Balversa (erdafitinib) / J&J, Otsuka - LARVOL DELTA

THOR: A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations (clinicaltrials.gov) - P3 | N=629 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2026 ➔ Dec 2027

Trial completion date • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Phase I study of LY3866288, a potent, highly isoform-selective FGFR3 inhibitor in FGFR3-altered advanced solid tumors (FORAGER-1): Dose optimization (ESMO 2025) - P1 | "Preclinically, LY increases nectin 4 cell surface expression and enhances the antitumor activity of enfortumab vedotin (EV) in FGFR3 -altered mUC in vivo models...LY plus EV and pembrolizumab (EVP) is being studied in 1L mUC (B5)...TEAEs associated with poor tolerance and compliance to erdafitinib were uncommon (PPE 7%, onycholysis 0%, retinopathy 0%)...Cohort B5 opened at 200 mg BID and updated data will be presented. Conclusions LY3866288 at 200 mg BID was well-tolerated and demonstrated promising antitumor activity in FGFRi pretreated and naive pts with FGFR3 -altered mUC, warranting further study as monotherapy and combined with EVP."

Metastases • P1 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3 • NECTIN4

Phase 2 study of the efficacy and safety of erdafitinib in patients (pts) with intermediate-risk non–muscle-invasive bladder cancer (IR-NMIBC) with FGFR3/2 alterations (alt) in THOR-2: Cohort 3 interim analysis. (ASCO-GU 2023) - P2 | "Data from Cohort 3 of THOR-2 demonstrate efficacy in adult pts with IR-NMIBC with FGFRalt. Safety data were consistent with the known safety profile of erda. Clinical trial information: NCT04172675."

Clinical • P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

FGFR inhibitors in urothelial cancer: Contextualizing THOR within the new treatment landscape. (PubMed, Med) - "The phase 3 THOR trial compared the efficacy of erdafitinib to chemotherapy or immunotherapy in FGFR3/2-altered advanced UC. THOR offers valuable data informing sequencing strategies, reinforcing the need for molecular testing in UC."

Journal • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

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. (PubMed, JCO Precis Oncol) - "This study met its primary end point in patients with several pretreated solid tumor types harboring FGFR1-3 mutations or fusions. These findings support advancement of erdafitinib for patients with fibroblast growth factor receptor-altered tumors outside of currently approved indications in a potentially tumor-agnostic manner."

Journal • P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • Urothelial Cancer • FGFR • IDH1

Erdafitinib in Patients with FGFR-altered Advanced or Metastatic Cholangiocarcinoma. (PubMed, Clin Cancer Res) - "Pooled analyses confirm the robust efficacy of erdafitinib in a diverse population of pretreated patients with advanced/metastatic CCA harboring prespecified FGFR alterations. These findings are consistent with previously observed efficacy of FGFR-targeted agents in patients with CCA."

Journal • Biliary Cancer • Cholangiocarcinoma • Dental Disorders • Dermatology • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Solid Tumor • Stomatitis • Urothelial Cancer • Xerostomia • FGFR • FGFR3

THOR-2 cohort 1: Results of erdafitinib (ERDA) vs intravesical chemotherapy (chemo) in patients (pts) with high-risk non–muscle-invasive bladder cancer (HR NMIBC) with select fibroblast growth factor receptor alterations (FGFRALT) who received prior bacillus calmette-guérin (BCG) treatment (ESMO 2023) - P2 | "Methods Adult pts with recurrent, BCG-treated, papillary-only HR NMIBC (high-grade Ta/T1) and select FGFRalt refusing/ineligible for RC were randomized 2:1 to 6 mg oral erda or investigator's choice of intravesical chemo (mitomycin C or gemcitabine). Conclusions Erda prolonged RFS compared with chemo in pts with papillary-only HR NMIBC with FGFRalt who had recurrence after BCG tx. Erda toxicity was generally consistent with the known safety profile of oral FGFR inhibitors."

Clinical • Late-breaking abstract • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR

Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): an international, single-arm, phase 2 study. (PubMed, Lancet Oncol) - P2 | "RAGNAR results show clinical benefit for erdafitinib in the tumour-agnostic setting in patients with advanced solid tumours with susceptible FGFR alterations who have exhausted other treatment options. These results support the continued development of FGFR inhibitors in patients with advanced solid tumours."

Journal • Metastases • P2 data • Dental Disorders • Genito-urinary Cancer • Oncology • Renal Disease • Solid Tumor • Stomatitis • Urothelial Cancer • FGFR • FGFR1

Erdafitinib (erda) vs chemotherapy (chemo) in patients (pts) with advanced or metastatic urothelial cancer (mUC) with select FGFR alterations (FGFRalt): Subgroups from the phase III THOR study (ESMO 2023) - P3 | "Methods Pts (≥18 y) with unresectable advanced/mUC and select FGFR3/2alt (mutations/fusions), ECOG PS 0-2, adequate organ function, progression on/after 1-2 prior lines of systemic tx that included anti-PD-(L)1 were randomized 1:1 to erda (8 mg with pharmacodynamically guided uptitration to 9 mg) QD or investigator's choice of chemo (docetaxel or vinflunine) Q3W until disease progression or intolerable toxicity. No new safety signals were observed. These results support the role of erda to treat pts with FGFRalt mUC after anti-PD-(L)1 tx."

Clinical • IO biomarker • Metastases • P3 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR • FGFR3 • PD-L1

Durable and deep partial response in FGFR3::TACC3 glioblastoma with FGFR inhibitor Erdafitinib and Tumor Treating Fields (EANO 2026) - "Clinically, TTFields have demonstrated a survival benefit in newly diagnosed GBM, as shown in the EF-14 randomized trial when added to maintenance temozolomide (TMZ)...Serial magnetic resonance imaging (MRI) was performed at approximately 1, 4, 7, 10,13 and 16 months (ongoing) after treatment initiation. The 54-year-old patient received radiotherapy (60 Gy) with lomustine-TMZ (CeTeG) and continuous TTFields but progressed with callosal spread after three CeTeG cycles... The depth and duration of control were unexpected after early failure of CeTeG + TTFields in MGMT+ GBM and in light of the typically short progression-free intervals reported with FGFR inhibition in glioma. We hypothesize that FGFR inhibition lowered a driver-mediated stress/DDR buffer, creating a transient vulnerable state in which TTFields impose orthogonal mitotic/DDR pressure, potentially intersecting with TACC3-linked spindle vulnerability, thereby limiting clonal escape and enabling durable control...."

Clinical • Brain Cancer • Glioblastoma • Glioneuronal Tumor • Oligodendroglioma • Oncology • Solid Tumor • FGFR3 • TACC3

Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma. (PubMed, N Engl J Med) - P3 | "Erdafitinib therapy resulted in significantly longer overall survival than chemotherapy among patients with metastatic urothelial carcinoma and FGFR alterations after previous anti-PD-1 or anti-PD-L1 treatment. (Funded by Janssen Research and Development; THOR ClinicalTrials.gov number, NCT03390504.)."

Biomarker • Clinical • Journal • Metastases • Observational data • P1 data • Retrospective data • Review • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

SOGUG-NEOWIN: A phase II, open-label, multi-centre trial evaluating the efficacy and safety of erdafitinib (ERDA) monotherapy and ERDA and cetrelimab (CET) as neoadjuvant treatment in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) and FGFR gene alterations (ESMO 2024) - P2 | "First patient screened on 31-Jan-2024. This trial would be the first to systematically address whether ERDA ± CET improves pCR in patients with FGFR+ MIBC."

Clinical • IO biomarker • Monotherapy • P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR • FGFR2

Asian subgroup analysis of the THOR phase III study: Erdafitinib versus chemotherapy in patients with advanced or metastatic urothelial cancer and selected fibroblast growth factor receptor alterations (ESMO Asia 2023) - P3 | "Methods Patients in cohort 1 were randomised to erdafitinib (8 mg once daily) or chemotherapy (vinflunine or docetaxel once every 3 weeks). Grade 3/4 treatment-related adverse events (AEs) and discontinuations due to treatment-related AEs occurred in 41% and 3% of patients on erdafitinib and 58% and 12% of those on chemotherapy, respectively. Conclusions In the Asian subgroup, erdafitinib showed improved survival and response vs chemotherapy, with no new safety concerns, consistent with the overall THOR population."

Clinical • Metastases • P3 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR

Erdafitinib or Erdafitinib Plus Cetrelimab for Patients With Metastatic Urothelial Carcinoma and FGFR Alterations: Final Results From the Phase II NORSE Study. (PubMed, J Clin Oncol) - "First-line erdafitinib monotherapy and erdafitinib plus cetrelimab demonstrated antitumor activity and a manageable safety profile in cisplatin-ineligible patients with mUC."

IO biomarker • Journal • P2 data • Dental Disorders • Genito-urinary Cancer • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Solid Tumor • Stomatitis • Urothelial Cancer • Xerostomia • FGFR • PD-L1

MARKER LESION STUDY OF ORAL ERDAFITINIB IN PATIENTS WITH INTERMEDIATE-RISK NON-MUSCLE–INVASIVE BLADDER CANCER WITH FGFR3/2 ALTERATIONS IN THOR-2: UPDATED COHORT 3 RESULTS (SUO 2023) - P2 | "In this marker lesion study of an FGFR-targeted therapy, erdafitinib demonstrated efficacy in all treated patients with IR NMIBC with FGFR alterations. Safety data were consistent with the known safety profile of erdafitinib."

Clinical • Bladder Cancer • Gastrointestinal Disorder • Genito-urinary Cancer • Metabolic Disorders • Nephrology • Oncology • Pain • Renal Disease • Retinal Disorders • Solid Tumor • Urothelial Cancer • Xerostomia • FGFR3

Tumor agnostic efficacy and safety of erdafitinib in patients (pts) with advanced solid tumors with prespecified fibroblast growth factor receptor alterations (FGFRalt) in RAGNAR: Interim analysis (IA) results. (ASCO 2022) - P2 | "RAGNAR data show, for the first time, evidence of efficacy for erda in heavily pretreated pts with a variety of hard to treat advanced FGFR+ malignancies, including glioblastoma, pancreatic, and salivary gland cancers. Safety was consistent with the known erda safety profile."

Clinical • Pan tumor • Brain Cancer • Gastrointestinal Disorder • Glioblastoma • Glioma • Oncology • Pancreatic Cancer • Pediatrics • Salivary Gland Cancer • Solid Tumor • Urothelial Cancer • FGFR • FGFR1 • FGFR3

UPDATED EFFICACY AND SAFETY OF ORAL ERDAFITINIB IN PATIENTS WITH BACILLUS CALMETTE-GUÉRIN–UNRESPONSIVE, HIGH-RISK NON-MUSCLE–INVASIVE BLADDER CANCER WITH FGFR3/2 ALTERATIONS IN THOR-2 COHORT 2 (SUO 2023) - P2 | "Treatment options for patients with bacillus Calmette-Guérin (BCG)-unresponsive CIS who refuse/are ineligible for radical cystectomy include pembrolizumab, intravesical chemotherapy, or nadofaragene firadenovec. Data from this trial provide first evidence of occurrence of FGFR alterations in CIS and demonstrate the promising and durable efficacy of an FGFR inhibitor such as erdafitinib in patients with BCG-unresponsive CIS with FGFR alterations. Safety data were consistent with the known safety profile of erdafitinib."

Clinical • Acute Kidney Injury • Bladder Cancer • Chronic Kidney Disease • Dental Disorders • Genito-urinary Cancer • Hypotension • Infectious Disease • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Retinal Disorders • Septic Shock • Solid Tumor • Stomatitis • Urothelial Cancer • Xerostomia • FGFR3

A first-in-human phase 1 study of LY3866288 (LOXO-435), a potent, highly isoform-selective FGFR3 inhibitor (FGFR3i) in advanced solid tumors with FGFR3 alterations: Initial results from FORAGER-1. (ASCO-GU 2025) - P1 | "LY3866288 is well-tolerated with robust clinical activity at multiple DLs, including in erdafitinib refractory mUC. Randomized dose optimization is ongoing and updated results will be presented."

Metastases • P1 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3 • TACC3

Erdafitinib (ERDA) vs ERDA plus cetrelimab (ERDA+CET) for patients (pts) with metastatic urothelial carcinoma (mUC) and fibroblast growth factor receptor alterations (FGFRa): Final results from the phase 2 Norse study. (ASCO 2023) - P1b | "Background: First-line (1L) therapy for cisplatin (cis)-ineligible pts with mUC remains an unmet need and includes alternative chemotherapy or anti-PD-(L)1 monotherapy for PD-L1 positive tumors. Combination ERDA+CET demonstrated clinically meaningful activity and was well tolerated. These results, in 1L cis-ineligible pts, support previously described activity of ERDA monotherapy in FGFRa mUC. The safety profile was consistent with the known profile for ERDA and CET with no additive toxicity for the combination."

Clinical • Metastases • P2 data • Dental Disorders • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Respiratory Diseases • Solid Tumor • Stomatitis • Urothelial Cancer • FGFR

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) (ESMO 2023) - P3 | "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 • Metastases • P3 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR • FGFR3

Primary analysis of TROPHY-U-01 cohort 2, a phase 2 study of sacituzumab govitecan (SG) in platinum (PT)-ineligible patients (pts) with metastatic urothelial cancer (mUC) that progressed after prior checkpoint inhibitor (CPI) therapy. (ASCO-GU 2023) - P2 | "Median number of prior therapies was 2 (range, 1-5); 50% received prior (neo)adjuvant PT, 18% received prior enfortumab vedotin, and 3% received prior erdafitinib. SG monotherapy demonstrated a high response rate with an overall manageable safety profile in PT-ineligible pts with mUC who progressed after CPI therapy. No new safety signals were observed. These data support further evaluation of SG in pts with mUC post CPI therapy."

Checkpoint inhibition • Clinical • Metastases • P2 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Erdafitinib in pediatric patients with advanced solid tumors with fibroblast growth factor receptor (FGFR) gene alterations: RAGNAR study pediatric cohort. (ASCO 2022) - P2 | "A follow-up phase will continue until death, withdrawal of consent, loss to follow-up, or end of study. As of January 2022, 3 patients have been enrolled."

Clinical • Brain Cancer • Glioma • Oncology • Pediatrics • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Urothelial Cancer • FGFR • FGFR2

SOGUG-NEOWIN: A phase 2, open-label, multicenter, multinational interventional trial evaluating the efficacy and safety of erdafitinib (ERDA) monotherapy and the combination of ERDA and cetrelimab (CET) as neoadjuvant treatment in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) harboring FGFR gene alterations. (ASCO 2025) - "As of January 21, 2025, 68 patients were pre-screened, 6 were FGFR2/3-positive, and 4 were enrolled. (EU CT Number 2024-512573-27-01)."

Clinical • IO biomarker • Monotherapy • P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Otorhinolaryngology • Pain • Retinal Disorders • Solid Tumor • Urothelial Cancer • FGFR • FGFR2

ETCTN 10483: Phase Ib trial of erdafitinib (E) combined with enfortumab vedotin (EV) following platinum and PD-1/L1 inhibitors for metastatic urothelial carcinoma (mUC) with FGFR3/2 genetic alterations (GAs). (ASCO-GU 2025) - P1 | "Enfortumab Vedotin (EV) is approved to treat patients with mUC following prior PBC and PD1/L1 inhibitors or as First-line therapy in combination with pembrolizumab. E+EV combination is feasible and preliminarily exhibits promising antitumor activity. Dose expansion is ongoing at RP2D dose of EV with E. Clinical trial information: NCT04963153"

IO biomarker • Metastases • P1 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

ETCTN 10483: Phase Ib trial of erdafitinib (E) combined with enfortumab vedotin (EV) following prior therapies for metastatic urothelial carcinoma (mUC) with FGFR3/2 genetic alterations (GAs). (ASCO-GU 2026) - P1 | "Enfortumab Vedotin (EV) is active as monotherapy post-platinum and in combination with pembrolizumab (EVP) as 1st line therapy in mUC. E+EV was feasible, tolerable, and showed high anti-tumor activity in FGFR3/2-altered mUC. The magnitude of response in this small cohort supports a biologic rationale for dual targeting of FGFR3 signaling and NECTIN-4–mediated antibody drug conjugate with further prospective evaluation of EVP and FGFR3-selective inhibitors in larger biomarker-defined studies."

Metastases • P1 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3