Exelixis will expand its Phase 1b clinical trial evaluating a combination of Cabometyx (cabozantinib) with Tecentriq (atezolizumab) to include more patients with metastatic castration-resistant prostate cancer (mCRPC), based on preliminary encouraging safety and effectiveness data.
“We continue to see encouraging efficacy and safety data from the prostate cancer cohort in COSMIC-021,” Gisela Schwab, MD, Exelixis’ president of product development and medical affairs, and chief medical officer, said in a press release.
“Expanding this cohort by an additional 50 patients will allow us to further document how the combination of cabozantinib and atezolizumab may benefit this patient population as we assess our potential regulatory plans for the combination and prepare to initiate a Phase 3 pivotal trial,” Schwab added.
With this decision, the group will now include up to 130 mCRPC patients in a trial that had already expanded from 30 to 80 patients in July 2019. More information on contacts and recruitment locations can be found here.
Initial data from this group of mCRPC patients will be presented on Feb. 13 at the 2020 American Society of Clinical Oncology’s Genitourinary Cancers Symposium, which will take place in San Francisco, California.
Exelixis’ Cabometyx works by suppressing the activity of specific enzymes called tyrosine kinases — which are abnormally activated or found in higher-than-normal levels in some types of cancers — and by promoting anti-tumor immune responses. It is approved for the treatment of certain types of kidney cancer, and liver cancer.
Tecentriq, developed by Genentech — a member of the Roche Group — is an immune checkpoint inhibitor designed to block PD-L1, a protein found in high levels on the surface of cancer cells as a mechanism to evade anti-tumor immune responses.
By preventing the interaction between PD-L1 and its PD-1 receptor in immune T-cells, Tecentriq boosts the ability of T-cells to detect and fight tumor cells. It is approved for the treatment of certain types of bladder cancer, lung cancer, and breast cancer.
Previous preclinical and clinical studies suggested that Cabometyx’s immune-related effects may facilitate the anti-cancer effects of immune checkpoint inhibitors such as Tecentriq.
The global, open-label, COSMIC-021 Phase 1b study (NCT03170960) is assessing the safety, tolerability, pharmacokinetics (uptake, distribution, and elimination in the body), and preliminary effectiveness of Cabometyx, in combination with Tecentriq, in people with advanced or metastatic solid tumors.
The study aims to enroll up to 1,732 patients with 12 types of solid tumors, including CRPC, and cancers of the kidney, liver, bladder, lung, and breast, among others.
The trial comprises a dose-escalation phase — designed to assess the optimal dose of Cabometyx in combination with a predefined dose of Tecentriq — and an expansion phase — in which patients receive the selected dose to continue studying its safety and efficacy.
The completed dose-escalation phase, which involved 12 people with advanced kidney cancer, determined that Cabometyx’s optimal dose was 40 mg per day, given in oral tablets. Tecentriq’s dose consists of 1,200 mg given intravenously (directly into the bloodstream) every three weeks.
The dose-escalation phase results were presented at the European Society for Medical Oncology 2018 Congress. Researchers also showed that 50% of patients in this initial group responded to the combination, including one who attained a complete response.
The expansion phase includes 24 groups of patients and aims to assess the proportion of patients responding to treatment in each group. These groups will initially include around 30 participants each, but recruitment may be expanded up to a total of 1,000 additional patients in 10 of these groups.
Four groups are considered exploratory, including one evaluating Cabometyx single therapy in 30 men with CRPC (which may be expanded to a total of 80 patients), and another testing Tecentriq single therapy in 10 advanced CRPC patients (which may be expanded to a total of 30 patients).
According to the company, initial data from several groups of patients in this trial, including the mCRPC group, have supported the launch or planned initiation of pivotal Phase 3 clinical trials evaluating the combination of Cabometyx with Tecentriq.