Research Papers:

A mutation-specific, single-arm, phase 2 study of dovitinib in patients with advanced malignancies

Matthew H. Taylor _, Ajjai S. Alva, Timothy Larson, Sebastian Szpakowski, Das Purkaystha, Alpesh Amin, Linda Karpiak and Sarina A. Piha-Paul

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Oncotarget. 2020; 11:1235-1243. https://doi.org/10.18632/oncotarget.27530

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Matthew H. Taylor1, Ajjai S. Alva2, Timothy Larson3, Sebastian Szpakowski4, Das Purkaystha5, Alpesh Amin5, Linda Karpiak5 and Sarina A. Piha-Paul6

1 Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA

2 Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA

3 USOR – Minnesota Oncology, Minneapolis, MN, USA

4 Novartis Institutes for Biomedical Research, Cambridge, MA, USA

5 Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

6 Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence to:

Matthew H. Taylor,email: [email protected]

Keywords: advanced malignancies; basket trial; dovitinib; histology-agnostic; mutation-specific

Received: November 11, 2019     Accepted: March 03, 2020     Published: April 07, 2020


Background: Receptor tyrosine kinases (RTKs) play key roles in tumorigenesis. The multi-RTK inhibitor dovitinib has demonstrated promising antitumor activity in multiple cancers.

Patients and Methods: In this phase 2, open-label, single-arm study, patients with advanced malignancies with RTK-pathway genetic aberrations whose disease progressed on/following standard treatment received dovitinib (500 mg/day; 5-days-on/2-days-off). The primary endpoint was clinical benefit rate (CBR; complete response, partial response [PR], or stable disease [SD] for ≥ 16 weeks).

Results: Of 80 patients enrolled, common tumors included gastrointestinal stromal tumors (GIST; 20.0%), colorectal cancer (CRC; 18.8%), and ovarian cancer (10.0%). Patients were heavily pretreated (median prior lines = 4; 67.5% had ≥ 3 prior lines). Genetic aberrations included cKIT (28.8%), FGFR3 (15.0%), and RET (15.0%). The CBR was 13.8%; one PR (GIST) and 10 SD (adenoid cystic [n = 3]; ovarian [n = 3]; GIST [n = 2]; CRC [n = 1]; gastroesophageal junction [n = 1]). The most common treatment-related adverse events were fatigue, diarrhea, nausea, and vomiting.

Conclusions: In this heterogeneous patient population, the safety profile was acceptable for dovitinib therapy. A subset of patients with RTK pathway-activated tumors experienced clinical benefit. However, the primary endpoint was not met, suggesting further refinement of predictive biomarkers is required.

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