Date: 2017-06-12
Type of
information: Initiation of the trial
phase: 1b
Announcement: initiation of the trial
Company: Exelixis (USA - CA) Roche (Switzerland)
Product: cabozantinib and atezolizumab
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 urothelial carcinoma (UC), locally advanced or metastatic renal cell carcinoma
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
- This multicenter phase 1b, open-label study is divided in two parts: a dose-escalation phase and an expansion cohort phase. The dose-escalation phase will enroll 9 to 36 patients with inoperable, locally advanced, metastatic or recurrent urothelial carcinoma (including renal, pelvis, ureter, urinary bladder and urethra) after prior platinum-based therapy or renal cell carcinoma with or without prior systemic therapy. The starting dose of cabozantinib will be 40 mg daily and may be increased to 60 mg daily or decreased to 20 mg daily. All patients will receive the standard atezolizumab dosing regimen (1200 mg infusion once every 3 weeks).
- The secondary objectives of the dose-escalation stage are to evaluate the plasma pharmacokinetics of daily oral administration of cabozantinib when given in combination with atezolizumab and to assess safety of the combination therapy through the evaluation of incidence and severity of adverse events, including immune-related adverse events. Exploratory endpoints include the correlation of clinical outcome with immune cell, tumor cell and blood biomarker analyses. Once the recommended dose and schedule are determined, the trial will enroll four expansion cohorts, each with up to 30 patients, for a total of up to 120 patients with advanced or metastatic urothelial carcinoma or renal cell carcinoma. The primary objective in the expansion stage of the trial is to determine the objective response rate in each cohort.
- The three urothelial carcinoma expansion cohorts will enroll:
- 1) patients who have progressed on or after platinum-containing chemotherapy;
- 2) patients who are ineligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy for inoperable, locally advanced or metastatic disease; and
- 3) patients who are eligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy for inoperable, locally advanced or metastatic disease.
- The renal cell carcinoma expansion cohort will enroll patients with clear cell histology who have not had prior systemic anticancer therapy. (NCT03170960)
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
