Exelixis Announces Final Five-Year Follow-up Results from CheckMate -9ER Trial Evaluating CABOMETYX® (cabozantinib) in Combination with Opdivo® (nivolumab) in Patients with Advanced Kidney Cancer at ASCO GU 2025
– After more than five years of follow-up, CABOMETYX in combination with Opdivo continued to show survival benefit compared with sunitinib –
– Long-term efficacy seen across subgroups, including site of metastases –
“In this evolving treatment landscape for renal cell carcinoma, patients are looking for options that have shown improved survival time in the long-term,” said Robert J. Motzer, M.D., Kidney Cancer Section Head, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center. “These final five-year results from CheckMate -9ER demonstrated the durable clinical benefits of cabozantinib in combination with nivolumab—including for those with organ metastases or intermediate- or poor-risk disease classifications—and continue to support this combination regimen as a valuable first-line option for this patient population.”
At a median follow-up of 67.6 months, CABOMETYX in combination with Opdivo improved progression-free survival (PFS; hazard ratio [HR]: 0.58;
Table 1 |
CABOMETYX + Opdivo |
Sunitinib |
ITT population (n=651) |
||
Median PFS, mo |
16.4 |
8.3 |
PFS HR ( |
0.58 (0.49-0.70) |
|
Median OS, mo |
46.5 |
35.5 |
OS HR ( |
0.79 (0.65-0.96) |
|
ORR, % |
55.7 |
27.4 |
DOR, mo |
22.0 |
15.2 |
Favorable IMDC risk (n=146) |
||
Median PFS, mo |
21.4 |
12.8 |
PFS HR ( |
0.67 (0.46-0.97) |
|
Median OS, mo |
53.7 |
58.9 |
OS HR ( |
1.08 (0.70-1.66) |
|
ORR, % |
66.2 |
43.1 |
Intermediate/poor IMDC risk (n=505) |
||
Median PFS, mo |
15.4 |
7.1 |
PFS HR ( |
0.56 (0.46-0.69) |
|
Median OS, mo |
43.9 |
29.2 |
OS HR ( |
0.74 (0.60-0.92) |
|
ORR, % |
52.6 |
23.0 |
CI: confidence interval; DOR: duration of response; HR: hazard ratio; IMDC: International Metastatic RCC Database Consortium; ITT: intent-to-treat; ORR: objective response rate; OS: overall survival; PFS: progression-free survival |
In an analysis by baseline metastases sites, PFS, OS and ORR favored the combination regimen versus sunitinib in all three subgroups (liver, bone and lung). Detailed results are shown in Table 2.
Table 2 |
Liver |
Bone |
Lung |
|||
CABOMETYX
|
Sunitinib
|
CABOMETYX
|
Sunitinib
|
CABOMETYX
|
Sunitinib
|
|
Median PFS, mo |
10.9 |
6.2 |
13.8 |
5.3 |
16.4 |
8.3 |
PFS HR ( |
0.55 (0.37-0.82) |
0.43 (0.30-0.64) |
0.56 (0.46-0.69) |
|||
Median OS, mo |
37.6 |
22.1 |
34.8 |
20.7 |
47.5 |
32.4 |
OS HR ( |
0.65 (0.43-0.97) |
0.66 (0.45-0.95) |
0.75 (0.60-0.94) |
|||
ORR, % |
52.1 |
21.4 |
49.4 |
9.3 |
57.3 |
27.9 |
CI: confidence interval; HR: hazard ratio; IMDC: ORR: objective response rate; OS: overall survival; PFS: progression-free survival |
“With now more than five years of follow-up, these results continue to support CABOMETYX in combination with Opdivo as a treatment regimen that can have enduring survival benefits for patients with previously untreated advanced kidney cancer,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “The efficacy was sustained across multiple subgroups, further underscoring the potential of this regimen to benefit a broad population with variable disease burden. We are proud to have established such a compelling standard of care for this community and remain committed to developing much-needed treatment options for all patients living with advanced cancers.”
Safety and tolerability with long-term follow-up were manageable and consistent with previous analyses. No new safety signals were reported. Grade 3/4 adverse events (AEs) occurred in
About CheckMate -9ER
CheckMate -9ER is an open-label, randomized, multi-national phase 3 trial evaluating patients with previously untreated advanced or metastatic RCC. A total of 651 patients (
About RCC
Kidney cancer is among the top ten most commonly diagnosed forms of cancer among both men and women in the
About CABOMETYX® (cabozantinib)
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
Perforations and Fistulas: Fistulas, including fatal cases, occurred in
Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in
Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in
Diarrhea: Diarrhea occurred in
Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in
Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.
Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.
With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in
Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.
Adrenal insufficiency occurred in
Approximately
Proteinuria: Proteinuria was observed in
Osteonecrosis of the Jaw (ONJ): ONJ occurred in <
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. 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.
Thyroid Dysfunction: Thyroid dysfunction, primarily hypothyroidism, has been observed with CABOMETYX. Based on the safety population, thyroid dysfunction occurred in
Patients should be assessed for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitored for signs and symptoms of thyroid dysfunction during CABOMETYX treatment. Thyroid function testing and management of dysfunction should be performed as clinically indicated.
Hypocalcemia: CABOMETYX can cause hypocalcemia. Based on the safety population, hypocalcemia occurred in
In COSMIC-311, hypocalcemia occurred in
Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.
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 common (≥
CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.
CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.
DRUG INTERACTIONS
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.
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. Avoid CABOMETYX in patients with severe hepatic impairment.
Please see accompanying full Prescribing Information https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.
About Exelixis
Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com, follow @ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements, including, without limitation, statements related to: the presentation of final results from the CheckMate -9ER trial at ASCO GU 2025; the therapeutic potential of cabozantinib in combination with nivolumab and Exelixis’ belief that the regimen may provide enduring survival benefits for patients with previously untreated advanced kidney cancer; Exelixis’ belief in the ability of the regimen to benefit a broad population with variable disease burden; Exelixis’ commitment to developing much-needed treatment options for all patients living with advanced cancers; and Exelixis’ scientific pursuit to create transformational treatments that give more patients hope for the future. 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 availability of data at the referenced times; complexities and the unpredictability of the regulatory review and approval processes in the
Exelixis, the Exelixis logo and CABOMETYX are registered
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1 Cancer Facts & Figures 2025. ACS. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2025/2025-cancer-facts-and-figures-acs.pdf. Accessed February 2025.
2 Survival Rates for Kidney Cancer. ACS. Available at: https://www.cancer.org/cancer/types/kidney-cancer/detection-diagnosis-staging/survival-rates.html. Accessed February 2025.
3 Citeline’s Datamonitor Healthcare: Renal Cell Carcinoma. March 2023 (internal data on file).
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