An early study looking at the combination of the ALK1 inhibitor dalantercept plus axitinib showed clinical activity in patients with advanced renal cell carcinoma (RCC), according to the results of the DART study published in Clinical Cancer Research.
“This study demonstrates that the combination of dalantercept plus axitinib is overall well tolerated with a generally non-overlapping safety profile in patients with previously treated RCC,” wrote researcher Martin H. Voss, MD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues.
Patients in the study were assigned to dalantercept 0.6 mg/kg, 0.9 mg/kg, or 1.2 mg/kg every 3 weeks plus axitinib 5 mg orally twice daily until disease progression or intolerance. Fifteen patients were enrolled in the dose-escalation portion of the study, and 14 in the expansion cohorts. All patients had received at least one prior VEGFR tyrosine kinase inhibitor and up to three prior cancer-directed therapies.
There was an overall objective response rate (ORR) of 25%—all partial responses. In addition, 60.7% of patients had stable disease, while 14.3% of patients had disease progression. Responses occurred at all dose levels of dalantercept.
Fourteen patients maintained disease control for 6 months or longer, for a disease control rate of 50%. The researchers noted that the majority of patients with a partial response had at least two prior therapies.
The median progression-free survival was 8.3 months. Three-quarters of patients achieved a decrease in target lesions and 29% remained on therapy for 1 year or longer.
“While it is not possible to say to what extent these findings reflect antitumor effect of axitinib vs the combination, these outcomes compare favorably to the historical ORR of 11% and median progression-free survival of 4.8 months reported for axitinib in patients pretreated with sunitinib,” the researchers wrote.
The combination was generally well-tolerated, according to the researchers. Overall, there were no dose-limiting toxicities or grade 4/5 treatment-related adverse events. The most commonly seen adverse events were fatigue, diarrhea, peripheral edema, epistaxis, pericardial effusion, increased creatinine, and telangiectasia. Epistaxis, peripheral edema, and creatinine rise occurred with a greater incidence in those patients assigned to higher doses.
The 0.9 mg/kg dose was selected for further development.