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Data from the COSMIC-021 trial will be presented on
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 (
“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
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%.
“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
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
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.
According to the
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
Important Safety Information
Warnings and Precautions
Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. 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: Gastrointestinal (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 Grade 4 fistula 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 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.
Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings 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.
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.
USE IN SPECIFIC POPULATIONS
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’ expectation that data from the CRPC cohort of the COSMIC-021 trial will be presented at ASCO GU 2020; the therapeutic potential of cabozantinib in combination with atezolizumab for patients with CRPC and other difficult-to-treat tumor types; Exelixis’ intention to file with the
TECENTRIQ® (atezolizumab) is a registered trademark of Genentech, a member of the
3 Scher, H.I., Solo, K., Valant, J., Todd, M.B., Mehra, M. Prevalence of Prostate Cancer Clinical States and Mortality in
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.
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EVP, Public Affairs and
Senior Director, Public Affairs and Advocacy Relations