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– Data from three cohorts of phase 1b COSMIC-021 trial to be presented during the 2020
– 27% objective response rate seen in immune checkpoint inhibitor-pretreated non-small cell lung cancer cohort 7 –
– Phase 3 pivotal trials planned for advanced non-small cell lung cancer and metastatic castration-resistant prostate cancer –
NSCLC Expansion Cohort (abstract 9610):
Initial results from the NSCLC expansion cohort (cohort 7) will be presented by
At a median follow-up of 12.1 months, the investigator-assessed confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1, the trial’s primary endpoint, was 27%, and the disease control rate was 83%. Median progression-free survival (PFS) was 4.2 months (95% confidence interval [CI] 2.7–7 months) with 22 events (73%), and median duration of response for all responding patients was 5.7 months.
“Cabozantinib, in combination with immune checkpoint inhibitors, has now demonstrated promise in multiple difficult to treat tumor types,” said Dr.
The most common treatment-related adverse events (AEs) were diarrhea (53%), fatigue (37%), nausea (30%), decreased appetite (23%), palmar-plantar erythrodysesthesia (20%) and vomiting (20%). One patient experienced grade 5 pneumonitis that was related to atezolizumab, and one patient (3%) discontinued due to treatment-related AEs not associated with disease progression.
“We are encouraged by these promising findings in patients with non-small cell lung cancer who had been previously treated with immune checkpoint inhibitor therapy, along with other COSMIC-021 results presented at ASCO20,” said
UC Expansion Cohort (abstract 5013):
Initial results from the UC expansion cohort (cohort 2) will be presented by
The most common treatment-related AEs were asthenia (37%), diarrhea (27%), decreased appetite (23%), increased transaminases (23%) and mucosal inflammation (20%). No discontinuations due to treatment-related AEs occurred.
CRPC Expansion Cohort (abstract 5564):
An interim analysis from the metastatic CRPC expansion cohort (cohort 6) was previously presented at the 2020 American Society of Clinical Oncology’s Genitourinary Cancers Symposium and was now updated with additional biomarker results that will be presented by
Additional safety and efficacy findings from this analysis were previously presented at the 2020 American Society of Clinical Oncology’s Genitourinary Cancers Symposium.
Based on regulatory feedback from the
More information about COSMIC-021 is available at ClinicalTrials.gov (NCT03170960).
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 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, 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.
Lung cancer is the second most common type of cancer in the
Urothelial cancers encompass carcinomas of the bladder, ureter and renal pelvis at a ratio of 50:3:1, respectively.4 Bladder cancer occurs mainly in older people, with 90 percent of patients aged 55 or older.5 With more than 81,000 new cases expected to be diagnosed in 2020, bladder cancer accounts for about five percent of all new cases of cancer in the
According to the
About CABOMETYX® (cabozantinib)
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 NSCLC, metastatic CRPC and UC cohorts of the COSMIC-021 trial will be presented at ASCO20; the potential synergistic effects with cabozantinib and immune checkpoint inhibitors; Exelixis’ plans to initiate phase 3 pivotal trials in advanced or metastatic NSCLC and CRPC; Exelixis’ intention to file with the FDA for accelerated approval of the combination of cabozantinib and atezolizumab in a metastatic CRPC indication as early as 2021, based on regulatory feedback from the FDA and if supported by the clinical data; and Exelixis’ plans to reinvest in its business to maximize the potential of the company’s pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the continuing COVID-19 pandemic and its impact on Exelixis’ research and development operations, including Exelixis’ ability to initiate new clinical trials and clinical trial sites, enroll clinical trial patients, conduct trials per protocol, and conduct drug research and discovery operations and related activities; the availability of data at the referenced times; complexities and the unpredictability of the regulatory review and approval processes in the
TECENTRIQ® (atezolizumab) is a registered trademark of
4 Hurwitz, M. et al. Urothelial and Kidney Cancers. Cancer Management. http://www.cancernetwork.com/cancer-management/urothelial-and-kidney-cancers. Accessed
9 Scher, H.I., Solo, K., Valant, J., Todd, M.B., Mehra, M. Prevalence of Prostate Cancer Clinical States and Mortality in
11 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.
EVP, Public Affairs and
Senior Director, Public Affairs and Advocacy Relations