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– Based on continued encouraging efficacy and safety data, metastatic castration-resistant prostate cancer cohort further expanded to 130 patients –
– Initial data to be presented on
“We continue to see encouraging efficacy and safety data from the
prostate cancer cohort in COSMIC-021,” said
Based on preliminary encouraging activity, as determined by response assessment per Response Evaluation Criteria in Solid Tumors (version 1.1) (RECISTv1.1), and safety data of patients enrolled in the metastatic CRPC cohort, 50 additional patients with metastatic CRPC (130 total) who have histologically or cytologically confirmed adenocarcinoma of the prostate are being enrolled in the trial.
Initial data from the CRPC cohort in COSMIC-021 will be presented at
ASCO GU 2020 in
COSMIC-021 includes 24 cohorts and aims to enroll up to 1,732 patients with advanced or metastatic solid tumors including CRPC, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC), colorectal cancer, ovarian cancer, and urothelial carcinoma (UC), among others. The primary objective in the expansion stage of this trial is to determine the objective response rate in each cohort. More information about the currently enrolling cohorts in this trial is available at ClinicalTrials.gov. To date, early data from various cohorts of this study have informed the initiation or planned initiation of several phase 3 pivotal trials, evaluating the combination in advanced HCC, CRPC, NSCLC and RCC.
TECENTRIQ® (atezolizumab) is a registered trademark of
Genentech, a member of the
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 RCC with or without prior systemic therapy or with inoperable,
locally advanced, metastatic or recurrent 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
In the expansion phase, the trial is enrolling 24 cohorts in 12 tumor types: RCC, UC, NSCLC, CRPC, 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 expand enrollment up to 1,000 additional patients in the expansion phase.
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.
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
Please see Important Safety Information below and full U.S. prescribing information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
U.S. Important Safety Information
- Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.
- Perforations and Fistulas: GastrointestinaI (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.
- Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic event requiring medical intervention.
- Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension occurred in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.
- Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.
- Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.
- Proteinuria: Proteinuria occurred in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.
- Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 28 days prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution.
- Wound Complications: Wound complications were reported with CABOMETYX. Stop CABOMETYX at least 28 days prior to scheduled surgery. Resume CABOMETYX after surgery based on clinical judgment of adequate wound healing. Withhold CABOMETYX in patients with dehiscence or wound healing complications requiring medical intervention.
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
- Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.
- Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, and vomiting.
- Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.
Strong CYP3A4 Inducers: If coadministration with strong CYP3A4
inducers cannot be avoided, increase the CABOMETYX dosage.
Avoid St.John’s wort.
- Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.
- Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.
Please see accompanying full Prescribing Information https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
Founded in 1994,
This press release contains forward-looking statements, including,
without limitation, statements related to: Exelixis’ plans to further
expand the metastatic CRPC cohort of COSMIC-021 to include up to 130
patients and Exelixis’ belief that this expansion will allow
EVP, Public Affairs and
Senior Director, Public Affairs and Advocacy Relations