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
Oral presentation at ESMO Annual Congress 2021 - featured in a late-breaking abstract - reports efficacy and safety of BALVERSA® in combination with a PD-1 inhibitor in bladder cancer
RARITAN, N.J., Sept. 17, 2021 /PRNewswire/ -- The Janssen Pharmaceutical Inc. Companies of Johnson & Johnson today announced results from the Phase 1b/2 NORSE (NCT03473743) study evaluating BALVERSA® (erdafitinib) in combination with cetrelimab, an anti-programmed cell death protein 1 (PD-1) monoclonal antibody, compared to BALVERSA® 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 Friday, September 17 (Abstract #LBA 27).1
Preliminary findings suggest robust clinical activity and depth of response in patients treated with BALVERSA® in combination with cetrelimab.1 The overall safety of treatment with BALVERSA® in combination with cetrelimab was generally consistent with BALVERSA® monotherapy and aligned with the known safety profile of approved anti–PD-1 therapies.1
At the time of analysis, the investigator-assessed objective response rate (ORR) in 19 patients treated with BALVERSA® 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).1 The disease control rate (DCR) was 90 percent (95 percent CI; 67-99) for evaluable patients using the Response Evaluation Criteria in Solid Tumors Version 1.1* (RECIST v1.1) criteria.1 The ORR in 18 patients treated with BALVERSA® monotherapy was 33 percent (95 percent CI; 13-59), in which one patient showed a CR and 28 percent (n=5) were partial responses. The DCR was 100 percent (95 percent CI; 82-100).1
"PD-1 inhibitors have become treatment options for many types of solid tumors, including bladder cancer. Now, as we learn more about the genetic factors that impact treatment outcomes, we are exploring new treatment approaches that may help patients with specific mutations, including FGFR-alterations and fusions," said Thomas Powles, MRCP, M.D., Professor of Uro-Oncology, Director of Barts Cancer Institute, London and principal study investigator.† "With this combination of erdafitinib and cetrelimab, we aim to change the tumor microenvironment to make it more receptive to PD-1 intervention."
Fibroblast growth factor receptors are a family of receptor tyrosine kinases that can be activated by genetic alterations in a variety of tumor types, potentially leading to increased tumor cell growth and survival.2 Approximately 20 percent of patients diagnosed with mUC have an FGFR genetic alteration.3,4 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.5 Alternative options for patients with newly diagnosed mUC include different chemotherapy regimens or PD-1 inhibitors, which enhance T-cell immune responses against the tumor cells.6
The findings presented at ESMO build upon the growing set of BALVERSA® data. In 2019 the U.S. Food and Drug Administration (FDA) granted accelerated approval to BALVERSA®, 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 tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.7
The safety profile of BALVERSA® in combination with cetrelimab (n=24) was generally similar to that of BALVERSA® monotherapy (n=24), with the most common treatment-emergent adverse events (AEs) being hyperphosphatemia (BALVERSA® in combination with cetrelimab vs BALVERSA® monotherapy, 58 percent vs 58 percent), stomatitis (54 percent vs 63 percent), diarrhea (42 percent vs 50 percent), dry mouth (58 percent vs 21 percent), dry skin (38 percent vs 21 percent) and anemia (25 percent vs 25 percent).1 Grade 3-4 AEs occurred in 12 patients (50 percent) in the BALVERSA® in combination with cetrelimab arm and 9 patients (38 percent) in the BALVERSA® arm.1 In the BALVERSA® 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 BALVERSA® arm, these were anemia (n=3 patients [12.5 percent]) and general physical health deterioration (n=3 [12.5 percent]).1
"As the first targeted treatment approved for patients with locally advanced or metastatic bladder cancer and FGFR3 or FGFR2 genetic alterations after platinum-based chemotherapy, we are encouraged by the data that continue to support the safety and efficacy of BALVERSA and its benefit for these patients with high unmet medical need. By investigating two active classes of drugs with BALVERSA and cetrelimab, our aim is to maximize the potential benefits of this combination approach for these patients," said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. "The continued development of BALVERSA reflects Janssen's ongoing commitment to offer more personalized therapy approaches for patients with bladder cancer, a disease where there is considerable need for more effective treatment using innovative approaches."
*RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumors, which is a standard way to measure how well solid tumors respond to treatment and is based on whether tumors shrink, remain the same or increase in size.8
About the NORSE Study9
About Urothelial Carcinoma
BALVERSA® is being studied in multiple clinical trials including the Phase 3 THOR (NCT03390504) study evaluating BALVERSA® versus standard of care, consisting of chemotherapy (docetaxel or vinflunine) or anti-PD-1 agent pembrolizumab, in participants with advanced urothelial cancer and selected FGFR aberrations with disease progression following one prior line of therapy; the Phase 2 THOR-2/BLC2003 study (NCT04172675) study examining BALVERSA® versus investigator choice of intravesical chemotherapy in participants who received Bacillus Calmette-Guérin and recurred with high risk non-muscle-invasive bladder cancer; and the Phase 2 RAGNAR (NCT04083976) study assessing BALVERSA® in patients with advanced solid tumors and FGFR genetic alterations.16,17,18
In 2008, Janssen entered into an exclusive worldwide license and collaboration agreement with Astex Pharmaceuticals to develop and commercialize BALVERSA®.
For more information, visit www.BALVERSA.com.
BALVERSA® IMPORTANT SAFETY INFORMATION
Warnings and Precautions
CSR/RPED was reported in 25% of patients treated with BALVERSA®, with a median time to first onset of 50 days. Grade 3 CSR/RPED, involving central field of vision, was reported in 3% of patients. CSR/RPED resolved in 13% of patients and was ongoing in 13% of patients at the study cutoff. CSR/RPED led to dose interruptions and reductions in 9% and 14% of patients, respectively, and 3% of patients discontinued BALVERSA®. Dry eye symptoms occurred in 28% of patients during treatment with BALVERSA® and were Grade 3 in 6% of patients. All patients should receive dry eye prophylaxis with ocular demulcents as needed.
Perform monthly ophthalmological examinations during the first 4 months of treatment and every 3 months afterwards, and urgently at any time for visual symptoms. Ophthalmological examination should include assessment of visual acuity, slit lamp examination, fundoscopy, and optical coherence tomography. Withhold BALVERSA® when CSR occurs and permanently discontinue if it does not resolve within 4 weeks or if Grade 4 in severity. For ocular adverse reactions, follow the dose modification guidelines [see Dosage and Administration (2.3)].
Hyperphosphatemia – Increases in phosphate levels are a pharmacodynamic effect of BALVERSA® [see Pharmacodynamics (12.2)]. Hyperphosphatemia was reported as adverse reaction in 76% of patients treated with BALVERSA®. The median onset time for any grade event of hyperphosphatemia was 20 days (range: 8–116) after initiating BALVERSA®. Thirty-two percent of patients received phosphate binders during treatment with BALVERSA®. Monitor for hyperphosphatemia and follow the dose modification guidelines when required [see Dosage and Administration (2.2, 2.3)].
Embryo-fetal Toxicity – Based on the mechanism of action and findings in animal reproduction studies, BALVERSA® can cause fetal harm when administered to a pregnant woman. In a rat embryo-fetal toxicity study, erdafitinib was embryotoxic and teratogenic at exposures less than the human exposures at all doses studied. Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with BALVERSA® and for one month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with BALVERSA® and for one month after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].
Most common adverse reactions including laboratory abnormalities ≥20%:
*Included within onycholysis. †Included within dry eye.
Use in Specific Populations
Please see the full Prescribing Information for BALVERSA®.
About the Janssen Pharmaceutical Companies of Johnson & Johnson
Learn more at www.janssen.com. Follow us at @JanssenUS and @JanssenGlobal. Janssen Biotech, Inc. and Janssen Research & Development, LLC are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
†Dr. Powles has been a paid consultant to Janssen; he has not been paid for any media work.
Cautions Concerning Forward-Looking Statements
1 Powles T et al. Erdafitinib (ERDA) or ERDA Plus Cetrelimab (CET) for Patients With Metastatic or Locally Advanced Urothelial Carcinoma (mUC) and Fibroblast Growth Factor Receptor Alterations (FGFRa): First Phase (Ph) 2 Results From the NORSE Study. 2021 European Society for Medical Oncology. September 16-21, 2021.
U.S. Medical Inquiries:
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