The combination of cabozantinib in combination with atezolizumab demonstrated encouraging efficacy and tolerability in patients with metastatic castration-resistant prostate cancer, according to the updated results of the phase Ib COSMIC-021 trial. The trial is evaluating the combination in locally advanced or metastatic solid tumors, Elexis, Inc, announced in a press release.
Neeraj Agarwal, MD
The combination of cabozantinib (Cabometyx) and atezolizumab (Tecentriq) demonstrated encouraging efficacy and tolerability in patients with metastatic castration-resistant prostate cancer (mCRPC), according to updated results of the phase Ib COSMIC-021 trial. The trial is evaluating the combination in locally advanced or metastatic solid tumors, Elexis, Inc, announced in a press release.
“Given the poor prognosis for men with metastatic castration-resistant prostate cancer, measurable visceral disease, and/or extra-pelvic lymph node metastases who have progressed on novel hormone therapies, we are excited to observe clinically meaningful activity with the combination of cabozantinib and atezolizumab in this COSMIC-021 cohort,” Neeraj Agarwal, MD, professor, Huntsman Cancer Center, University of Utah, and an investigator on the trial, said in a statement.
At a median follow-up of 12.6 months, the overall response rate (ORR) observed with the combination was 32%, which included 2 complete responses (CRs), and 12 partial responses (PRs). Cabozantinib plus atezolizumab also led to a disease control rate of 80%. In a subgroup of patients with high-risk clinical features including visceral metastases and/or extra-pelvic lymph node metastases, the ORR was 33%.
Overall, the median duration of response (DOR) observed was 8.3 months. Of the 12 patients who achieved an objective response, 67% had a prostate-specific antigen decline of at least 50% compared with their baseline measurements.
Treatment during the study lasted for a median of 6.3 months (range, 1-18 months). There were no new safety signals identified with the combination of cabozantinib plus atezolizumab. More than 5% of patients experienced grade 3/4 treatment-related adverse events (TRAEs), which were fatigue (7%), diarrhea (7%), and hyponatremia (7%). There was 1 grade 5 TRAE of dehydration. Few patients (7%) discontinued treatment due to the emergence of TRAEs.
“Emerging data suggest a tolerable safety profile and encouraging efficacy for this combination that may hold promise for these patients with limited treatment options, potentially providing patients with more time before the need for treatment with chemotherapy. We look forward to additional results as the trial progresses,” Agarwal stated.
COSMIC-021 is a 2-part multicenter, open-label study. The dose-escalation portion of the study was designed for patients either with advanced renal cell carcinoma (RCC) with or without prior systemic therapy or with those with inoperable, locally advanced, metastatic or recurrent urothelial carcinoma (UC), after prior platinum-based therapy. There were 12 patients enrolled in the dose-escalation study and the maximum tolerated dose for cabozantinib was determined to be 40 mg daily.
Investigators plan to enroll a total of up to 1720 patients to the dose-expansion portion of the study into 24 cohorts for several malignancies, including RCC, UC, nonsmall cell lung cancer, CRPC, hepatocellular carcinoma, triple-negative breast cancer, epithelial ovarian cancer, endometrial cancer, gastric or gastroesophageal junction adenocarcinoma, colorectal adenocarcinoma, head and neck cancer, and differentiated thyroid cancer. Initially, each cohort in the study will enroll 30 patients and later, 10 select cohorts may expand the number of participants by 1000. Four of these cohorts will be used for exploratory analysis and these cohorts may expand by a total of 80 participants.
The full results from the COSMIC-021 trial will be presented on February 13 during a poster session at the 2020 Genitourinary Cancers Symposium in San Francisco, California.
1. Exelixis Announces Encouraging Results for Cabozantinib in Combination With Atezolizumab in Metastatic Castration-Resistant Prostate Cancer [news release]. Alamedia, California: Exelixis, Inc; February 10, 2020. https://bit.ly/39svmaM. Accessed February 11, 2020.