Cabozantinib/atezolizumab phase 3 combo trial launched in renal cell carcinoma

The phase 3 CONTACT-03 trial is exploring the combination of the multikinase inhibitor and immunotherapy agent in patients with renal cell carcinoma after exposure to an immune-checkpoint inhibitor.

The pivotal phase 3 CONTACT-03 trial has been launched with the goal of exploring the combination of the multikinase inhibitor cabozantinib (Cabometyx) with the PD-L1 inhibitor atezolizumab (Tecentriq) in patients with advanced renal cell carcinoma (RCC) and prior exposure to an immune-checkpoint inhibitor.1

CONTACT-03 is specifically accruing patients with inoperable, locally advanced or metastatic RCC after progression on an immune checkpoint inhibitor as the immediate prior therapy.

“The treatment landscape for metastatic kidney cancer is rapidly evolving as the use of immune checkpoint inhibitor–based regimens moves to earlier lines of therapy,” Gisela Schwab, MD, president, Product Development and Medical Affairs and chief medical officer, Exelixis, the manufacturer of cabozantinib, stated 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.”

The open-label, global, phase 3 CONTACT-03 trial (NCT04338269) is randomizing patients in a 1:1 ratio to cabozantinib alone or in combination with atezolizumab. The enrollment goal of the study is 500 patients. The coprimary study end points are overall survival and progression-free survival (PFS), with secondary end points including objective response rate and duration of response.

In the genitourinary cancer treatment paradigm, cabozantinib is currently approved by the FDA as a monotherapy for the treatment of patients with advanced RCC. Atezolizumab has several approved indications in urothelial carcinoma, but none yet in RCC.

Combination therapy with immune checkpoint inhibitors and tyrosine kinase inhibitors (TKIs) has been an area of intense focus in the RCC paradigm. For example, in April 2019, the FDA approved the PD-1 inhibitor pembrolizumab for use in combination with the TKI axitinib (Inlyta) for the first-line treatment of patients with advanced RCC.

The approval was supported by findings from the phase 3 KEYNOTE-426 trial,2 in which the combination led to a 47% (HR, 0.53; P <.0001) reduction in the risk of death versus sunitinib (Sutent) in patients with advanced RCC. The immunotherapy/TKI combination also significantly improved overall response and PFS compared with sunitinib alone.

Another immunotherapy/TKI regimen, avelumab plus axitinib, was approved by the FDA in May 2019 for the frontline treatment of patients with advanced RCC. The approval was based on findings from the phase 3 JAVELIN Renal 101 trial,3 which showed that the combination was associated with a 31% reduction in the risk of disease progression or death compared with sunitinib in patients with treatment-naïve, advanced RCC.


1. Exelixis Announces Initiation of CONTACT-03 Phase 3 Pivotal Trial of Cabozantinib in Combination With Atezolizumab in Previously Treated Metastatic Renal Cell Carcinoma. Published online July 20, 2020. Accessed July 20, 2020.

2. FDA Approves Merck’s KEYTRUDA (pembrolizumab) in Combination With Inlyta® (axitinib) as First-Line Treatment for Patients With Advanced Renal Cell Carcinoma (RCC). Merck. Published April 22, 2019. Accessed April 22, 2019.

3. FDA Approves Bavencio (Avelumab) Plus Inlyta (Axitinib) Combination for Patients With Advanced Renal Cell Carcinoma. Pfizer Oncology. Published May 14, 2019. Accessed May 14, 2019.