Newsworthy, late-breaking information from Web-based sources, professional societies, and government agencies Updated October 2018.
JAVELIN Renal 101 Update: Bavencio® (avelumab) plus Inlyta® (axitinib) significantly improved PFS in previously untreated patients with advanced RCC
DARMSTADT, GERMANY—Positive top-line results have been announced from the pivotal Phase III JAVELIN Renal 101 study evaluating bavencio® (avelumab) in combination with inlyta® (axitinib), compared with Sutent® (sunitinib) as initial therapy for patients with advanced renal cell carcinoma (RCC). As part of a planned interim analysis, an independent data monitoring committee confirmed that the trial showed a statistically significant improvement in progression-free survival (PFS) by central review for patients treated with the combination whose tumors had programmed death ligand-1‒positive (PD-L1+) expression greater than 1% (primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (secondary objective).
According to the statistical analysis plan, if PFS was statistically significant in the PD-L1+ subgroup, then PFS in the entire study population was to be analyzed for statistical significance. JAVELIN Renal 101 will continue as planned to the final analysis for the other primary endpoint of overall survival (OS). No new safety signals were observed, and adverse events for Bavencio, Inlyta and Sutent in this trial were consistent with known safety profiles for all three medicines. The alliance of Merck and Pfizer intends to pursue a regulatory submission in the US based on these interim results, and these results will be discussed with global health authorities. A detailed analysis will also be submitted for presentation at an upcoming medical congress.
In December 2017, the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for Bavencio in combination with Inlyta for treatment-naïve patients with advanced RCC. Despite available therapies, the outlook for patients with advanced RCC remains poor. Approximately 20% to 30% of patients are first diagnosed at the metastatic stage. The five-year survival rate for patients with metastatic RCC is approximately 12%.
JAVELIN Renal 101 is a global Phase III, multicenter, randomized (1:1) study investigating the efficacy and safety of Bavencio in combination with Inlyta as a first-line treatment option compared with Sutent monotherapy in 886 patients with advanced RCC across all risk groups. The primary objectives are to demonstrate that the combination is superior to Sutent monotherapy in prolonging PFS or OS in patients with PD-L1+ tumors. Bavencio was administered at 10 mg/kg IV every two weeks in combination with Inlyta at 5 mg orally twice daily; Sutent was administered at 50 mg orally once daily, four weeks on/two weeks off.
IKCS to be held in Miami, November 2-3
MIAMI—The 17th International Kidney Cancer Symposium, offering a comprehensive agenda and a broad spectrum of topics on diagnosis and treatment of renal cell carcinoma will be held at the National Doral Miami Hotel, November 2-3. The symposium, with an expected attendance of 400, is sponsored by the Kidney Cancer Association.
It will present analyses of emerging trends in RCC, Q&A sessions with key opinion leaders, and translational findings from clinical trials. Registration is available through the Kidney Cancer Association website:
Tivozanib hits another milestone with approval in Europe for advanced RCC
The European Commission (EC) has approved tivozanib (Fotivda) for the treatment of patients with advanced renal cell carcinoma (RCC), according to Aveo, the manufacturer of the pan-inhibitor of VEGF receptors, and its partner EUSA Pharma. The drug is specifically approved for the frontline treatment of adult patients with advanced RCC and for adults with advanced RCC who are VEGFR- and mTOR-inhibitor naïve following disease progression after one prior treatment with cytokine therapy.
The approval, which follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use, is based on the phase III TiVO-1 trial, in which tivozanib reduced the risk of disease progression or death by over 20% versus sorafenib (Nexavar) in patients with advanced RCC who received up to one prior line of therapy (excluding targeted agents). Researchers at Institut Gustave Roussy are currently evaluating tivozanib in combination with nivolumab (Opdivo) for patients with advanced RCC in the phase I/II dose escalation/expansion TiNivo trial. Additionally, results are anticipated in 2018 for the pivotal TIVO-3 trial, a randomized, controlled, multicenter, open-label study comparing tivozanib to sorafenib in patients with refractory advanced RCC.
Natera and Fox Chase Cancer Center to collaborate on kidney cancer study
SAN CARLOS, CA—Natera, Inc. has partnered with Fox Chase Cancer Center to assess the company’s Signatera™ (Research-Use Only) customized circulating tumor DNA (ctDNA) assay for recurrence monitoring of kidney cancer. The study will analyze biological specimens collected and banked from 49 patients diagnosed with kidney cancer—including a group whose cancer recurred and a group that did not recur after three years or more. The study will use Natera’s proprietary customized assay and next-generation sequencing (NGS)-based technology to determine whether Signatera (RUO) can be used to distinguish between the recurring and non-recurring kidney cancer cases. The study will be led by Philip Abbosh, MD, PhD, assistant professor, Molecular Therapeutics Program, Fox Chase Cancer Center.
“There is a paucity of data for circulating tumor DNA in kidney cancer. This research study will explore a novel approach for disease recurrence and treatment response monitoring in kidney cancer, since existing methods have limitations with sensitivity and specificity,” Dr Abbosh said. “Determining the relationship between kidney cancer genetic profiles and prognosis including recurrence using the Signatera assay has great potential to improve patient care by detecting cancer recurrence earlier, assisting adjuvant therapy decision-making, determining treatment effects, and assessing the need for intervention during follow-up.”
Discovery of kidney cancer driver could lead to new treatment strategy
CHAPEL HILL, North Carolina — University of North Carolina Lineberger Comprehensive Cancer Center scientists have uncovered a potential therapeutic target for kidney cancers that have a common genetic change. Scientists have known this genetic change can lead to an overabundance of blood vessels, which help feed nutrients to the tumors. Their latest finding shows a potential new cancer-driving pathway.
More than 90% of the most common type of kidney cancer have a genetic change that leads to the loss of an important tumor suppressor gene called VHL. In a study published in the journal Science, researchers identified a new downstream effect of this genetic change that is helping to drive kidney cancer: They found that a protein called ZHX2 over-accumulates in these cells and helps to turn on other signals involved in cancerous growth. Their findings suggest that ZHX2 is a potential new therapeutic target for clear cell RCC.
Targeted therpies block cell signals involved in abnormal blood vessel production — which is a downstream effect of VHL loss — that are part of the standard of care. Patients can show little response to these drugs or can develop resistance, so Zhang and his colleagues wanted to search for other targets that accumulate in cells lacking VHL function that help to drive the abnormal cancerous growth.The researchers created a screening technique to discover new molecules that might help drive cancer when VHL is lost. This led them to determine that kidney cancer cells lacking VHL usually had more ZHX2. By eliminating ZHX2 from their laboratory models, they inhibited cancer cell growth, invasion and the cancer’s spread. In addition, they saw that it was involved with signals that can help cancer cells grow. KCJ