Exelixis has launched a Phase 3 trial that will investigate the safety and efficacy of a combination therapy of Cabometyx (cabozantinib) and Tecentriq (atezolizumab) in people with advanced renal cell carcinoma (RCC) whose cancer progressed while being treated with an immune checkpoint inhibitor or shortly thereafter.
The pivotal study, called CONTACT-03 (NCT04338269), aims to enroll approximately 500 patients with inoperable, locally advanced, or metastatic RCC. Patient recruitment has started at the City of Hope Comprehensive Cancer Center in the U.S. and at the Severance Hospital in Korea, with more than 100 sites in the U.S., Europe, Asia, Australia, and Argentina expected to open soon.
During the study, which is being sponsored by Roche and co-funded by Exelixis, patients will be randomly assigned to receive either the Cabometyx-Tecentriq combination, or Cabometyx alone.
The main goal of the study is to determine if the combination therapy is superior to Cabometyx alone at prolonging the time patients live without disease progression, as well as their overall survival.
Secondary goals include assessing the percentage of patients responding to treatment, and the type and duration of responses attained.
“The treatment landscape for metastatic kidney cancer is rapidly evolving as the use of immune checkpoint inhibitor-based regimens move to earlier lines of therapy,” Gisela Schwab, MD, president of Product Development and Medical Affairs and chief medical officer at Exelixis, said in a press release.
“More data are needed to better understand the sequential use of treatments for this patient community, and we look forward to learning more about the potential role of the combination of cabozantinib and atezolizumab following checkpoint inhibitor therapy in this pivotal trial with our partner Roche,” she added.
Tecentriq, developed by Genentech, a member of the Roche group, belongs to a class of immunotherapies known as immune checkpoint inhibitors that work by blocking proteins used by cancer cells to evade immune responses. Tecentriq specifically blocks PD-L1, which is produced by cancer cells and dampens immune responses when bound to the PD-1 receptor on immune cells.
Cabometyx, developed by Exelixis, is a small molecule that blocks enzymes called tyrosine kinases, which are involved in several tumor processes, including the formation of new blood vessels, as well as tumor cell migration and invasiveness.
The therapy is approved for people with advanced kidney cancer, but evidence suggests that Cabometyx induces changes in tumors that make them more permissive to the entry of immune cells. This has led researchers to believe that Cabometyx may work well in combination with immune checkpoint inhibitors such as Tecentriq.
CONTACT-01, launched in early June, aims to assess the safety, efficacy, and pharmacological properties of the Cabometyx-Tecentriq combo therapy in patients with metastatic non-small cell lung cancer (NSCLC), whose disease progressed after treatment with an immune checkpoint inhibitor and platinum-based chemotherapy.
The study seeks to enroll about 350 patients and is recruiting participants at a site in New Mexico. Additional sites are expected to open soon in the U.S., Europe, Japan, and Korea.
During the study, patients will be randomly assigned to receive either the combination therapy or the chemotherapy docetaxel. The main goal is to determine if the Cabometyx-Tecentriq combo is better than docetaxel at prolonging patient survival.
CONTACT-02, launched in late June, was designed to assess the safety and efficacy of the Cabometyx-Tecentriq combo therapy in men with metastatic castration-resistant prostate cancer (mCRPC), who previously received treatment with a novel hormone therapy.
The trial is planning to enroll 580 men from 250 sites. Patient recruitment has started at two sites in the U.S.
During the study, men will be randomly assigned to receive either the Cabometyx-Tecentriq combination therapy or a second novel hormone therapy — either Zytiga (abiraterone) plus prednisone or Xtandi (enzalutamide). The main goal is to determine if the combination therapy is superior to hormone therapy at prolonging the time patients live without disease worsening, as well as their overall survival.
The design of all three Phase 3 trials was informed by the ongoing Phase 1b COSMIC-021 trial (NCT03170960), which assessed the safety, tolerability, pharmacological properties, and preliminary efficacy of the Cabometyx-Tecentriq combo therapy in patients with different types of solid cancers, including RCC, NSCLC, and mCRPC.
Interim data from the study, presented at the 2020 ASCO’s Genitourinary Cancers Symposium, showed that approximately a third (32%) of the 44 patients included in the analyses responded to treatment. A similar response rate (33%) was observed in a subgroup of 36 patients with high-risk clinical features, including extensive cancer spread. Responses lasted a median of 6.3 months.
An updated analysis of the study included data from three expansion cohorts of patients with NSCLC, mCRPC, and urothelial carcinoma, and showed that 27%–32% of patients in each cohort responded to the combo therapy. The analysis was presented at the 2020 ASCO Oncology Virtual Scientific Program.
COSMIC-021, which is still recruiting participants at several sites in the U.S. and Europe, is expected to conclude in December 2021.