SUMMARY  

• THOR (BLC3001/NCT03390504) is an ongoing, phase 3, randomized, open-label, multicenter study evaluating the efficacy and safety of BALVERSA vs chemotherapy (docetaxel or vinflunine) or pembrolizumab in patients with metastatic or unresectable urothelial carcinoma (UC) and select FGFR alterations who had disease progression during or after 1 or 2 prior lines of therapy.^1,2
  • In an analysis of results from cohort 1 (n=266), the safety profiles were consistent with the known safety profiles of BALVERSA and chemotherapy. All grade and grade ≥3 stomatitis was reported in 65 (48.1%) and 11 (8.1%) patients in the BALVERSA arm vs 14 (12.5%) and 2 (1.8%) patients in the chemotherapy arm, respectively.
• BLC2001 (NCT02365597) is an ongoing, phase 2, open-label, multicenter study of BALVERSA in patients with locally advanced and unresectable or metastatic UC and prespecified FGFR genetic alterations (FGFR3 mutation or FGFR2/3 fusion).^3,4
  • In the final analysis (n=101), the safety profile remained similar to that in the primary analysis, with no new safety signals reported with a longer follow-up. The most common grade 3-4 treatment-emergent adverse events (TEAEs) included stomatitis (14%).³
• Follow dose modification guidelines for adverse reactions within product labeling. For medical management of stomatitis followed during the THOR and BLC2001 studies, refer to Table: Guidelines for Management of Stomatitis in the THOR Study and Table: Guidelines for Management of Stomatitis in the BLC2001 Study

CLINICAL DATA

To provide the most relevant information, the summary below is limited to information from the pivotal phase 3 (THOR/BLC3001; cohort 1) and phase 2 (BLC2001) studies in patients with locally advanced or metastatic UC and selected FGFR alterations.

THOR Study

THOR is an ongoing, phase 3, randomized, open-label, multicenter study evaluating the efficacy and safety of BALVERSA vs chemotherapy (docetaxel or vinflunine) or pembrolizumab in patients with metastatic or unresectable UC and selected FGFR gene alterations that has progressed during or after 1 or 2 prior lines of therapy.¹

In cohort 1, 266 patients were randomized 1:1 to receive an uptitration regimen of BALVERSA 8 mg once daily or chemotherapy (docetaxel 75 mg/m² intravenous [IV] every 3 weeks [Q3W] or vinflunine 320 mg/m² IV Q3W). Of all patients, 136 received BALVERSA 8 mg once daily and 130 received chemotherapy (82 assigned to docetaxel and 48 assigned to vinflunine).^1,2

Cohort 1 Analysis

In cohort 1, after a median of 15.9 months follow-up for efficacy and median duration of BALVERSA exposure of 4.8 months (range, 0.2-38.2), 136 patients received BALVERSA 8 mg once daily. The safety profiles in both arms were consistent with the known safety profiles of BALVERSA and chemotherapy.¹

• The incidence of stomatitis in the safety population is summarized in the Table: THOR Cohort 1 Safety Population: Incidence of Stomatitis.

BLC2001 Study

BLC2001 is an ongoing phase 2, open-label, multicenter study evaluating the use of BALVERSA in patients with locally advanced and unresectable or metastatic UC who had prespecified FGFR alterations (FGFR3 mutation or FGFR2/3 fusion) and disease progression during or following ≥1 line of prior systemic chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy, or were chemotherapy-naïve due to cisplatin ineligibility. Patients had tumor tissues with one of the following FGFR3 gene mutations: R248C, S249C, G370C, and Y373C, or one of the following FGFR fusions: FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7.⁵

The efficacy and safety analyses were described in patients who received an initial BALVERSA dose of 8 mg once daily, with uptitration to 9 mg once daily if serum phosphate levels assessed on day 14 were below the target of 5.5 mg/dL and there were no TRAEs.

Final Analysis

In the final analysis, after a median of 24 months follow-up for efficacy (interquartile range [IQR], 22.7-26.6) and median treatment duration of 5.4 months (IQR, 2.8-9), 101 patients were treated with an uptitration regimen of BALVERSA 8 mg once daily (2 patients enrolled after the clinical cutoff date for the primary analysis).³

• The safety profile of BALVERSA remained consistent with that of the primary analysis.
• No grade 4 adverse events (AEs) were considered related to BALVERSA, and no new TRAEs were observed with the longer follow-up. Overall, grade 3-4 TEAEs were reported in 72 (71%) patients, with one of the most common being stomatitis which occurred in 14 (14%) patients.

GUIDELINES FOR MANAGEMENT OF stomatitis IN THE THOR AND BLC2001 STUDies

Table: Guidelines for Management of Stomatitis in the THOR Study and Table: Guidelines for Management of Stomatitis in the BLC2001 Study summarizes interventions investigators in the THOR and BLC2001 studies were instructed to perform in order to manage stomatitis. These are not recommendations. Interventions should be based on patient presentation and the clinical judgment of the treating physician.

• General Prophylaxis^5,6:
  • Good oral hygiene
  • Use a soft toothbrush
  • Avoidance of spicy, acidic, hard, and hot food and beverages
  • Use of mild-flavored toothpastes
  • Use of saline-peroxide or salt and soda mouthwashes 3 or 4 times per day

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 07 November 2024.