Janseen Executive Committee Vice Chairman and Chief Scientific Officer Paul Stoffels.
Janssen Pharmaceutical Companies of Johnson & Johnson has announced the results of the phase 1b / 2 Norse study evaluating erdafitinib in combination with cetrelimab, a monoclonal antibody inhibitor of programmed cell death receptor 1 (PD-1), compared to erdafitinib as monotherapy in patients with locally advanced or metastatic urothelial carcinoma (mCU) and abnormalities in the fibroblast growth factor receptor FGFR3 or FGFR2 who are not eligible for cisplatin, a current gold standard treatment for mUC.
The results were presented during an oral presentation at the Annual Congress of the European Society for Medical Oncology (ESMO) 2021 held in virtual format on Friday, September 17. Preliminary data suggest that the combination of cetrelimab with erdafitinib offers a profound answer. The overall safety of erdafitinib treatment in combination with cetrelimab was generally consistent with that of erdafitinib monotherapy and in line with the known safety profile of approved anti-PD-1 therapies.RELATED
Evaluation of the response in solid tumors
At the time of analysis, the investigator-assessed objective response rate (ORR) in 19 patients treated with erdafitinib in combination with cetrelimab was 68%, of which 21% were complete responses and 47% were partial responses. The disease control rate (TBI) was 90% for evaluable patients using the response evaluation criteria in solid tumors. The ORR in 18 patients treated with erdafitinib in monotherapy was 33%, in which one patient showed CR and 28% were RP. The TCE was 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 results,” said Ignacio Durán, medical oncologist at the Marqués de Valdecilla University Hospital in Santander, Spain. “The potential of precision oncology is treating cancer patients using a personalized approach, tailored to their unique genetic makeup, lifestyle and environment. The Norse clinical study marks another important step towards changing the prognosis of people who have specific genetic alterations associated with advanced bladder cancer. “
New treatment options
Fibroblast growth factor receptors are a family of tyrosine kinase receptors that can be activated by genetic alterations in various types of tumors, potentially leading to increased proliferation and survival of tumor cells. Approximately 20% of patients diagnosed with CUm has a genetic alteration of FGFR2.
A current gold standard treatment for UCm is cisplatin-based chemotherapy, however, more than 50% of patients with UCm may not be eligible for treatment with cisplatin, highlighting the need for new treatment options. Alternative options for newly diagnosed patients with UC include different chemotherapy regimens or PD-1 inhibitors, both of which enhance immune responses of T lymphocytes against tumor cells.
Tumor response rate
The findings presented at the ESMO Congress add to the growing data set on erdafitinib. In 2019, the U.S. Food and Drug Administration (FDA) granted accelerated approval to erdafitinib, along with the add-on diagnostic test, as a once-oral FGFR tyrosine kinase inhibitor treatment. day for patients with UCm who have genetic alterations of FGFR3 and FGFR2 and who have progressed during or after at least one previous line of platinum chemotherapy, including neoadjuvant or adjuvant treatment with platinum-based chemotherapy received in the last 12 months.
This indication is approved under expedited approval based on tumor response rate. The continued approval of this indication may depend on the verification and description of the clinical benefit in confirmatory trials.
Adverse treatment events
The safety profile of erdafitinib in combination with cetrelimab was generally similar to that of erdafitinib monotherapy, with the most frequent adverse events (AE) arising during treatment being hyperphosphataemia (erdafitinib with cetrelimab versus erdafitinib alone, 58% vs 58%). , stomatitis (54% vs. 63%), diarrhea (42% vs. 50%), dry mouth (58% vs. 21%), dry skin (38% vs. 21%) and anemia (25% vs 25%).
Grade 3-4 AE occurred in 12 patients (50%) in the erdafitinib with cetrelimab group and 9 patients (38%) in the erdafitinib group. In the erdafitinib in combination with cetrelimab group, grade 3 AE -4 most frequent were stomatitis, elevated lipase, and fatigue; in the erdafitinib group, these were anemia and deterioration in general physical health.
“It is a challenge that we have to overcome”
“People with bladder cancer often face a poor prognosis. This has to change, and it is a challenge that the scientific community can collectively overcome, ”said Catherine Taylor, vice president of the Medical Department and Therapeutic Area Strategy for Europe, Middle East and Africa at Jan-Cil Zug.
“Precision medicine in bladder cancer has the ambitious potential to not only kill cancer one day, but in the meantime to change what a cancer diagnosis means, offering time and quality of life to people with the disease. To date, there have been limited treatment options for patients who have specific genetic mutations, including FGFR alterations. The research presented today at the ESMO Congress paves the way for future solutions that are better tailored to the individual and address a significant area of unmet medical need. ”
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