Combining cabozantinib with either Opdivo (nivolumab) or Opdivo plus Yervoy (ipilimumab) shows promise as a treatment for refractory metastatic urothelial carcinoma (mUC) and other genitourinary tumors, according to results of a Phase 1 trial.
The results, which covered patients whose genitourinary tumors had spread to other parts of the body, were presented Feb. 17 at the 2017 Genitourinary Cancers Symposium in Orlando, Florida. Genitourinary tumors occur in the genital or urinary organs — the urinary tract, bladder, kidneys, ureter, prostate, testicles, penis or adrenal glands.
The open-label, multicenter trial (NCT02496208) was designed to assess the safety and effectiveness of Exelixis’s renal cell carcinoma drug cabozantinib, marketed as Cabometyx, in combination with either Opdivo alone or Opdivo plus Yervoy.
Nineteen of the 48 patients with refractory and metastatic urothelial carcinoma had mUC. The trial also covered urachal adenocarcinoma, squamous cell carcinoma of the bladder or urethra, germ cell tumor, castration-resistant prostate cancer, renal cell carcinoma, trophoblastic tumor, sertoli cell tumor, and penile squamous cell carcinoma.
Patients were enrolled between July 22, 2015, and December 31, 2016.
The U.S. National Cancer Institute (NCI), a division of the National Institutes of Health, paid for the trial through Cooperative Research and Development Agreements.
It was conducted in two parts to determine dose levels that patients could tolerate. In part 1, 30 patients received cabozantinib plus Opdivo at four dose levels. In part 2, 18 patients received cabozantinib plus Opdivo and Yervoy in three dose levels.
Thirty percent of the 43 patients achieved an objective response to the combo therapy — defined as either a full or partial response. They included 38 percent who responded to the Part 1 treatment and 1 percent who responded to the Part 2 therapy.
Seven percent of the patients achieved a complete response and 23 percent a partial response. In addition, 56 percent of patients achieved a stable-disease situation. The results translated to a disease control rate of 86 percent.
Patients with mUC had an overall response rate of 38 percent, including two complete responses, and a disease control rate of 94 percent. Two patients with squamous cell carcinoma of the bladder achieved objective responses.
“There is a significant unmet need for treatment regimens that can slow tumor progression in advanced, intractable cancers such as metastatic urothelial carcinoma. The use of combination therapies may be a strategy that could increase anti-tumor activity in these patients,” Andrea Apolo, MD, the trial’s principal investigator, said in a news release.
“Previously reported data from Part I of the trial showed that cabozantinib in combination with nivolumab provided an encouraging objective response rate and tolerability profile across a diverse range of genitourinary tumors,” added Apolo, who is with the NCI’s Genitourinary Malignancies Branch. “Data from Part II also demonstrate that using cabozantinib with two immunotherapy agents is well-tolerated, with promising early activity. These results support the further evaluation of both regimens in these tumor types.”
The most common grade 3 adverse events in part 1 included low number of the immune cells known as neuthrophils, low phosphate levels, high blood pressure, fatigue, diarrhea and dehydration. In part 2, grade 3 adverse events included high blood pressure, low phosphate and sodium levels, fatigue, nausea and rash.
“These early clinical results generated by our collaborators at the NCI-Cancer Therapy Evaluation Program suggest that the combination of cabozantinib with either nivolumab or nivolumab and ipilimumab in patients with genitourinary malignancies is associated with an encouraging tolerability, safety and activity profile,” said Michael M. Morrissey, PhD, president and CEO of Exelixis. “With these results in hand, we are committed to further examining the potential of cabozantinib in combination with a variety of immunotherapies to treat a broad range of genitourinary and other cancers.”