Javlor (vinflunine) / Pierre Fabre - 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

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

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

Use of early dynamics of clinical and laboratory parameters to predict resistance in patients with metastatic urothelial carcinoma receiving post-platinum atezolizumab (AACR 2024) - "We investigated readily available baseline and EOT variables from the phase 3 clinical trial IMvigor211, which compared atezolizumab, a PD-L1 inhibitor, with chemotherapy (taxane or vinflunine), in patients with mUC who have progressed on platinum-based chemotherapy. Of 931 patients in IMvigor211, 902 were evaluable for our analysis...The strongest baseline predictors are PD-L1 expression, prior treatment with both cisplatin and carboplatin, and the presence of liver metastases... Our prediction models employing readily available and affordable EOT clinical and laboratory variables robustly (AUC 0.83) identified patients with early resistance and may inform patient-specific therapeutic decisions. Further validation is required."

Clinical • IO biomarker • Metastases • Oncology • Solid Tumor • Urothelial Cancer

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

Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. (PubMed, N Engl J Med) - P3 | "Enfortumab vedotin significantly prolonged survival as compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based treatment and a PD-1 or PD-L1 inhibitor. (Funded by Astellas Pharma US and Seagen; EV-301 ClinicalTrials.gov number, NCT03474107.)."

Journal • Oncology • Solid Tumor • Urothelial Cancer

Efficacy and safety of pembrolizumab (pembro) monotherapy in East Asian patients (pts) with urothelial carcinoma (UC) in KEYNOTE-045 or KEYNOTE-052 (ESMO Asia 2022) - P2, P3 | "Pts in KEYNOTE-045 were randomly assigned 1:1 to receive investigator's choice of chemotherapy (chemo; paclitaxel [175 mg/m2 IV Q3W], docetaxel [75 mg/m2 IV Q3W], or vinflunine [320 mg/m2 IV Q3W]) or pembro (200 mg IV Q3W up to 2 y). Conclusions In this exploratory analysis, pembro appeared to show generally similar antitumor activity and safety between East Asian pts and the global population for both the 1L setting for cisplatin-ineligible pts and 2L setting for platinum-refractory pts. Small sample size may limit the generalizability of the findings Table: 136MO KEYNOTE-045 KEYNOTE-052 East Asian pts Global population East Asian pts Global population Pembro (n = 62) Chemo (n = 51) Pembro (n = 270) Chemo (n = 272) Pembro (N = 20) Pembro (N = 370) ORR, % (95% CI) 19 (10.4-31.4) 16 (7.0-28.6) 22 (17.1-27.3) 11 (7.6-15.4) 10 (1.2-31.7) 29 (24.3-33.8) Best response, n (%) CR 5 (8) 2 (4) 27 (10) 8 (3) 1 (5) 35 (9) PR 7 (11) 6 (12) 32 (12) 22 (8) 1 (5) 72 (19)..."

Clinical • Monotherapy • Oncology • Solid Tumor • Urothelial Cancer

Sacituzumab govitecan in advanced urothelial carcinoma: TROPiCS-04, a phase III randomized trial. (PubMed, Ann Oncol) - P3 | "SG did not result in a significant improvement in OS or PFS compared with TPC in pretreated aUC, although SG activity was demonstrated by a higher ORR. Early toxicity-related complications with SG may have impacted efficacy outcomes."

Journal • P3 data • Bladder Cancer • Febrile Neutropenia • Genito-urinary Cancer • Hematological Disorders • Infectious Disease • Neutropenia • Oncology • Solid Tumor • Urothelial Cancer

TROPiCS-04, a randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (CT) in pretreated advanced urothelial carcinoma (aUC): Overall survival (OS) and safety analysis (ESMO Asia 2024) - P3 | "Methods Pts with aUC who received prior platinum (PT)-based CT and checkpoint inhibitor therapy were randomized 1:1 to receive SG 10 mg/kg intravenously (IV) on days (D) 1 and 8 of 21-D cycles or treatment (tx) of physician's choice (TPC; paclitaxel 175 mg/m 2 IV, docetaxel 75 mg/m 2 IV, or vinflunine 320 mg/m 2 IV, on D1 of 21-D cycles). Safety data were consistent with the known toxicity profile of SG across tumor types, except for increased rates of neutropenic complications in this high-risk population. These AEs may have impacted overall results and could possibly be mitigated by increasing use of primary G-CSF prophylaxis."

Clinical • Late-breaking abstract • Metastases • P3 data • Oncology • Solid Tumor • Urothelial Cancer

Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up. (PubMed, Ann Oncol) - P2, P3 | "With approximately 5 years of follow-up, pembrolizumab monotherapy continued to demonstrate durable efficacy with no new safety signals in patients with platinum-resistant metastatic UC and as first-line therapy in cisplatin-ineligible patients. Clinical trial registry and ID: ClinicalTrials.gov, NCT02256436 (KEYNOTE-045) and NCT02335424 (KEYNOTE-052)."

Journal • Immune Modulation • Inflammation • Oncology • Solid Tumor • Urothelial Cancer

Phase 3 THOR study: Results of erdafitinib (erda) versus chemotherapy (chemo) in patients (pts) with advanced or metastatic urothelial cancer (mUC) with select fibroblast growth factor receptor alterations (FGFRalt). (ASCO 2023) - P3 | " Pts (≥18 y) with unresectable advanced/mUC and select FGFR3/2alt (mutations/fusions), ECOG performance status 0-2, adequate organ function, progression on/after prior systemic therapy (tx) that included an anti-PD-(L)1 agent, and ≤2 prior lines of tx were randomized 1:1 to receive erda (8 mg with pharmacodynamically guided uptitration to 9 mg on day 14) QD or investigator’s choice of chemo (docetaxel or vinflunine) Q3W until disease progression or intolerable toxicity. In pts with FGFRalt advanced/mUC after prior treatment with PD-(L)1, erda significantly improved OS, PFS, and ORR vs investigator’s choice of chemo. Erda toxicity was consistent with the known safety profile. These results support the role of erda to treat pts with FGFRalt mUC after PD-(L)1 tx."

Clinical • IO biomarker • Late-breaking abstract • Metastases • P3 data • Genito-urinary Cancer • Oncology • Retinal Disorders • Solid Tumor • Urothelial Cancer • FGFR • FGFR3 • PD-L1

Impact of prior chemotherapy (Chemo) on pembrolizumab (Pembro) response in urothelial cancer (UC): Exploratory analysis of the phase III KEYNOTE-045 study (ESMO 2022) - P3 | "Methods Pts with metastatic UC who progressed after platinum chemo were randomly assigned 1:1 to pembro 200 mg Q3W or investigator's choice of paclitaxel, docetaxel, or vinflunine. OS and ORR with pembro were evaluated by best response to prior therapy before enrollment (investigator assessment) and by whether prior chemo was cisplatin- or non–cisplatin-based...While pts with PD as best response to chemo had numerically lower survival, pts still responded and benefited from pembro treatment. Limitations included that the responses based on investigator assessment of the prior chemo response were not reconciled by the Sponsor using imaging data and the small sample size."

P3 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Long-term outcomes in EV-301: 24-month findings from the phase 3 trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma. (ASCO 2022) - P3 | " In EV-301 (NCT03474107), patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who had received a prior platinum-containing chemotherapy and had disease progression during or after PD-1/L1 inhibitor treatment were randomized 1:1 to receive either EV 1.25 mg/kg on Days 1, 8, and 15 of each 28-day cycle or investigator-chosen standard chemotherapy with docetaxel, paclitaxel, or vinflunine. EV continues to show significant and consistent survival advantage over standard chemotherapy in patients with treatment-experienced la/mUC. No new safety signals were identified. With robust clinical benefit and a tolerable safety profile, EV maintains its place as a standard of care for this aggressive disease."

Clinical • P3 data • Oncology • Solid Tumor • Urothelial Cancer • NECTIN4

Impact of dose reductions on the efficacy of erdafitinib (Erda) in patients (Pts) with advanced or metastatic urothelial carcinoma (mUC): A post-hoc analysis of the phase III THOR study cohort-1 evaluating Erda versus chemotherapy (Chemo) (ESMO 2025) - P3 | "Methods Pts with advanced/mUC with FGFR3/2 alterations, ECOG PS 0–2, who progressed after 1–2 prior therapy (including anti-PD-[L]1) were randomized 1:1 to erda (8 mg per day with option of uptitration to 9 mg on day 14) or investigator's choice of chemo (docetaxel or vinflunine). Table: 3092P ERDA Randomized population ERDA Safety population a Number of dose reductions 0 1 ≥2 n 136 66 33 36 OS Median (95% CI), mo 12.1 (10.3, 16.4) 10.0 (8.1, 10.9) 10.3 (8.5, 16.8) 23.3 (18.2, NE) 6-mo rate, % 85 77 87 97 12-mo rate, % 51 36 43 81 Median PFS (95% CI), mo 5.6 (4.4, 5.7) 4.2 (2.8, 5.4) 5.6 (4.0, 5.9) 10.8 (5.8, 13.7) Confirmed ORR, n (%) 62 (45.6) 13 (19.7) 16 (48.5) 19 (52.8) a All randomized pts who received ≥1 dose of Erda. Conclusions Dose reductions of Erda due to TEAEs were common and did not seem to impact efficacy, highlighting the importance of proactive toxicity management to optimize both tolerability and clinical outcomes."

Clinical • Metastases • P3 data • Retrospective data • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

FORT-1: Phase II/III Study of Rogaratinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Selected Based on FGFR1/3 mRNA Expression. (PubMed, J Clin Oncol) - P2/3 | "To our knowledge, these are the first data to compare FGFR-directed therapy with chemotherapy in patients with FGFR-altered UC, showing comparable efficacy and manageable safety. Exploratory testing suggested FGFR3 DNA alterations in association with FGFR1/3 mRNA overexpression may be better predictors of rogaratinib response."

Journal • P2/3 data • Oncology • Solid Tumor • Urothelial Cancer • FGFR1 • FGFR3

FDA Approval Summary: Erdafitinib for FGFR3-Altered Locally Advanced or Metastatic Urothelial Carcinoma. (PubMed, Clin Cancer Res) - P3 | "Substantial evidence of effectiveness was obtained from BLC3001 (THOR, NCT03390504) Cohort 1, which was an open-label trial in which 266 patients with FGFR3-altered la/mUC were randomized 1:1 to receive erdafitinib (8 mg once daily with potential up-titration to 9 mg) versus chemotherapy (docetaxel 75 mg/m2 every 3 weeks or vinflunine 320 mg/m2 every 3 weeks) until disease progression or unacceptable toxicity. Based on BLC3001 Cohort 2 results showing no OS benefit of erdafitinib versus pembrolizumab (HR 1.18, 95% CI: 0.92, 1.51), the approval includes a limitation of use: erdafitinib is not recommended for the treatment of patients who are eligible for and have not received prior PD-(L)1 inhibitor therapy. This article summarizes the data and the FDA thought process supporting traditional approval of erdafitinib, including the rationale for not requiring specific types of prior systemic therapy in the indication statement."

FDA event • Journal • PD(L)-1 companion diagnostic • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

A clinical trial of sacituzumab tirumotecan to treat urothelial cancer (MK-2870-031) (clinicaltrialsregister.eu) - P2/3 | N=265 | Recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2/3 trial • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

TroFuse-031: A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) to Treat Urothelial Cancer (MK-2870-031) (clinicaltrials.gov) - P3 | N=590 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

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=630 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC | Phase classification: P=N/A ➔ P3

Phase classification

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=631 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Mar 2023 ➔ Oct 2023

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

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=631 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2021 ➔ May 2021

Trial completion date

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=631 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Nov 2021 ➔ Feb 2027 | Trial primary completion date: Nov 2020 ➔ Apr 2024

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

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=631 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Apr 2024 ➔ Oct 2033

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

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=631 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Feb 2027 ➔ Apr 2024

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

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=631 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open