.7 (1.7-5.5)	5.6 (3.6-12.7)
6-month PFS rate (95% CI), %	71 (41-88)	0 (NE-NE)	45 (24-64)
12-month PFS rate (95% CI), %	57 (28-78)	0 (NE-NE)	36 (17-56)
OS^e
Median (95% CI), months	40.2 (12.4-NE)	13.8 (4.9-NE)	25.8 (9.9-NE)
6-month OS rate (95% CI), %	100 (100-100)	60 (13-88)	89 (62-97)
12-month OS rate (95% CI), %	85 (51-96)	60 (13-88)	77 (50-91)
Abbreviations: CCA, cholangiocarcinoma; CI, confidence interval; DCR, disease control rate; FGFR, fibroblast growth factor receptor; NE, not estimable; ORR, objective response rate; OS, overall survival; PFS, progression-free survival. Note: Complete response and partial response must be confirmed by repeat assessments ≥4 weeks from the initial observation. For a response to qualify as stable disease, follow-up measurements must have met the stable disease criteria at least once at a minimum interval not less than 6 weeks after the first dose of study agent. ^aAll patients with CCA received BALVERSA 8 mg once daily. ^bORR is defined as patients with complete response or partial response to treatment. ^c95% CI is based on the Clopper-Pearson method. ^dDCR is defined as patients with complete response, partial response, and stable disease after treatment. ^eBased on Kaplan-Meier estimate.

Safety

Safety data for patients with CCA were not reported separately.
The safety profile was consistent with the known safety profile of BALVERSA.
At least 1 TEAE was reported in all patients (N=35), and grade ≥3 TEAEs were reported in 62.9% (22/35) of patients.
Serious AEs occurred in 45.7% (16/35) of patients, with 8.6% (3/35) of these being drug-related.
The most frequently reported TEAE was hyperphosphatemia (85.7%; 30/35).
Other common TEAEs included dry mouth, stomatitis, increased alanine aminotransferase, increased aspartate aminotransferase, diarrhea, decreased appetite, dry skin, and constipation.
TEAEs leading to dose reduction occurred in 54.3% (19/35) of patients due to nail disorder, hyperphosphatemia, and stomatitis.
TEAEs leading to discontinuation occurred in 5.7% (2/35) of patients due to arthralgia and rash erythematous and were considered related to treatment.
One patient died due to sepsis, which was not considered related to the treatment.

Phase 2 Study - NCI-MATCH Subprotocol K2 Study

Gong et al (2024)⁹ reported the primary efficacy analysis results of the NCI-MATCH (EAY131; NCT02465060) Subprotocol K2 study (EAY131-K2; N=35 including patients with CCA [n=9]).

Study Design/Methods

This phase 2, open-label, single-arm study evaluated the efficacy and safety of BALVERSA PO once daily in adult patients with treatment-refractory solid tumors harboring FGFR1-4 mutations or FGFR1-3 fusions.
Eligible patients had any solid tumor except transitional cell carcinoma of the bladder and/or urothelial tract, lymphoma, or myeloma (progressing on standard treatment or for whom no standard treatment was available); predefined FGFR1-4 mutations or FGFR1-3 fusions, as determined by tumor profiling; and were FGFR inhibitor treatment-naïve.
- Patients were initiated with BALVERSA 8 mg with possible uptitration to 9 mg based on cycle 1 day 15 serum phosphate levels and in the absence of significant toxicity.
Efficacy was assessed using RECIST version 1.1 every 2 cycles (for the first 26 cycles) and then every 3 cycles thereafter (until disease progression).
- Primary endpoint: ORR.
- Key secondary endpoints: PFS, OS, and safety.

Results

Efficacy

Of the 35 enrolled patients, 25 were considered evaluable for the primary efficacy analysis, including patients with CCA (n=9).
- At the cutoff date of June 02, 2022, the ORR was 16% (4/25; 90% CI, 5.7-33.0).
- Overall, 28% (7/25) of patients each had SD and progressive disease as the best confirmed response; 7 patients were unevaluable for response.
- The median OS was 11 months and the median PFS was 3.6 months.
Among patients with a PR or PFS >168 days (including the patients with tumor FGFR alterations not centrally confirmed and therefore not included in the primary analysis [n=33]), 4 patients had CCA.
- Two patients with CCA (FGFR2 fusion) had PR as best response and PFS of 11.5 and 18 months, respectively.
- Another patient with CCA (FGFR2 fusion) had SD as the best response and PFS of 8.4 months.
- One patient with CCA and unconfirmed FGFR status had SD as the best response and PFS of 7.1 months.

Safety

Safety was not evaluated separately for patients with CCA.
Of the 35 patients who received BALVERSA, 34 were assessed for safety.
- The most common grade 1-2 treatment-related adverse events (TRAEs) were dry mouth (18/34; 52.9%), diarrhea (17/34; 50.0%), fatigue (16/34; 47.1%), and anemia (11/34; 32.4%).
- The most frequent grade 3 TRAEs were mucositis (5/34; 14.7%), followed by fatigue, anemia, nausea, paronychia, and palmar-plantar erythrodysesthesia syndrome (1/34; 2.9% each).
- No grade 4-5 TRAEs were reported.
AEs leading to discontinuation were reported in 16% (4/25) of patients. One discontinuation due to death was attributed to grade 5 disease progression deemed unrelated to BALVERSA treatment.
Dose reductions were reported at 14 instances across 97 treatment cycles (14%).

Pooled Analysis of RAGNAR and LUC2001

Pant et al (2024)¹⁰ reported results from a pooled analysis of data from RAGNAR (n=66) and LUC2001 (n=12) evaluating the efficacy and safety of BALVERSA in patients with advanced or metastatic CCA and prespecified FGFR fusions or mutations.

Study Design/Methods

Efficacy outcomes: IRC-assessed ORR (CR + PR) per RECIST version 1.1, DOR, DCR (CR + PR + SD), PFS, and OS.
Safety outcomes: TEAEs.

Results

Patient Characteristics

At the data cutoff (RAGNAR: December 4, 2023; LUC2001: November 19, 2021), 78 patients received BALVERSA with a median follow-up of 14.7 months.
The baseline characteristics are described in Table: Pooled Analysis of RAGNAR and LUC2001: Patient Demographics and Baseline Characteristics.
FGFR co-alterations were assessed in the broad panel cohort of the RAGNAR study (n=31).
- The most frequently co-altered genes included BAP1 (19%), CDKN2A (13%), CDKN2B (13%), PIK3CA (10%), MTAP (6%), and TP53 (3%).

Pooled Analysis of RAGNAR and LUC2001: Patient Demographics and Baseline Characteristics¹⁰

Characteristic	N=78
Age, median (range), years	56.0 (24-77)
Sex, female, n (%)	47 (60.3)
Race, n (%)
White	37 (47.4)
Asian	30 (38.5)
Black or African American	2 (2.6)
Native Hawaiian or other Pacific Islander	1 (1.3)
Not reported	8 (10.3)
ECOG PS, n (%)
0	34 (43.6)
1	44 (56.4)
Visceral metastases, n (%)^a	69 (92.0)
Time from progression/relapse on the last line of treatment to 1st dose, median (range), months^b	0.95 (0.1-67.1)
Number of prior lines of anticancer therapies
Median (range)	2.0 (1.0-6.0)
1, n (%)	31 (39.7)
2, n (%)	33 (42.3)
≥3, n (%)	14 (17.9)
Prior systemic therapy in advanced/metastatic setting, n (%)
Chemotherapy	78 (100.0)
Immunotherapy	11 (14.1)
Other systemic therapy	69 (88.5)
Best response to last line of prior systemic therapy
ORR, n (%) [95% CI]	13 (16.7) [9.2-26.8]
FGFR alterations, n (%)
FGFR2	73 (93.6)
FGFR3	5 (6.4)
FGFR alteration type, n (%)
FGFR fusion	71 (91.0)
FGFR mutation	7 (9.0)
Abbreviations: CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; FGFR, fibroblast growth factor receptor; ORR, objective response rate.^an=75, applicable only to patients with metastatic disease. ^bn=75, applicable only to patients with non-missing values for progression/relapse date of last line of treatment.

Efficacy

Key efficacy outcomes are summarized in Table: Pooled Analysis of RAGNAR and LUC2001: Key Efficacy Outcomes.

Pooled Analysis of RAGNAR and LUC2001: Key Efficacy Outcomes¹⁰

Outcome	Per IRC Assessment	Per Investigator Assessment
CR, n	1	3
PR, n	42	31
SD, n	34	39
ORR, %, (95% CI)^a	55.1 (43.4-66.4)	43.6 (32.4-55.3)
DCR, %, (95% CI)^b	98.7 (93.1-100)	93.6 (85.7-97.9)
CBR, %, (95% CI)^c	70.5 (59.1-80.3)	-
Time to response, median (range), months	1.7 (1.4-2.8)	-
DOR, median (95% CI), months^d	6.9 (4.37-8.61)	-
PFS, median (95% CI), months^d	8.5 (6.83-9.72)	-
OS, median (95% CI), months^d	18.1 (13.40-24.28)	-
Abbreviations: CBR, clinical benefit rate; CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; IRC, independent review committee; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease. ^aORR was defined as the proportion of patients with CR + PR per the RECIST version 1.1 criteria by IRC. ^bDCR was defined as the proportion of patients with CR + PR + SD per the RECIST version 1.1 criteria by IRC. ^cCBR was defined as the proportion of patients with CR, PR, or durable SD defined as a duration of ≥4 months. ^dN=78.

Responses were observed in patients with altered FGFR2 and FGFR3 and across FGFR mutations and fusions (See Table: Pooled Analysis of RAGNAR and LUC2001: Key Efficacy Outcomes by FGFR Alterations).
- Objective response to BALVERSA in patients with FGFR co-alterations was similar to that in patients without co-alterations.

Pooled Analysis of RAGNAR and LUC2001: Key Efficacy Outcomes by FGFR Alterations¹⁰

Outcome	FGFR2 Alteration (n=73)	FGFR3 Alteration (n=5)	FGFR Mutation (n=7)	FGFR Fusion (n=71)
ORR, n (%), [95% CI]	41 (56.2) [44.1-67.8]	2 (40.0) [5.3-85.3]	2 (28.6) [3.7-71.0]	41 (57.7) [45.4-69.4]
DOR, median (95% CI), months	6.93 (4.37-8.28)	NE (2.83-NE)	NE (2.76-NE)	6.93 (4.37-8.28)
Abbreviations: CI, confidence interval; DOR, duration of response; FGFR, fibroblast growth factor receptor; NE, not evaluable; ORR, objective response rate.

Safety

The most common BALVERSA-related TEAEs are summarized in Table: Pooled Analysis of RAGNAR and LUC2001: Summary of BALVERSA-Related TEAEs.

Pooled Analysis of RAGNAR and LUC2001: Summary of BALVERSA-Related TEAEs¹⁰

TEAEs, n (%)	N=78
Any TEAEs	78 (100)
Grade ≥3 TEAEs	50 (64.1)
Serious TEAEs	12 (15.4)
TEAEs leading to dose reduction	65 (83.3)
TEAEs leading to dose interruption	64 (82.1)
TEAEs leading to treatment discontinuation	6 (7.7)
TEAEs leading to death	0
TEAE by Preferred Term in ≥20% of Patients, n (%)	Any Grade	Grade ≥3
Hyperphosphatemia	64 (82.1)	4 (5.1)
Stomatitis	54 (69.2)	14 (17.9)
Palmar-plantar erythrodysesthesia	40 (51.3)	5 (6.4)
Diarrhea	39 (50.0)	2 (2.6)
Dry mouth	38 (48.7)	2 (2.6)
Alopecia	25 (32.1)	0
Dry skin	25 (32.1)	2 (2.6)
Onycholysis	21 (26.9)	7 (9.0)
Dry eye	19 (24.4)	1 (1.3)
Nail discoloration	18 (23.1)	1 (1.3)
Epistaxis	18 (23.1)	0
Paronychia	17 (21.8)	4 (5.1)
Increased AST	17 (21.8)	0
Dysgeusia	17 (21.8)	0
Increased ALT	16 (20.5)	3 (3.8)
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; MedDRA, Medical Dictionary for Regulatory Activities; TEAE, treatment-emergent adverse event. Note: Adverse events are coded using MedDRA version 24.1. Patients were counted only once for any given event, regardless of the number of times they actually experienced the event.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and DerwentDrug File (and/or other resources, including internal/external databases) was conducted on 29 August 2024.

References

Show

1	Janssen Research & Development LLC. A study of erdafitinib in participants with advanced solid tumors and fibroblast growth factor receptor (FGFR) gene alterations (RAGNAR). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2024 August 29]. Available from: https://clinicaltrials.gov/study/NCT04083976 NLM Identifier: NCT04083976.
2	Massard C, Pant S, Iyer G, et al. Preliminary results of molecular screening for FGFR alterations in the RAGNAR histology-agnostic study with the FGFR inhibitor (FGFRi) erdafitinib. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 4-8, 2021; Virtual.
3	Pant S, Schuler M, Iyer G, et al. Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): an international, single-arm, phase 2 study. Lancet Oncol. 2023;24(8):925-935.
4	Pant S, Schuler MH, Iyer G, et al. Efficacy and safety of erdafitinib in adults with cholangiocarcinoma (CCA) with prespecified fibroblast growth factor receptor alterations (FGFRalt) in the phase 2 open-label, single-arm RAGNAR trial: expansion cohort results. Poster presented at: American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium; January 19-21, 2023; San Francisco, California, and Virtual.
5	Lugowska I, Schuler M, Loriot Y, et al. Efficacy of erdafitinib in adults with advanced solid tumors and non-prespecified fibroblast growth factor receptor mutations in the phase 2 RAGNAR trial: exploratory cohort. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2024; Chicago, IL.
6	Janssen Research & Development, LLC. A study to evaluate the clinical efficacy of JNJ-42756493 (erdafitinib), a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in Asian participants with advanced non-small-cell lung cancer, urothelial cancer, esophageal cancer or cholangiocarcinoma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2024 August 29]. Available from: https://clinicaltrials.gov/study/NCT02699606 NLM Identifier: NCT02699606.
7	Park JO, Feng YH, Su WC, et al. Erdafitinib in Asian patients with advanced solid tumors: an open-label, single-arm, phase IIa trial. BMC Cancer. 2024;24(1):1006.
8	Chen YY, Park JO, Su WC, et al. Preliminary results of a phase 2a study to evaluate the clinical efficacy and safety of erdafitinib in Asian patients with biomarker-selected advance cholangiocarcinoma (CCA). Poster presented at: European Society for Medical Oncology (ESMO) Congress; October 19-23, 2018; Munich, Germany.
9	Gong J, Mita AC, Wei Z, et al. Phase II study of erdafitinib in patients with tumors with fibroblast growth factor receptor mutations or fusions: results from the NCI-MATCH ECOG-ACRIN trial (EAY131) subprotocol K2. JCO Precis Oncol. 2024;8(8):e2300407.
10	Pant S, Park JO, Su WC, et al. Efficacy and safety of erdafitinib in patients with advanced or metastatic cholangiocarcinoma and FGFR alterations: pooled analysis of RAGNAR and LUC2001 studies. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2024; Chicago, IL.
11	Brito GA, Pereira BJ, Baptista AL, et al. FGFR inhibitors in cholangiocarcinoma and urothelial bladder cancer resulting in hyperphosphatemia, low parathormone, and high calcitriol: the side effects of FGF23 blockade [abstract]. J Am Soc Nephrol. 2023;34:478. Abstract FR-PO268.