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– Ten new trial cohorts added to expansion phase of combination trial, bringing the total number of cohorts to 18 –
The 10 new expansion cohorts will evaluate the combination of cabozantinib and atezolizumab in patients with:
- non-small cell lung cancer (NSCLC) with an EGFR mutation who have progressed following treatment with an EGFR-targeting tyrosine kinase inhibitor for metastatic disease
- renal cell carcinoma (RCC) with non-clear cell histology who have not had prior systemic anticancer therapy for inoperable, locally advanced, recurrent or metastatic disease
- triple-negative breast cancer who have progressed following treatment with at least one prior systemic therapy for inoperable, locally advanced, recurrent or metastatic disease
- epithelial ovarian cancer who have platinum-resistant or refractory disease
- endometrial cancer who have progressed following treatment with at least one prior systemic therapy for inoperable, locally advanced, recurrent or metastatic disease
- advanced hepatocellular carcinoma (HCC) who have a Child-Pugh score of A and have not had prior systemic anticancer therapy for inoperable, locally advanced, recurrent or metastatic disease
- gastric or gastroesophageal junction adenocarcinoma who have progressed following treatment with platinum-containing or fluoropyrimidine-containing chemotherapy for inoperable locally advanced, recurrent or metastatic disease
- colorectal adenocarcinoma who have progressed following treatment with systemic chemotherapy that contained fluoropyrimidine in combination with oxaliplatin or irinotecan for metastatic disease
- head and neck cancer of squamous cell histology who have progressed following treatment with platinum-containing chemotherapy for inoperable locally advanced, recurrent or metastatic disease
- differentiated thyroid cancer who are radio-refractory or deemed ineligible for treatment with iodine-131
“We look forward to expanding this phase 1b COSMIC-021 clinical trial of
cabozantinib in combination with atezolizumab in a number of additional
tumor types, which include patient populations in significant need of
new therapies that may improve response rates, slow disease progression
and improve treatment outcomes,” said
- RCC with clear cell histology who have not had prior systemic anticancer therapy
- urothelial carcinoma (UC) who have progressed on or after platinum-containing chemotherapy
- UC who are ineligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy for inoperable, locally advanced or metastatic disease
- UC who are eligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy for inoperable, locally advanced or metastatic disease
- advanced non-squamous NSCLC without a defined tumor genetic alteration (EGFR, ALK, ROS1, or BRAF) who have not received prior therapy with an immune checkpoint inhibitor
- NSCLC without a defined tumor genetic alteration who have progressed following treatment with an immune checkpoint inhibitor
- UC who have progressed following treatment with an immune checkpoint inhibitor
- castration-resistant prostate cancer (CRPC) who have previously received enzalutamide and/or abiraterone acetate and experienced radiographic disease progression in soft tissue
The dose-escalation phase of the study determined the optimal dose of cabozantinib as 40 mg daily when given in combination with atezolizumab (1200 mg infusion once every 3 weeks). Each expansion cohort of this multicenter phase 1b, open-label study will initially enroll approximately 30 patients. Up to 80 may enroll in the cohorts of patients with UC or NSCLC who have been previously treated with an immune checkpoint inhibitor, with up to a total of 640 patients in the entire study.
More information about the currently enrolling cohorts in this trial is available at ClinicalTrials.gov.
TECENTRIQ® (atezolizumab) is a registered trademark of
Genentech, a member of the
About Exelixis’ Collaboration with
About Exelixis’ Collaboration with Takeda
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in
U.S. Important Safety Information
- Hemorrhage: Severe and fatal hemorrhages have occurred with CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic events was 3% in CABOMETYX-treated patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
- Gastrointestinal (GI) Perforations and Fistulas: In RCC studies, fistulas were reported in 1% of CABOMETYX-treated patients. Fatal perforations occurred in patients treated with CABOMETYX. In RCC studies, gastrointestinal (GI) perforations were reported in 1% of CABOMETYX-treated patients. Monitor patients for symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula which cannot be appropriately managed or a GI perforation.
- Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. In RCC studies, venous thromboembolism occurred in 9% (including 5% pulmonary embolism) and arterial thromboembolism occurred in 1% of CABOMETYX-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
- Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension, including hypertensive crisis. In RCC studies, hypertension was reported in 44% (18% Grade ≥ 3) of CABOMETYX-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.
- Diarrhea: In RCC studies, diarrhea occurred in 74% of patients treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose.
- Palmar-Plantar Erythrodysesthesia (PPE): In RCC studies, palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume CABOMETYX at a reduced dose.
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
- Embryo-fetal Toxicity may be associated with CABOMETYX. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during CABOMETYX treatment and for 4 months after the last dose.
- Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, hypertension, PPE, weight decreased, vomiting, dysgeusia, and stomatitis.
- Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
- Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
- Lactation: Advise women not to breastfeed while taking CABOMETYX and for 4 months after the final dose.
- Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.
Founded in 1994,
Exelixis Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: the clinical and therapeutic
potential of cabozantinib in combination with atezolizumab in patients
with locally advanced or metastatic solid tumors; the potential for
COSMIC-021 to generate data that will inform late stage trials of
cabozantinib in combination with immune checkpoint inhibitors; the
potential for Ipsen’s and Takeda’s participation in future cabozantinib
studies under their respective collaborations and to have access to the
results to support potential future regulatory submissions in their
territories; Exelixis’ commitment to reinvesting in its business to
maximize the potential of its pipeline, including supplementing its
existing therapeutic assets through targeted business development
activities and internal drug discovery; and Exelixis’ mission to deliver
the next generation of Exelixis medicines and help patients recover
stronger and live longer. Words such as “look forward,” “may,” “will,”
“commitment,” “potential,” “intend,” or other similar expressions
identify forward-looking statements, but the absence of these words does
not necessarily mean that a statement is not forward-looking. In
addition, any statements that refer to expectations, projections or
other characterizations of future events or circumstances are
forward-looking statements. These forward-looking statements 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: Exelixis’ ability and the ability of its collaborators to
conduct clinical trials of cabozantinib and cobimetinib both alone and
in combination with other therapies sufficient to achieve a positive
completion; risks related to the potential failure of cabozantinib and
cobimetinib both alone and in combination with other therapies, to
demonstrate safety and efficacy in clinical testing; risks and
uncertainties related to regulatory review and approval processes and
Exelixis’ compliance with applicable legal and regulatory requirements;
the level of costs associated with Exelixis’ commercialization, research
and development and other activities; competition in the area of
business development activities and the inherent uncertainty of the drug
discovery process; Exelixis’ dependence on its relationships with its
cabozantinib collaboration partners, including, the level of their
investment in the resources necessary to successfully commercialize
partnered products in the territories where they are approved; market
acceptance of CABOMETYX, COMETRIQ, and COTELLIC and the availability of
coverage and reimbursement for these products; Exelixis’ dependence on
third-party vendors for the development, manufacture and supply of its
products; Exelixis’ ability to protect the company’s intellectual
property rights; market competition, including the potential for
competitors to obtain approval for generic versions of Exelixis’
marketed products; changes in economic and business conditions, and
other factors discussed under the caption “Risk Factors” in Exelixis’
quarterly report on Form 10-Q filed with the Securities and Exchange
Susan Hubbard, 650-837-8194
EVP, Public Affairs and Investor Relations
Lindsay Treadway, 650-837-7522
Senior Director, Public Affairs and Advocacy Relations