Date: 2017-02-27
Type of information: Clinical research agreement
Compound: cabozantinib and atezolizumab
Company: Exelixis (USA - CA) Roche (Switzerland)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism:
- tyrosine kinase inhibitor/monoclonal antibody/immune checkpoint inhibitor . Cabozantinib is a kinase inhibitor that blocks abnormal kinase proteins involved in the development and growth of medullary cancer cells. Cabozantinib inhibits the activity of tyrosine kinases including MET, VEGFRs and AXL. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment. In April 2015, cabozantinib received Fast Track designation by the FDA for the potential treatment of advanced renal cell carcinoma patients who have received one prior therapy. Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib.
- On April 25, 2016 Cabometyx™ was approved by the FDA for the treatment of patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.
- Atezolizumab is an anti-PDL1 antibody designed to make cancer cells more vulnerable to the body’s immune system by interfering with a protein called PD-L1. PD-L1 is found on the surface of cells in tumours and is believed to act as a “stop sign,” preventing the immune system from destroying cancer cells. By inhibiting PD-L1, the antibody may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.
- The rationale for the combination is based on clinical and preclinical observations consistent with the ability of cabozantinib to promote an immunopermissive environment, which might present an opportunity for synergistic effects from combination treatment with immune checkpoint inhibitors and other immunotherapies.
Disease: locally advanced or metastatic solid tumors
Details:
- • On February 27, 2017, Exelixis announced a new collaboration with Roche on a phase 1b dose escalation study that will evaluate the safety and tolerability of cabozantinib, Exelixis’ tyrosine kinase inhibitor (TKI), in combination with atezolizumab, Roche’s anti-PD-L1 immunotherapy, in patients with locally advanced or metastatic solid tumors. Enrollment is scheduled to begin mid-year 2017; Exelixis will be the sponsor of the trial, and Roche will provide atezolizumab.
- Based on the dose-escalation results, the trial has the potential to enroll up to four expansion cohorts, including a cohort of patients with previously untreated advanced clear cell renal cell carcinoma and three cohorts of urothelial carcinoma, namely platinum eligible first-line patients, first- or second-line platinum ineligible patients, and patients previously treated with platinum-containing chemotherapy. Ipsen, Exelixis’ global partner for cabozantinib, except in the United States and Japan, will participate in this study and have access to the results for potential future development in its territories. Takeda may also participate in these and future studies and have access to the results to support potential future regulatory submissions in their territories, if they opt into their funding obligations under the respective collaboration agreement.
Financial terms:
Latest news: • On June 12, 2017, Exelixis announced the initiation of the dose-escalation stage of a phase 1b trial of cabozantinib in combination with atezolizumab in patients with locally advanced or metastatic urothelial carcinoma or renal cell carcinoma. The primary objective is to determine the optimal dose and schedule of daily oral administration of cabozantinib when given in combination with atezolizumab to inform the trial’s subsequent expansion stage.
Is general: Yes
