Exelixis Announces Encouraging Results for Cabozantinib in Combination With Atezolizumab in Metastatic Castration-Resistant Prostate Cancer

Data from the COSMIC-021 trial will be presented on Thursday, February 13, 2020 at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium

ALAMEDA, CA, USA I February 10, 2020 IExelixis, Inc. (NASDAQ:EXEL) today announced encouraging results from the metastatic castration-resistant prostate cancer (CRPC) cohort of COSMIC-021, the phase 1b trial of cabozantinib (CABOMETYX®) in combination with atezolizumab (TECENTRIQ®) in patients with locally advanced or metastatic solid tumors. The data will be presented on Thursday, February 13th during Poster Session A: Prostate Cancer at 11:30 a.m. – 1:00 p.m. PT and 5:30 – 6:30 p.m. PT at the 2020 American Society of Clinical Oncology’s Genitourinary Cancers Symposium (ASCO GU 2020), which is being held in San Francisco, California, February 13 – 15, 2020.

Upon enrollment, patients had to have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1) and had progressed on prior novel hormone therapy and could have received prior docetaxel for hormone sensitive disease. Forty-four patients were included in this interim analysis. The median follow up was 12.6 months. The objective response rate (ORR) per RECIST v. 1.1, the trial’s primary endpoint, was 32%, including two complete responses and 12 partial responses. Disease control rate was 80%. Among the 36 patients with high-risk clinical features including visceral metastases and/or extra-pelvic lymph node metastases, the ORR was 33%. Median duration of response for all responding patients was 8.3 months. Among 12 patients who had an objective response and at least one post-baseline prostate-specific antigen (PSA) evaluation, 67% had a PSA decline of 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, M.D., Professor, Huntsman Cancer Center, University of Utah, and an investigator of the trial. “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.”

The median treatment duration was 6.3 months (range 1 to 18 months). No new safety signals were identified in this combination cohort. Treatment-related grade 3/4 adverse events (AEs) occurring in ≥5% of patients were fatigue (7%), diarrhea (7%) and hyponatremia (7%). One treatment-related grade 5 AE of dehydration was reported in a 90-year-old patient. The discontinuation rate of study treatment for adverse events unrelated to disease progression was low at 7%.

Exelixis announced on January 7, 2020 that metastatic CRPC cohort 6 of COSMIC-021 had been expanded to enroll up to 130 patients. Based on regulatory feedback from the U.S. Food & Drug Administration (FDA), and if supported by the clinical data from the recently expanded existing cohort and added metastatic CRPC cohorts, Exelixis intends to file with the FDA 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, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “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 3 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.”

More information about this trial is available at ClinicalTrials.gov.

About the COSMIC-021 Study

COSMIC-021 is a multicenter, phase 1b, open-label study that is divided into two parts: a dose-escalation phase and an expansion cohort phase. The dose-escalation phase was designed to enroll patients either with advanced renal cell carcinoma (RCC) with or without prior systemic therapy or with inoperable, locally advanced, metastatic or recurrent urothelial carcinoma (UC), (including renal, pelvis, ureter, urinary bladder and urethra) after prior platinum-based therapy. Ultimately, all 12 patients enrolled in this stage of the trial were patients with advanced RCC. The dose-escalation phase of the study determined the optimal dose of cabozantinib to be 40 mg daily when given in combination with atezolizumab (1200 mg infusion once every 3 weeks). These results were presented at the European Society for Medical Oncology 2018 Congress.

In the expansion phase, the trial is enrolling 24 cohorts in 12 tumor types: RCC, UC, non-small cell lung cancer (NSCLC), CRPC, hepatocellular carcinoma (HCC), triple-negative breast cancer, epithelial ovarian cancer, endometrial cancer, gastric or gastroesophageal junction adenocarcinoma, colorectal adenocarcinoma, head and neck cancer, and differentiated thyroid cancer. Up to 1,720 patients may enroll in this phase of the trial: each expansion cohort will initially enroll approximately 30 patients, and up to 10 cohorts may further expand enrollment resulting in up to 1,000 patients across such potential additional expansion cohorts.

Four of the cohorts are exploratory: three are enrolling approximately 30 patients each with advanced UC, CRPC or NSCLC to be treated with cabozantinib as a single-agent, and one is enrolling approximately 10 patients with advanced CRPC to be treated with single-agent atezolizumab. Exploratory cohorts have the option to be expanded up to 80 patients (cabozantinib) and 30 patients (atezolizumab) total.

Exelixis is the study sponsor of COSMIC-021. Ipsen has opted in to participate in the trial and is contributing to the funding for this study under the terms of the companies’ collaboration agreement. Roche is providing atezolizumab for the trial.

About CRPC

According to the American Cancer Society, approximately 192,000 new cases of prostate cancer will be diagnosed and 33,000 people will die from the disease this year.1 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 metastatic CRPC.2 Researchers estimate that in 2020, 43,000 people with prostate cancer will progress to metastatic CRPC, which has a median survival of less than two years.3,4,5

About CABOMETYX® (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with HCC who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan.

About Exelixis

Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery — all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor’s (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

1 American Cancer Society. Key Statistics for Prostate Cancer. Available at: https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Accessed February 2020.
2 American Society of Clinical Oncology. Cancer.Net. Treatment of Metastatic Castration-Resistant Prostate Cancer. September 8, 2014. Available at: https://www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer. Accessed February 2020.
3 Scher, H.I., Solo, K., Valant, J., Todd, M.B., Mehra, M. Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model. PLOS ONE. 2015; 10: e0139440.
4 American Urological Association. Prostate Cancer: Castration Resistant Guideline. 2018. Available at: https://www.auanet.org/guidelines/prostate-cancer-castration-resistant-guideline. Accessed February 2020.
5 Moreira, D. M., Howard, L. E., Sourbeer, K. N., et al. Predicting Time From Metastasis to Overall Survival in Castration-Resistant Prostate Cancer: Results From SEARCH. Clin Genitourin Cancer. 2017; 15: 60–66.e2.

SOURCE: Exelixis

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