Janssen Announces Phase 1b/2 NORSE Study Results: BALVERSA® (erdafitinib) Plus Cetrelimab Achieves 68% Overall Response Rate in FGFR-Altered Metastatic Urothelial Carcinoma

September 21, 2021 /BioonBIOON/ -- Johnson & Johnson (JNJ)'s Janssen Pharmaceuticals recently at the 2021 European MedicalTumorResults of the Phase 1b/2 NORSE study (NCT03473743) were presented at the European Society for Medical Oncology (ESMO) virtual congress. Conducted in patients with cisplatin-ineligible, locally advanced or metastatic urothelial carcinoma (mUC) harboring fibroblast growth factor receptor (FGFR) FGFR3 or FGFR2 genetic alterations, the study is evaluating the combination regimen of the FGFR kinase inhibitor Balversa (erdafitinib) and the PD-1 inhibitor cetrelimab, compared with Balversa monotherapy. Cisplatin is currently a standard-of-care treatment for mUC.

Preliminary research results indicate that,The Balversa + cetrelimab regimen demonstrated robust clinical activity and depth of response in patients,The overall safety profile was generally consistent with Balversa monotherapy and with the known safety profile of approved anti-PD-1 therapies.

At the time of data analysis, among the 19 patients treated with Balversa + cetrelimab, the investigator-assessedThe objective response rate (ORR) was 68% (95% CI: 43–87), with 21% (n=4) achieving complete response (CR) and 47% achieving partial response (PR).. Evaluated according to the response assessment criteria of the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), the disease control rate (DCR) was 90% (95% CI: 67–99). Among 18 patients who receivedAmong patients receiving Balversa monotherapy, the ORR was 33% (95% CI: 13–59), including 1 patient with CR and 28% (n=5) with PR., DCR was 100% (95% CI: 82-100).

In this study, the safety of Balversa in combination with cetrelimab (n=24) was generally comparable to that of Balversa monotherapy (n=24). The most common treatment-emergent adverse events (AEs) were hyperphosphatemia (Balversa + cetrelimab group vs. Balversa monotherapy group: 58% vs. 58%), stomatitis (54% vs. 63%), diarrhea (42% vs. 50%), dry mouth (58% vs. 21%), dry skin (38% vs. 21%), andAnemia(25% vs 25%). Grade 3–4 adverse events occurred in 12 patients (50%) in the Balversa + cetrelimab arm and 9 patients (38%) in the Balversa monotherapy arm. The most common Grade 3–4 adverse events in the Balversa + cetrelimab arm were stomatitis (n=3 [12.5%]), increased lipase (n=3 [12.5%]), and fatigue (n=2 [8.3%]); in the Balversa arm, they were anemia (n=3 [12.5%]) and general health deterioration (n=3 [12.5%]).

Thomas Powles, Principal Investigator of the study, Professor of Urothelial Oncology and Director of the Barts Cancer Institute in London, stated: “PD-1 inhibitors have become a treatment option for multiple solid tumors, including bladder cancer. Now, as our understanding of factors affecting treatment outcomesGeneticsBased on our understanding of these factors, we are exploring new treatments that may benefit patients with specific mutations, including FGFR alterations and fusions.Through combination therapy with Balversa and cetrelimab, we aim to transformTumormicroenvironment, making it more susceptible to PD-1 intervention。”

Janssen Research & Development, LLC# TumorCraig Tendler, M.D., Vice President of Late-Stage Development and Global Medical Affairs, stated: “As the first targeted therapy approved for patients with locally advanced or metastatic bladder cancer who have received platinum-based chemotherapy and harbor FGFR3 or FGFR2 genetic alterations, we are encouraged by the data that continue to support the safety and efficacy of Balversa, as well as the benefits it provides to these patients with a high unmet medical need. Our goal is to combine two active agents (Balversa and cetrelimab) to maximize the potential benefit of the combination therapy for these patients.”

Fibroblast growth factor receptor (FGFR) is a family of receptor tyrosine kinases that can be activated by genetic alterations in various tumor types, which may lead to increased tumor cell growth and survival. Urothelial carcinoma (UC) is the most common type of bladder cancer, accounting for more than 90% of all bladder cancer cases. Approximately 20% of patients with mUC harbor FGFR genetic alterations. Currently, the standard therapy for mUC is cisplatin-based chemotherapy; however, more than 50% of mUC patients may be ineligible for cisplatin treatment, underscoring the need for new treatment options. NewDiagnosisAlternative options for mUC patients include different chemotherapy regimens or PD-1 inhibitors, the latter of which can enhance T cells againstTumorCellular immune response.

Balversa is a once-daily oral FGFR kinase inhibitor approved in April 2019: for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) harboring specific FGFR genetic alterations. Specifically: for adult patients with locally advanced or metastatic UC harboring susceptible FGFR3 or FGFR2 genetic alterations, whose disease has progressed during or following at least one line of platinum-containing chemotherapy (including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy).

It is worth mentioning that,Balversa is the first FGFR kinase inhibitor approved by the US FDA.Further approval of the drug's indications will be contingent upon the verification and characterization of clinical efficacy in confirmatory studies. Previously,FDABreakthrough Therapy Designation (BTD) and Priority Review designation were granted for Balversa in March 2018 and September 2018, respectively.

Balversa is specifically approved for the treatment ofTumormUC patients harboring FGFR3 or FGFR2 genetic alterations. In the United States, it is estimated that up to 3,000 UC patients harboring FGFR genetic alterations are diagnosed annually. FGFR genetic alterations can beFDAApproved CompanionDiagnosisTest kit detection. The current 5-year survival rate for patients with stage IV metastatic bladder cancer, in which cancer cells have spread to distant sites in the body, is 6%. (Bioon.com)

Original Source:Janssen Presents Results from Phase 1b/2 NORSE Study in Patients with Metastatic or Locally Advanced Urothelial Carcinoma Treated with BALVERSA? (erdafitinib) in Combination with Cetrelimab, a PD-1 Inhibitor