Cabozantinib Plus Atezolizumab Misses PFS End Point in Previously Treated Advanced RCC

Phase 3 CONTACT-03 trial | Image Credit: Nitiphol/ Adobe Stock Images

The combination of cabozantinib (Cabometyx) and atezolizumab (Tecentriq) did not significantly improve progression-free survival (PFS) over cabozantinib alone in patients with locally advanced or metastatic clear cell or non–clear cell renal cell carcinoma (RCC) who progressed during or following checkpoint inhibition, missing the primary end point of the phase 3 CONTACT-03 trial (NCT04338269).¹

Regarding safety, the profile of the regimen proved to be consistent with what is known about each individual agent. Notably, no new safety signals were observed with the doublet.

Detailed data from the trial will be shared at an upcoming medical conference, according to a press release issued by Exelixis, Inc.

To be eligible for enrollment to the multicenter, randomized, open-label, phase 3 CONTACT-03 trial, patients were required to have measurable disease by RECIST v1.1 criteria, a Karnofsky performance score of at least 70, and acceptable hematological and end organ function.² They also needed to have an archival tumor specimen available and a fresh biopsy if feasible.

Patients who received treatment with anticancer therapy within 28 days before study treatment was initiated were excluded, as were those who previously received cabozantinib or a mTOR inhibitor. Key exclusion criteria included having received more than 1 previous immune checkpoint inhibitor (ICI) regimen or ICI in the adjuvant setting and having previously received more than 2 lines of therapy in the advanced or metastatic setting. They also could not have symptomatic, untreated, or actively progressing central nervous system metastases or another significant intercurrent illness.

A total of 522 participants were randomly assigned 1:1 to receive intravenous atezolizumab at 1200 mg every 3 weeks plus oral cabozantinib at a daily dose of 60 mg or cabozantinib alone at the same dose. Treatment continued until loss of clinical benefit or intolerable toxicity. No crossover was permitted.

Randomization was stratified based on International Metastatic Renal Cell Carcinoma Database Consortium risk group (0 vs 1 to 2 vs ≥3), most recent ICI (frontline vs second line), and histology (dominant clear cell without sarcomatoid vs dominant non–clear cell without sarcomatoid vs any sarcomatoid component).

The primary efficacy end points included PFS by independent review facility (IRV) and RECIST v1.1 criteria and overall survival. Secondary end points comprised investigator (INV)-assessed PFS by RECIST v1.1 criteria, as well as IRF- and INV-assessed objective response rate and duration of response. Investigators are also evaluating safety, health-related quality of life, and biomarkers.

CONTACT-03 is sponsored by Roche and co-funded by Exelixis.¹

References

1. Exelixis provides update on phase 3 CONTACT-03 trial evaluating cabozantinib in combination with atezolizumab in patients with previously treated advanced kidney cancer. News release. Exelixis, Inc. March 2, 2023. Accessed March 6, 2023. https://ir.exelixis.com/news-releases/news-release-details
2. Pal SK, Albiges L, Rodriguez CS, et al. CONTACT-03: randomized, open-label phase III study of atezolizumab plus cabozantinib versus cabozantinib monotherapy following progression on/after immune checkpoint inhibitor (ICI) treatment in patients with advanced/metastatic renal cell carcinoma. J Clin Oncol. 2021;39(suppl 6):TPS370. doi:10.1200/JCO.2021.39.6_suppl.TPS370