A Phase 1 trial assessing the combination of Exelixis‘ Cabometyx (cabozantinib) and Genentech‘s Tecentriq (atezolizumab) in locally advanced or metastatic urothelial carcinoma (UC) or renal cell carcinoma (RCC) is set to get underway.
“Patients with locally advanced or metastatic urothelial or renal cell carcinoma are in need of additional therapies that can slow disease progression,” Sumanta Kumar Pal, MD, principal investigator of the study, said in a press release. Pal is co-director of the Kidney Cancer Program at City of Hope in California.
The ongoing Phase 1 trial (NCT03170960) is a multicenter, open-label study designed to evaluate the safety, tolerability, preliminary effectiveness, and pharmacokinetics (PK) of Cabometyx in combination with Tecentriq in UC and RCC patients. UC patients included those with cancers of the bladder, renal pelvis, ureter, or urethra.
The study will be conducted in two stages: A dose escalation stage and an expansion stage. In the dose-escalation stage, patients will receive increasing doses of Cabometyx plus the standard Tecentriq dose, to establish the recommended Cabometyx dose. Each dose group will include three to six participants with locally advanced, metastatic or recurrent UC who have already undergone platinum-based therapy, or RCC with or without prior systemic therapy.
The secondary objectives of this stage of the study will be evaluations of incidence and severity of non-serious adverse events (AEs) and serious adverse events (SAEs), including immune-related adverse events (irAEs) for the combination therapy.
In the expansion stage, four tumor-specific groups will be enrolled:
- patients who have progressed on or after platinum-based chemotherapy;
- patients who are ineligible for Platinol (cisplatin)-based chemotherapy and who have not received prior systemic chemotherapy for inoperable, locally advanced or metastatic disease;
- patients who are eligible for Platinol-based chemotherapy and have not received prior systemic chemotherapy for inoperable, locally advanced or metastatic disease, and;
- patients with clear cell histology who have not received prior systemic anticancer therapy for RCC.
Each group will enroll up to 30 patients, for a total of up to 120 people, to further evaluate the safety and effectiveness of the combination therapy in these tumor conditions.
“There is a strong rationale for combining cabozantinib with immunotherapies, including clinical and preclinical observations consistent with the ability of cabozantinib to promote an immuno-permissive environment, which might present an opportunity for synergistic effects from combination treatment with immune checkpoint inhibitors and other immuno-oncology agents,” said Gisela Schwab, MD, president, Product Development and Medical Affairs and chief medical officer at Exelixis. “We are excited to evaluate the combination of cabozantinib plus atezolizumab and look forward to the determination of a recommended phase 2 dose and to further examining this combination regimen to treat advanced cancers.”
Cabometyx is a multi-kinase inhibitor that inhibits RET and the MET, AXL, and VEGF receptors, all involved in tumor development, metastasis, blood vessel growth, drug resistance, and maintenance of the tumor microenvironment.
Cabometyx tablets were approved by both the U.S. Food and Drug Administration and the European Commission in 2016 for the treatment of patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.
