Pivotal Phase 3 Trial Initiated to Study Promising Cabozantinib/Atezolizumab Combo in Advanced RCC

July 22, 2020

A pivotal phase 3 trial has been initiated to explore the combination of cabozantinib and atezolizumab for the treatment of patients with inoperable, locally advanced or metastatic renal cell carcinoma who progressed during or after treatment with an immune checkpoint inhibitor immediately following initial therapy.

A pivotal phase 3 trial has been initiated to explore the combination of cabozantinib (Cabometyx) and atezolizumab (Tecentriq) for the treatment of patients with inoperable, locally advanced or metastatic renal cell carcinoma (RCC) who progressed during or after treatment with an immune checkpoint inhibitor immediately following initial therapy.1

The global CONTACT-03 study (NCT04338269) is part of a collaboration between the manufacturers of the 2 agents, Exelixis and Roche, to explore the combination in 3 different tumor types across 3 phase 3 clinical trials: one in patients with metastatic non–small cell lung cancer (NSCLC) who have been previously treated with an immune checkpoint inhibitor and platinum-containing chemotherapy (CONTACT-01) and another in patients with metastatic castration-resistant prostate cancer (mCRPC) who have been previously treated with a novel hormonal therapy (CONTACT-02).2,3

“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, Product Development and Medical Affairs, and chief medical officer, Exelixis, said in a statement. “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.”

Rationale for the CONTACT-03 trial came from the ongoing phase 1b COSMIC-021 trial (NCT03170960) with is exploring the use of the cabozantinib and atezolizumab combination in patients with various advanced solid tumors. The dose-escalation phase of the study included 12 patients with advanced RCC, and the expansion phase included 24 cohorts of 12 tumor types.

Initial findings from 3 of the cohorts (NSCLC, mCRPC, and urothelial carcinoma) were presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program showing high disease control rates in each of the 3 tumor types from 63% to 83%.

The design of the COSMIC-021 trial informed that of the CONTACT trials.

CONTACT-03 is a global, multicenter, randomized, open-label study that will randomize patients in a 1:1 fashion to receive either cabozantinib and atezolizumab or cabozantinib alone. The trial is looking to enroll approximately 500 patients with inoperable, locally advanced or metastatic RCC who had radiographic tumor progression on or after receiving checkpoint inhibition in the metastatic setting.

Eligible patients are those who have most recently received anti–PD-1/PD-L1 therapy of atezolizumab, avelumab (Bavencio), pembrolizumab (Keytruda), or nivolumab (Opdivo). Patients are also required to have a Karnofsky performance status of at least 70, adequate hematologic and end-organ function, negative hepatitis B and C virus.

In the experimental arm, patients will receive 1200 mg of intravenous atezolizumab at a fixed dose administered on day 1 of each 3-week cycle plus 60 mg of cabozantinib given orally once daily.

The coprimary end points are progression-free survival by independent review facility according to RECIST v1.1 criteria and overall survival. Secondary end points include investigator-assessed progression-free survival, objective response rate, duration of response, and safety.

References:

1. Exelixis Announces Initiation of CONTACT-03 Phase 3 Pivotal Trial of Cabozantinib in Combination With Atezolizumab in Previously Treated Metastatic Renal Cell Carcinoma. News release. Exelixis. July 20, 2020. Accessed July 22, 2020. https://bwnews.pr/3eOCvEz

2. Exelixis Announces Initiation of CONTACT-01 Phase 3 Pivotal Trial of Cabozantinib in Combination With Atezolizumab in Previously Treated Metastatic Non-small Cell Lung Cancer. News release. Exelixis. June 11, 2020. Accessed July 22, 2020. https://bit.ly/3ePrcfh

3. Exelixis Announces Initiation of CONTACT-02 Phase 3 Pivotal Trial of Cabozantinib in Combination With Atezolizumab in Previously Treated Metastatic Castration-Resistant Prostate Cancer. New release. Jun 30, 3030. Accessed July 22, 2020. https://bit.ly/2WLPBME