In 2014, Exelixis’ Cabometyx (cabozantinib) failed to show survival benefit as a monotherapy in prostate cancer.
In 2014, Exelixis’ Cabometyx (cabozantinib) failed to show survival benefit as a monotherapy in prostate cancer. That disappointment caused the company to cut 70% of its workforce and focus on other products in its pipeline. Now, the company and cabozantinib appear to be bouncing back, with promising Phase I results in prostate cancer with cabozantinib in combination with Genentech’s checkpoint inhibitor Tecentriq (atezolizumab).
Exelixis announced positive results from the metastatic castration-resistant prostate cancer (CRPC) cohort of COSMIC-021, the Phase Ib trial of Cabometyx and Tecentriq in patients with locally advanced or metastatic solid tumors. The company plans to present the data Thursday, February 13 at the 2020 American Society of Clinical Oncology’s Genitourinary Cancers Symposium in San Francisco.
At the time of enrollment, patients were required to have measurable disease per Response Evaluation Criteria in Solid Tumors and their disease had progressed on previous novel hormone therapy. They may have received previous docetaxel for hormone sensitive disease.
The interim analysis included 44 patients with a median follow-up of 12.6 months. The objective response rate (ORR), the trial’s primary endpoint, was 32%, including two complete responses and 12 partial responses. The disease control rate came in at 80%. In 36 patients with high-risk clinical features that included visceral metastases and/or extra-pelvic lymph node metastases, the ORR was 33%.
The median duration of response for all patients that responded was 8.3 months. Of the 12 patients who had an objective response and at least one post-baseline prostate-specific antigen (PSA) evaluation, 67% showed their PSA dropped at least 50%.
“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,” said Neeraj Agarwal, professor, Huntsman Cancer Center, University of Utah, and a trial investigator. “Emerging data suggests 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.”
On January 7, 2020, Exelixis expanded enrollment up to 130 patients in the metastatic CRPC cohort 6 of the trial. The U.S. Food and Drug Administration (FDA) provided feedback on the data so far, providing confidence for Exelis to file with the agency for accelerated approval in a metastatic CRPC indication as early as 2021.
“We’re happy to share these encouraging results from the metastatic CRPC cohort from COSMIC-021, our first trial evaluating the combination of cabozantinib and atezolizumab,” said Gisela Schwab, Exelixis’ president, Product Development and Medical Affairs, and chief medical officer. “We look forward to receiving data from the most recent expansion of this CRPC cohort while we are also preparing for the initiation of a Phase III pivotal trial in this indication. We are excited about the emerging data in metastatic CRPC and elsewhere and the potential of combining cabozantinib with immunotherapies in this and other difficult-to-treat tumor types.”
Cabometyx is approved in the U.S. for advanced renal cell carcinoma (RCC) and patients with hepatocellular carcinoma (HCC) who have previously been treated with sorafenib.
