Combining Cabometyx (cabozantinib) with Opdivo (nivolumab) significantly extends survival, delays disease progression and increases the rate of positive responses compared to standard treatment with Sutent (sunitinib) among people with newly diagnosed advanced renal cell cancer, a pivotal Phase 3 trial shows.
The recent findings mean that the CheckMate -9ER trial (NCT03141177) met its primary goal of extending life without disease worsening, as well the secondary objectives of overall survival and increasing treatment responses.
“[W]e look forward to working with global health authorities to help bring this new combination regimen to previously untreated patients, a population that despite recent advances, remains in need of additional therapeutic options that extend survival,” Brian Lamon, PhD, said in a press release. Lamon is development lead, genitourinary cancers, at Opdivo’s developer, Bristol-Myers Squibb.
Cabometyx, developed by Exelixis, is a small molecule that blocks enzymes called tyrosine kinases, which are involved in several tumor processes, including the formation of new blood vessels, as well as tumor cell migration and invasiveness.
The therapy is approved for people with advanced kidney cancer, but evidence suggests that Cabometyx induces changes in tumors that make them more permissive to the entry of immune cells. This has lead researchers to believe that Cabometyx may work well in combination with immune checkpoint inhibitors such as Opdivo.
These immunotherapies work to block mechanisms that cancer cells use to dampen immune responses. In particular, Opdivo prevents the interaction between the PD-L1 protein on cancer cells with PD-1 on immune cells, which helps tumors evade immune attack. Opdivo is an approved therapy for people with advanced renal cell carcinoma — the most common type of kidney cancer in adults — who received prior therapies.
CheckMate -9ER was designed to compare a combination of these two therapies with standard care in 638 patients with advanced or metastatic disease who had not received prior therapies.
Enrolled across 145 clinical sites globally, participants were assigned randomly oral Cabometyx (40 mg) plus Opdivo — given via intravenous (into the bloodstream) infusions — or Pfizer‘s Sutent, taken by mouth.
The trial initially included a third group testing a combination of Cabometyx, Opdivo and Yervoy (ipilimumab) — another immune checkpoint inhibitor by Bristol-Myers — but the testing of that triple combination was discontinued.
Recent results revealed that patients receiving the double combo lived significantly longer without disease progression (progression-free survival), and had extended survival and higher response rates, compared with those on Sutent.
“We’re delighted that the trial met its primary endpoint of progression-free survival as well as the secondary endpoints of overall survival and objective response rate, demonstrating consistent benefit for the combination in previously untreated renal cell carcinoma patients,” said Gisela Schwab, MD, Exelixis’ president of product development and medical affairs, and chief medical officer.
“We look forward to our continued collaboration with Bristol Myers Squibb as we work toward regulatory filings in the near future,” Schwab said.
The Cabometyx-Opdivo combo also showed a favorable safety profile.
“If approved, this combination may become an important new first-line option for patients with metastatic renal cell carcinoma. We look forward to presenting detailed results at an upcoming congress,” said Toni Choueiri, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute (one of the trial’s locations).
Added Lamon: “We would like to thank the patients who participated in this trial, as well as the investigators and site personnel for their perseverance during the conduct of this study and in delivering this important result for patients in the midst of the COVID-19 pandemic.”