PublishedOctober 15, 2026
JournalClinical Cancer Research
TrialBLC3001 (THOR, randomized phase 3), NCT03390504

Erdafitinib Improves Overall Survival Over Chemotherapy but Not Over Pembrolizumab in FGFR3-Altered Urothelial Cancer: FDA Approval Summary of the Phase 3 THOR Trial

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Article Summary
  • This FDA approval summary describes the randomized, open-label phase 3 THOR trial (BLC3001) behind the January 19, 2024 traditional approval of erdafitinib for locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 alterations after prior PD-(L)1 therapy. In Cohort 1 (266 patients), median overall survival was 12.1 months (95% CI: 10.3, 16.4) with erdafitinib versus 7.8 months (95% CI: 6.5, 11.1) with chemotherapy (HR 0.64; 95% CI: 0.47, 0.88; p=0.0050).
  • Median progression-free survival was 5.6 months versus 2.7 months (HR 0.58; 95% CI: 0.44, 0.78; p=0.0002), and confirmed objective response rate was 35.3% (95% CI: 27.3, 43.9) versus 8.5% (95% CI: 4.3, 14.6). Dose reductions and interruptions were common.
  • In Cohort 2 (351 patients, erdafitinib versus pembrolizumab), the overall survival HR was 1.18 (95% CI: 0.92, 1.51; p=0.18), and the primary endpoint was not met. The label therefore does not recommend erdafitinib for patients who are eligible for and have not received prior PD-(L)1 inhibitor therapy. The source is an FDA regulatory summary, not an independent trial report.

Why This Study Matters

Options for second- and later-line treatment of locally advanced or metastatic urothelial carcinoma (la/mUC) are limited. Many patients will already have received an immune checkpoint inhibitor before second-line treatment. Approximately 20% of all la/mUC tumors have FGFR alterations, and about 80% of the FGFR alterations in la/mUC are FGFR3 point mutations.

Erdafitinib is an oral kinase inhibitor of FGFR1 through FGFR4. It received accelerated approval in 2019 based on 87 patients in the single-arm BLC2001 study (ORR 32.2%; 95% CI: 22.4, 42.0). This summary covers the randomized evidence that supported traditional approval.

1
Overall survival improved versus chemotherapy (Cohort 1). Median OS was 12.1 months (95% CI: 10.3, 16.4) with erdafitinib versus 7.8 months (95% CI: 6.5, 11.1) with chemotherapy; HR 0.64 (95% CI: 0.47, 0.88); p=0.0050.
2
Progression-free survival. Median PFS was 5.6 months versus 2.7 months; HR 0.58 (95% CI: 0.44, 0.78); p=0.0002.
3
Response. Confirmed objective response rate (ORR) was 35.3% (95% CI: 27.3, 43.9) versus 8.5% (95% CI: 4.3, 14.6).
4
No survival advantage over pembrolizumab (Cohort 2). OS HR was 1.18 (95% CI: 0.92, 1.51; p=0.18), leading to a limitation of use.

Study Design

BLC3001 was a randomized, open-label, multicenter, global, phase 3 trial with 2 independent cohorts. Patients were assigned to a cohort by whether they had received prior anti-PD-(L)1 treatment. Cohort 1 supported the traditional approval; Cohort 2 informed the limitation of use. The number of sites is not specified in the source.

Cohort 1 at a glance

266 patients (erdafitinib n=136; chemotherapy n=130); 1:1 randomization stratified by region, ECOG status (0 or 1 vs 2) and visceral or bone metastases; erdafitinib 8 mg once daily, up-titrated to 9 mg at 14 to 21 days if no ocular disorders or Grade ≥2 adverse reactions and serum phosphate <9 mg/dL; control docetaxel 75 mg/m² or vinflunine 320 mg/m² every 3 weeks.

The primary endpoint was OS in both cohorts. Cohort 1 was designed so that 208 events would provide 85% power to detect an OS hazard ratio of 0.65 (2-sided test, 0.05 significance level, one interim analysis). PFS and ORR (investigator-assessed per RECIST 1.1) were tested in a gated hierarchy.

Patient Population

Eligible patients had la/mUC with selected FGFR3 or FGFR2 alterations and disease progression after 1 or 2 prior treatments, at least one of which included a PD-(L)1 inhibitor. No patients in Cohort 1 had FGFR2 alterations. FGFR alterations were identified by the QIAGEN therascreen FGFR RGQ RT-PCR kit in 75% of patients and by local next-generation sequencing in 25%.

CharacteristicErdafitinib (N=136)Chemotherapy (N=130)
Median age, years (range)66 (32, 85)68 (35, 86)
Male, n (%)96 (71)94 (72)
ECOG 0 / 1 / 2, n (%)63 (46) / 61 (45) / 12 (9)51 (39) / 66 (51) / 13 (10)
FGFR3 single point mutation, n (%)105 (77)102 (78)
FGFR3 single fusion, n (%)24 (18)18 (14)
Visceral metastases, n (%)101 (74)97 (75)
Upper tract primary, n (%)41 (30)48 (37)
Two prior systemic therapy lines, n (%)90 (66)97 (75)

Primary Endpoint Results

At the prespecified interim analysis, planned at 65% but occurring at an observed 75% of planned OS events, erdafitinib showed statistically significant improvements in OS, PFS and ORR compared with chemotherapy.

EndpointErdafitinibChemotherapyHR (95% CI); p
Median OS, months (95% CI)12.1 (10.3, 16.4)7.8 (6.5, 11.1)0.64 (0.47, 0.88); p=0.0050
OS events, n (%)77 (56.6%)78 (60.0%)
Median PFS, months (95% CI)5.6 (4.4, 5.7)2.7 (1.8, 3.7)0.58 (0.44, 0.78); p=0.0002
Confirmed ORR (95% CI)35.3% (27.3, 43.9)8.5% (4.3, 14.6)p<0.001
Complete response5.1%0.8%
Partial response30.1%7.7%

Hazard ratios are from an unstratified Cox model; p-values are 2-sided and compared with 0.019 of the allocated alpha for the interim analysis.

Cohort 2. For the 351 randomized patients, the OS HR for erdafitinib versus pembrolizumab was 1.18 (95% CI: 0.92, 1.51; p=0.18), with median OS of 10.9 months (95% CI: 9.2, 12.6) versus 11.1 months (95% CI: 9.7, 13.6). Cohort 2 did not meet its primary endpoint of OS superiority.

Subgroup Analyses

The source reports subgroup results qualitatively. Results appeared to favor erdafitinib across relevant exploratory subgroup analyses, including FGFR3 mutations versus fusions, prior PD-(L)1 inhibitor in the neoadjuvant/adjuvant versus metastatic setting, prior platinum therapy or not, and receipt of docetaxel versus vinflunine in the control arm.

Subgroup (exploratory)Direction in sourceHR / CI / p-value
FGFR3 mutations vs fusionsAppeared to favor erdafitinibNot specified in source
Prior PD-(L)1 inhibitor: neoadjuvant/adjuvant vs metastaticAppeared to favor erdafitinibNot specified in source
Prior platinum therapy or notAppeared to favor erdafitinibNot specified in source
Docetaxel vs vinflunine controlAppeared to favor erdafitinibNot specified in source

Safety Profile

Ocular disorders (including central serous retinopathy/retinal pigment epithelial detachment and dry eye) and hyperphosphatemia are Warnings and Precautions in the label. Dose interruptions and reductions for toxicity were common: treatment interruption for an adverse reaction was required in 72% and dose reduction in 69% of patients who received erdafitinib, and 14% discontinued because of adverse reactions, most commonly for nail and eye disorders. Dose up-titration occurred in 77% in BLC3001 Cohort 1 versus 41% in BLC2001.

Adverse reaction requiring dose reduction (>4%)Erdafitinib-treated patients
Nail disorders27%
Stomatitis19%
Eye disorders17%
Palmar-plantar erythrodysesthesia syndrome12%
Diarrhea7%
Dry mouth4.4%
Hyperphosphatemia4.4%

Arm-by-arm adverse event rates are in the source’s Supplementary Table S2 and are not reproduced here (not specified in the main text).

Interpretation and Broader Context

Because Cohort 2 showed a trend towards OS detriment (HR 1.18), the label states erdafitinib is not recommended for patients who are eligible for and have not received prior PD-(L)1 inhibitor therapy. The authors suggest the Cohort 2 result may reflect longer response durations with immunotherapy (median 14.4 months for pembrolizumab versus 6.9 months for erdafitinib) rather than lower erdafitinib activity.

Despite the frequent need for dose reductions of erdafitinib due to adverse reactions, the FDA considered the overall benefit-risk profile favorable for the indicated population.
— Maguire et al., Clin Cancer Res 2026 (Conclusion). Note: the source is an FDA regulatory summary, not an independent trial report.

Limitations

THOR was open-label. The agency flagged asymmetric dropout among randomized-not-treated patients (13.8% on chemotherapy versus <1% on erdafitinib), and judged that sensitivity analyses, similar baseline characteristics, similar PFS censoring (26% versus 31%) and a survival sweep recovering data for 9 of 19 such patients supported the primary analysis. The OS result in Cohort 1 came from a prespecified interim analysis, and the subgroup analyses were exploratory, with hazard ratios and p-values not given in the source. Cohort 2 did not show a survival advantage over pembrolizumab. The source is an FDA approval summary and not an independent trial report; the sponsor (the Applicant) is Janssen Biotech, Inc, and the number of sites is not specified in the source.

Trial registration

Primary source: DOI 10.1158/1078-0432.CCR-26-1154 · PubMed 42584173 · PMC13575886

References

  1. Maguire WF, Chang E, Mulkey F, et al. FDA Approval Summary: Erdafitinib for FGFR3-Altered Locally Advanced or Metastatic Urothelial Carcinoma. Clin Cancer Res. 2026. DOI: 10.1158/1078-0432.CCR-26-1154. PMID: 42584173. PMCID: PMC13575886. ClinicalTrials.gov: NCT03390504.