ALAMEDA, Calif. – Exelixis, Inc. today announced detailed results from CONTACT-02, a phase 3 pivotal study evaluating cabozantinib (CABOMETYX®) in combination with atezolizumab compared with a second novel hormonal therapy (NHT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and measurable extra-pelvic soft tissue disease who have progressed on one prior NHT. The detailed findings were presented during Oral Abstract Session A: Prostate Cancer at the American Society of Clinical Oncology 2024 Genitourinary Cancers Symposium (ASCO GU).
“Patients with metastatic castration-resistant prostate cancer with prior progression on a novel hormone therapy and who have measurable soft tissue metastasis experience the worst outcomes among advanced prostate cancer patients and have limited treatment options,” said Neeraj Agarwal, M.D., FASCO, Senior Director for Clinical Research at Huntsman Cancer Institute at the University of Utah and the global lead investigator of the trial. “CONTACT-02 is the only phase 3 study evaluating a tyrosine kinase inhibitor and an immune checkpoint inhibitor to show a statistically significant improvement in progression-free survival and a trend for overall survival in these patients. I am encouraged by these results and the potential for cabozantinib plus atezolizumab to be a widely available treatment option for our patients.”
As announced in August 2023, CONTACT-02 met one of its primary endpoints, demonstrating a statistically significant improvement in progression-free survival (PFS) as assessed by a blinded independent radiology committee (BIRC) and per RECIST 1.1. The PFS analysis was conducted in the first 400 randomized patients in the intent-to-treat (PFS ITT) population and per protocol. Similar results were observed for all patients.
Detailed results presented at ASCO GU show that at a median follow-up of 14.3 months for the PFS ITT population, the hazard ratio (HR) was 0.65 (95% confidence interval [CI]: 0.50-0.84; p=0.0007); the median PFS (mPFS) was 6.3 months for cabozantinib in combination with atezolizumab compared with 4.2 months for second NHT. This was nearly identical to the PFS for the ITT population (n=507): HR was 0.64 (95% CI: 0.50-0.81, p=0.0002); mPFS was 6.3 months for cabozantinib in combination with atezolizumab and was 4.2 months for second NHT. At a median follow-up of 12.0 months for the ITT population, the median overall survival (OS) was 16.7 months for cabozantinib in combination with atezolizumab compared with 14.6 months for second NHT (HR: 0.79; 95% CI: 0.58-1.07; p=0.13). While a trend toward OS improvement was observed, the data were immature and did not meet the threshold for statistical significance. The study will continue to the next analysis of OS, anticipated in 2024.
Treatment-emergent adverse events (AEs) occurred in 97% of patients treated with cabozantinib in combination with atezolizumab (n=248) compared with 87% of patients treated with a second NHT (n=253), 48% and 23% of which were grade 3/4, respectively. Grade 5 treatment-emergent AEs occurred in 8% of patients treated with the combination regimen compared with 12% of patients treated with a second NHT; no grade 5 treatment-related AEs occurred in either arm. Treatment-related AEs led to the discontinuation of any treatment component in 13% of patients treated with the combination regimen and 2% of patients treated with a second NHT. For all treatment components, the treatment-related AEs leading to discontinuation were 5% vs. 2%, respectively.
“Given there are limited options after progression on novel hormonal therapy, we recognize the need for a regimen that can delay disease progression, that has an acceptable tolerability profile and that is widely available to patients who may not have the means or desire to travel to specialized centers for other therapies,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “Our decision to conduct CONTACT-02, based upon a signal we observed in COMET-01, underscores our commitment to patients with advanced prostate cancer and to improving their standard of care. We look forward to discussing these important results with the U.S. Food and Drug Administration, and to learning more in the next analysis of overall survival, anticipated this year.”
About CONTACT-02
CONTACT-02 is a global, multicenter, randomized, phase 3, open-label study that randomized 507 patients 1:1 to the experimental arm of cabozantinib in combination with atezolizumab and the control arm of a second NHT (either abiraterone and prednisone or enzalutamide). The two primary endpoints of the trial are PFS and OS. The study included patients with mCRPC who have measurable extra-pelvic soft tissue metastasis and who have progressed on one prior NHT. The secondary endpoint is objective response rate per BIRC. The trial is sponsored by Exelixis and co-funded by Ipsen, Roche and Takeda Pharmaceutical Company Limited (Takeda). Takeda is conducting the trial in Japan.
About CRPC
According to the American Cancer Society, approximately 299,000 new cases of prostate cancer will be diagnosed in the U.S., and over 35,000 people will die from the disease in 2024. Prostate cancer that has spread beyond the prostate and does not respond to androgen-suppression therapies – a common treatment for prostate cancer – is known as mCRPC. Men diagnosed with mCRPC often have a poor prognosis, with an estimated survival of 1-2 years.
About CABOMETYX® (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced renal cell carcinoma (RCC); for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; for patients with advanced RCC as a first-line treatment in combination with nivolumab; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen Pharma SAS exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.
CABOMETYX in combination with atezolizumab is not indicated as a treatment for mCRPC.
About Exelixis
Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future.
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