Exelixis Initiates Cabozantinib-Tecentriq Combination Trial

 | Jun 13, 2017 05:32AM ET

Exelixis, Inc. (NASDAQ:EXEL) announced that it initiated the dose-escalation stage of a phase Ib trial of cabozantinib in combination with Roche’s (OTC:RHHBY) Tecentriq. The drug will be evaluated in patients suffering from locally advanced or metastatic urothelial carcinoma (UC) or renal cell carcinoma (RCC).

The primary endpoint of the study is to determine the optimal dose and schedule of daily oral administration of cabozantinib when given in combination with Tecentriq for the subsequent expansion stage.

The FDA granted accelerated approval to immuno-oncology drug, Tecentriq in May 2016 for treating locally advanced or metastatic urothelial carcinoma. Initial uptake of the drug has been encouraging. In Oct 2016, Tecentriq became the first and only anti-PDL1 cancer immunotherapy to be approved by the FDA for the treatment of metastatic NSCLC.

The phase Ib open-label study is divided in two parts: a dose-escalation phase and an expansion cohort phase. The dose-escalation phase will enroll nine to 36 patients with inoperable, locally advanced, metastatic or recurrent UC (including renal, pelvis, ureter, urinary bladder and urethra) after prior platinum-based therapy or RCC with or without prior systemic therapy.

The starting dose of cabozantinib will be 40 mg daily which can be increased to 60 mg daily or decreased to 20 mg daily. The patients enrolled will receive the standard Tecentriq dosing regimen (1200 mg infusion once every 3 weeks).

The secondary end points of the dose-escalation stage are to evaluate the plasma pharmacokinetics of daily oral administration of cabozantinib when given in combination with Tecentriq and to assess safety of the combination therapy through the evaluation of incidence and severity of adverse events, including immune-related adverse events.

Upon determination of the recommended dose and schedule, 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 UC or RCC.

Exelixis is developing cabozantinib in a broad development program comprising over 45 clinical studies across multiple indications. The company received a significant boost in Apr 2016 when the FDA approved the tablet formulation of cabozantinib, (distinct from the capsule form) under the brand name Cabometyx for the treatment of RCC in patients who have received prior anti-angiogenic therapy.

Cabometyx was also approved in EU in Sep 2016 for the treatment of advanced RCC in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy.