4702 - Phase I experience with rogaratinib in patients with head and neck cancer selected based on FGFR mRNA overexpression

Background

The orally administered fibroblast growth factor receptor (FGFR) inhibitor rogaratinib has shown promising efficacy in patients with urothelial cancer who were selected for treatment based on elevated tumor FGFR1-3 mRNA expression. Head and neck cancer (H&N) is an area of unmet medical need. Activation of the FGFR pathway has been suggested to be involved in head and neck cancer formation. A limited number of H&N cancer patients have been included in two phase I studies conducted with rogaratinib (NCT01976741 and NCT02592785). We describe here the collective experience from these phase-I studies for patients with H&N cancer treated at the recommended phase 2 dose (RP2D) of rogaratinib (800 mg bid).

Methods

Patients with advanced H&N cancer were selected based on high FGFR1-3 mRNA expression in formalin-fixed paraffin-embedded (FFPE) biopsy specimen as detected using RNA in situ hybridization and/or Nanostring™ assay. Pts were treated with rogaratinib 800 mg twice daily until tumor progression, intolerable toxicity, or withdrawal. Tumor response was assessed by RECIST, v1.1. Adverse events were reported using CTCAE v4.03 criteria.

Results

FFPE samples from 77 patients with H&N cancer were assessed for mRNA expression levels. Of the 71 valid samples, 38 (53%) were found to overexpress at least one FGFR mRNA. Patients who were FGFR mRNA positive were then screened for clinical eligibility. A total of 14 patients were treated at the RP2D of 800 mg bid and RECIST assessment is available for 10 patients. From the 10 evaluable patients, there were 2 partial responses, 6 patients had stable disease, 2 patients achieved SD > 6 months; 2 patients had progressive disease. Seven of 10 patients overexpressed FGFR3 mRNA subtype, including both patients with a PR. The median duration of treatment was 133 days. The most common adverse events included hyperphosphataemia and diarrhea.

Conclusions

Although a limited sample size, these results suggest that rogaratinib treatment of patients with FGFR mRNA-positive H&N cancer may be an area for further investigation.

Clinical trial identification

NCT01976741 and NCT02592785.

Legal entity responsible for the study

Bayer AG.

Funding

Bayer AG.

Editorial Acknowledgement

Disclosure

P.A. Cassier: Honoraria: Novartis, Roche, Blueprint Medicines, Amgen; Research funding: Novartis, Roche, Lilly, Blueprint Medicines, Bayer, AstraZeneca, Celgene, Plexxikon, Abbvie, BMS, Merck Serono, MSD, Taiho, Toray, Transgene. H. Nogai, C. Zhang, F. Sei, S. Bender, P. Ellinghaus: Employee: Bayer. All other authors have declared no conflicts of interest.