Exelixis is commencing a Phase III pivotal trial to evaluate cabozantinib (CABOMETYX) for the treatment of patients with previously untreated advanced renal cell carcinoma (RCC).
As part of the trial, cabozantinib will be evaluated in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) versus nivolumab and ipilimumab provided by Bristol-Myers Squibb as The mechanisms of action of single-agent cabozantinib and the combination of nivolumab and ipilimumab are complementary and each has demonstrated efficacy in advanced renal cell carcinoma.
Exelixis Product Development and Medical Affairs president and chief medical officer Gisela Schwab said: “Clinical observations suggest cabozantinib promotes an immune-permissive environment, which could present an opportunity for additive or synergistic effects with immune checkpoint inhibitors.
“The further combination of these agents as a triplet regimen may offer promise to previously untreated patients with the intermediate or poor-risk disease, who are known to have poor treatment outcomes. For the multi-center, randomized, double-blinded, controlled Phase III pivotal trial COSMIC-313 about 676 patients are expected to be enrolled at 150 sites across the globe.
Patients will be randomized 1:1 to cabozantinib’s experimental arm in combination with nivolumab and ipilimumab and to the control arm of nivolumab and ipilimumab in combination with matched placebo.
Design of this trial was informed by results from the ongoing Phase Ib study of cabozantinib plus nivolumab with or without ipilimumab in patients with previously treated advanced genitourinary cancers, including RCC.
Cabozantinib Shows Promising Activity in Osteosarcoma and Ewing Sarcoma
Cabozantinib demonstrated efficacy in advanced osteosarcoma and Ewing sarcoma, according to the results of 2 phase 2 trials presented at the ESMO 2018 Congress in Munich, Germany.
The outcomes for patients with relapsed and unresectable osteosarcoma and Ewing sarcoma remain poor, with no approved agents available in this setting. Preclinical studies, however, suggest that MET inhibition or antiangiogenic agents may have efficacy in these diseases. These studies sought to evaluate the efficacy and safety of cabozantinib in advanced osteosarcoma and Ewing sarcoma.
The 2 multicenter, single-arm, 2-stage phase 2 trials treated 90 adults and children with advanced osteosarcoma or Ewing sarcoma with cabozantinib once daily until progressive disease or unacceptable toxicity. The primary endpoints were a 6-month objective response (OR) and nonprogression in the osteosarcoma cohort and OR in the Ewing sarcoma cohort.
The study is considered positive if 5 patients each with osteosarcoma or Ewing sarcoma experience an OR, or if 16 patients with osteosarcoma are free from progression at 6 months. At baseline, the median age of study participants was 35 years and 33 years for the osteosarcoma and Ewing sarcoma cohorts, respectively, and the median lines of previous therapies was 3 and 4, respectively.
In the osteosarcoma cohort, 45.2% of patients experienced tumor shrinkage, including 11.9% who experienced partial responses (PRs) and 33.3% who saw disease stabilization. The 6-month nonprogression rate was 33.3%.
In the Ewing sarcoma cohort, tumor shrinkage occurred in 57.6% of patients, including 27.7% with PRs and 30.3% with disease stabilization. The 6-month nonprogression rate was 24.2%.
At least 1 adverse event occurred in 96% of patients.
The authors concluded that these data suggest that cabozantinib has “meaningful clinical activity in osteosarcoma and Ewing sarcoma patients with heavily pretreated advanced disease.” They noted that the primary endpoints were met in both cohorts.
Information Source: Cancer Therapy Advisor, Google, Internet.