Abstract B22: Outcomes and genomic mutational profiling results in patients with cancers of the head and neck treated with dovitinib in the Signature Program

In the Signature Program, patients with advanced solid and hematologic cancers without other standard treatment options are enrolled in 1 of 8 tissue-agnostic, mutation-specific protocols. With no predetermined study sites, the program is able to bring the protocol to the patient through local enrollment via physician-directed genomic profiling of tumors. The primary endpoint of each study is clinical benefit, including complete response, partial response, or stable disease [SD], at 16 weeks by investigator assessment using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 or appropriate hematologic criteria. This novel design allows rapid matching of patients to a relevant targeted therapy. Dovitinib, a tyrosine kinase inhibitor with activity against multiple receptor tyrosine kinases, is currently in clinical development. Eighty patients were accrued in the dovitinib (TKI258) protocol from May 2013 to January 2015. Here, we describe a head and neck cancer subset of this population, including adenoid cystic carcinoma (ADC; n = 6), head and neck squamous cell carcinoma (HNSCC; n = 5), and salivary gland cancer (n = 1). The median age was 62 years, and patients had a median of 2 prior lines of therapy; 69% of patients were male, 85% were Caucasian, and 31% and 69% had an Eastern Cooperative Oncology Group performance status of 0 and 1, respectively. Patients met mutational inclusion criteria, with mutations in PDGFR α/ β , c-KIT , VEGFR2 , FGFR1 / 2 , and RET . There were no confirmed responses; however, 5 patients had SD on study. Of the 5 patients with SD, 4 had clinical benefit at 16 weeks (1 patient with SD at 8 weeks discontinued before 16 weeks). Consistent with other studies of dovitinib monotherapy, gastrointestinal adverse events (fatigue [69%], nausea [69%], diarrhea [54%], and vomiting [54%]) were the most common. In addition, pretreatment tissue biopsies from all patients were analyzed by a large multigene next-generation sequencing assay. Results to date indicate that the ADC cohort has a lower mutational load and fewer prior therapies than the HNSCC cohort. Further analysis of a correlation between clinical benefit and specific mutational profile is ongoing. Citation Format: Sarina A. Piha-Paul, James A. Knost, Luis E. Raez, Allen L. Cohn, Hussein A. Tawbi, Sudha Parasuraman, Barinder P. Kang, Renata M. Matys, Eric D. Slosberg. Outcomes and genomic mutational profiling results in patients with cancers of the head and neck treated with dovitinib in the Signature Program. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B22.