Janssen presents results from Phase 1b/2 NORSE study in patients with metastatic or locally advanced urothelial carcinoma treated with erdafitinib in combination with cetrelimab

The Janssen Pharmaceutical Companies of Johnson & Johnson has announced results from the Phase 1b/2 NORSE (NCT03473743) study evaluating erdafitinib in combination with cetrelimab, an anti-programmed cell death protein 1 (PD-1) monoclonal antibody, compared to erdafitinib monotherapy in patients with locally advanced or metastatic urothelial carcinoma (mUC) with fibroblast growth factor receptor (FGFR)3 or FGFR2 genetic alterations who are ineligible for cisplatin, a current standard of care treatment for mUC.

The results were highlighted in an oral presentation at the European Society for Medical Oncology (ESMO) Annual Congress 2021 virtual meeting on earlier this month (Abstract #LBA27).

Preliminary findings suggest robust clinical activity and depth of response in patients treated with erdafitinib in combination with cetrelimab.

The overall safety of treatment with erdafitinib in combination with cetrelimab was generally consistent with erdafitinib monotherapy and aligned with the known safety profile of approved anti–PD-1 therapies.

At the time of analysis, the investigator-assessed objective response rate (ORR) in 19 patients treated with erdafitinib in combination with cetrelimab was 68 percent (95 percent confidence interval [CI]; 43-87), of which 21 percent (n=4) were complete responses (CR) and 47 percent were partial responses (PR).

The disease control rate (DCR) was 90 percent (95 percent CI; 67-99) for evaluable patients using the Response Evaluation Criteria in Solid Tumours Version (RECIST v1.1) criteria.

The ORR in 18 patients treated with erdafitinib monotherapy was 33 percent (95 percent CI; 13-59), in which one patient showed a CR and 28 percent (n=5) were PR. The DCR was 100 percent (95 percent CI; 82-100).

“People with advanced bladder cancer face an urgent need for new treatment options as current therapies are not suitable for all patients and do not always lead to adequate long-term outcomes,” said Dr Ignacio Durán, Medical Oncologist, Margues de Valdecilla University Hospital, Santander, Spain.

“The potential of precision oncology is to treat cancer patients using a personalised approach, tailored to their unique genetic composition, lifestyle and environment. The NORSE clinical study marks another important step forward in changing the prognosis for people living with specific genetic alterations associated with advanced bladder cancer.”

Fibroblast growth factor receptors are a family of receptor tyrosine kinases that can be activated by genetic alterations in a variety of tumour types, potentially leading to increased tumour cell growth and survival.

Approximately 20 percent of patients diagnosed with mUC have an FGFR genetic alteration. A current standard of care for mUC is cisplatin-based chemotherapy, however, more than 50 percent of patients with mUC may be ineligible for cisplatin treatment, underscoring a need for new treatment options.

Alternative options for patients with newly diagnosed mUC include different chemotherapy regimens or PD-1 inhibitors, which enhance T-cell immune responses against the tumour cells.

The findings presented at ESMO build upon the growing set of erdafitinib data. In 2019 the U.S. Food and Drug Administration (FDA) granted accelerated approval to erdafitinib, with a companion diagnostic, as a once-daily oral FGFR kinase inhibitor for patients with mUC that have susceptible FGFR3 and FGFR2 genetic alterations and who have progressed during, or following, at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

This indication is approved under accelerated approval based on tumour response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Within EMEA, erdafitinib has since been approved for use in Israel, Jordan and the Kingdom of Saudi Arabia.

The safety profile of erdafitinib in combination with cetrelimab (n=24) was generally similar to that of erdafitinib monotherapy (n=24), with the most common treatment-emergent adverse events (AEs) being hyperphosphataemia (erdafitinib in combination with cetrelimab vs erdafitinib monotherapy, 58 percent vs 58 percent), stomatitis (54 percent vs 63 percent), diarrhoea (42 percent vs 50 percent), dry mouth (58 percent vs 21 percent), dry skin (38 percent vs 21 percent) and anaemia (25 percent vs 25 percent).1 Grade 3-4 AEs occurred in 12 patients (50 percent) in the erdafitinib in combination with cetrelimab arm and 9 patients (38 percent) in the erdafitinib arm.1 In the erdafitinib in combination with cetrelimab arm, the most frequent Grade 3-4 AEs were stomatitis (n=3 [12.5 percent]), lipase increased (n=3 [12.5 percent]), and fatigue (n=2 [8.3 percent]); in the erdafitinib arm, these were anaemia (n=3 patients [12.5 percent]) and general physical health deterioration (n=3 [12.5 patients]).

“People living with bladder cancer often face a poor prognosis. This needs to change, and it is a challenge the scientific community can collectively overcome,” said Dr Catherine Taylor, Vice President, Medical Affairs for Europe, Middle East and Africa, Therapeutic Area Strategy, Jan-Cil Zug.

“Precision medicine in bladder cancer has the potential ambition to one day not only eliminate cancer, but in the meantime, to change what a cancer diagnosis means, giving back time and quality of life to people living with the disease.

“To date, there have been limited treatment options for patients living with specific genetic mutations, including FGFR alterations. The research presented today at ESMO paves the way for future solutions that are better tailored to the individual and address an area of significant unmet medical need.”

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