Dovitinib Seeking FDA Feedback for Potential RCC Indication


Oncology Venture has met with the FDA to discuss a potential path forward for the approval of dovitinib as a treatment for patients with renal cell carcinoma, according to a press release from the company.

Oncology Venture has met with the FDA to discuss a potential path forward for the approval of dovitinib as a treatment for patients with renal cell carcinoma (RCC), according to a press release from the company.1

The company is proposing that the application would seek approval for dovitinib in RCC in the third-line setting based on non-inferiority against sorafenib (Nexavar). During the meeting, the FDA indicated that such an NDA would be accepted and likely referred for review by the FDA’s Oncology Drugs Advisory Committee.

A companion diagnostic for dovitinib is also under development to select patients with a high likelihood of responding to the agent based on the genetic signature of their disease.

“We are excited to move towards US submission of our first oncology portfolio asset and appreciate FDA guidance in the filing process.” Steve Carchedi, CEO of Oncology Venture, said in a statement. “Renal cell cancer continues to have a high unmet need, and we hope that dovitinib, alone or together with a DRP companion diagnostic that we are validating for the drug, will provide patients with a more effective treatment.”

Dovitinib is a pan—tyrosine kinase inhibitor that was originally developed by Novartis. Oncology Venture in-licensed the agent and received the exclusive global rights to develop and commercialize the agent in April 2018.2

The company is seeking approval for dovitinib based on the results of a prior open-label, multicenter, randomized phase III trial in which dovitinib was studied in comparison with sorafenib in patients with metastatic RCC in the third-line setting.3

Patients in the study had at least a component of clear cell histology and had received one prior VEGF-targeted therapy and one prior mTOR inhibitor with disease progression within 6 months of the last therapy. Eligibility criteria also included a Karnofsky score of ≥70 and adequate hematologic, renal, and hepatic function. Those who had previously received either sorafenib or dovitinib and patients who had brain metastases, clinically significant heart disease, or uncontrolled hypertension were not eligible for enrollment in the study.

A total of 570 patients were randomized 1:1 to either dovitinib (n = 284) or sorafenib (n = 286). In the dovitinib arm, patients received 500 mg orally on a 5-days-on and 2-days-off schedule, whereas patients in the control arm received 400-mg oral sorafenib twice daily. All patients who received at least one dose of treatment (n = 564) were included in the safety analysis.

At a median follow-up of 11.3 months (range, 7.9-14.6), the median progression-free survival (PFS) by central radiologist review was 3.7 months (95% CI, 3.5-3.9) with dovitinib versus 3.6 months (95% CI, 3.5-3.7) with sorafenib (HR, 0.86; 95% CI, 0.72-1.04; one-sidedP= .063). According to investigator assessment, the median PFS was 3.9 months in each of the treatment arms. No subgroups of patients significantly favored dovitinib over sorafenib in terms of PFS.

The objective response rate was 4% in each arm with best responses of partial responses in 11 patients in each group. An additional 52% of patients in each arm achieved stable disease. More than half of the evaluable patients in the dovitinib group (51%) achieved reductions in tumor size compared with 46% in the sorafenib group.

Median overall survival was also similar between the 2 arms at 11.1 months (95% CI, 9.5-13.4) with dovitinib and 11.0 months with sorafenib (HR, 0.96; 95% CI, 0.75-1.22).

The median time to worsening of a patient’s Karnofsky performance status was 5.1 months with dovitinib versus 5.7 months with sorafenib (HR, 1.12; 95% CI, 0.87-1.45).

Dose changes were necessary due to adverse events (AEs) for 96 patients (34%) in the dovitinib arm compared with 199 (42%) in the sorafenib group. Dose interruptions were also necessary in 134 patients (48%) in the dovitinib arm and 99 patients (35%) in the sorafenib arm. The most common AEs requiring dose changes or interruptions in the dovitinib group were fatigue (11%), diarrhea (9%), nausea (6%), and vomiting (5%). With sorafenib, the most common AEs were palmar-plantar erythrodysesthesia (14%), fatigue (7%), diarrhea (5%), and reduced appetite (4%).

Common treatment-emergent grade 3/4 AEs with dovitinib included hypertriglyceridemia (14%), fatigue (10%), hypertension (8%), diarrhea (7%), dyspnea (6%), anemia (5%), and an increase in gamma-glutamyltransferase levels (5%). In the sorafenib group, common grade 3/4 treatment-emergent AEs included hypertension (17%), fatigue (8%), dyspnea (7%), palmar-plantar erythrodysesthesia (6%), and anemia (6%). Serious treatment-emergent AEs were seen in 48% and 39% of patients, respectively, in the dovitinib and sorafenib groups, and were most often dyspnea.

Notably, treatment-emergent acne-like rashes were reported in 30% of patients in the dovitinib group at any grade. Hypothyroidism was also observed in 5% of patients in the dovitinib arm versus 3% in the sorafenib group and ≤20% changes from baseline in cardiac ejection fraction were seen in 6% of patients in each group.

Four potential treatment-related deaths were reported in the dovitinib group and one in the sorafenib group.

Dovitinib has also shown antitumor activity in metastatic breast cancer, hepatocellular cancer, endometrial cancer, and gastrointestinal stromal tumors. The agent has also been explored in combination with immune checkpoint inhibitors.


  1. Oncology Venture receives feedback from U.S. FDA on potential approval pathway for Dovitinib [press release]. Horsholm, Denmark: Oncology Venture A/S; March 20, 2020. Accessed March 20, 2020.
  2. MPI — Oncology Venture exercises option to inlicense Dovitinib a Phase 3 Multi Tyrosine Kinase Inhibitor [press release]. Horsholm, Denmark: Oncology Venture A/S; April 9, 2018. Accessed March 20, 2020.
  3. Motzer RJ, Porta C, Vogelzang NJ, et al. Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial.Lancet Oncol.2014;15(3):286-296. doi: 10.1016/S1470-2045(14)70030-0.
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