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INDICATION

CABOMETYX^® (cabozantinib), in combination with nivolumab, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

In the primary analysis, CABOMETYX + OPDIVO^® (nivolumab) demonstrated superior efficacy vs sunitinib in 1L aRCC¹

Primary analysis in ITT population¹—Median follow-up time of 18.1 months; range: 10.6-30.6 months²

Median PFS doubled in the primary analysis¹*

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PFS results*: 16.6 months with CABOMETYX + OPDIVO (95% CI: 12.5-24.9; n=323) vs 8.3 months with sunitinib (95% CI: 7.0-9.7; n=328)¹

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49% reduction in risk of progression or death, HR=0.51 (95% CI:0.41-0.64), P<0.0001¹

Consistent results for PFS were observed across the prespecified subgroup of IMDC risk categories.¹

*PFS was assessed by BICR.¹

Study Design

A randomized (1:1), open-label, Phase 3 trial of CABOMETYX + OPDIVO vs sunitinib in 651 patients with previously untreated aRCC with a clear-cell component. The trial evaluated CABOMETYX 40 mg (starting dose) PO once daily in combination with OPDIVO. The primary endpoint was PFS, and secondary endpoints included OS, ORR, and safety. Quality of life was evaluated as an exploratory endpoint, the clinical significance is unknown.^1-3

OS outcomes show early and sustained separation of curves in the primary analysis²

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Pre-planned final analysis of OS (median follow-up: 32.9 months; range: 25.4-45.4 months): Median OS was 37.7 months for CABOMETYX + OPDIVO (95% Cl: 35.5-NR; n=323) compared with 34.3 months for sunitinib (95% Cl: 29.0-NR; n=328); HR=0.70 (95% Cl: 0.55-0.90).^1,4,5

Select Important Safety Information

The full Prescribing Information for CABOMETYX includes Warnings and Precautions for: hemorrhage, perforations and fistulas, thrombotic events, hypertension and hypertensive crises, diarrhea, palmar-plantar erythrodysesthesia (PPE), hepatotoxicity, adrenal insufficiency, proteinuria, osteonecrosis of the jaw, impaired wound healing, reversible posterior leukoencephalopathy syndrome, thyroid dysfunction, hypocalcemia, and embryo-fetal toxicity.

See additional important safety information below.

5-year follow-up analysis⁶

Median follow-up time of 67.6 months; range: 60.2-80.2 months⁶

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Median PFS: 16.4 months for CABOMETYX + OPDIVO (95% CI: 12.5-19.3; n=323) vs 8.3 months for sunitinib (95% CI: 7.0-9.7; n=328)⁶

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42% reduction of risk of progression or death, HR=0.58 (95% CI: 0.49-0.70)⁶

Longest available follow-up for
CheckMate-9ER

CABOMETYX + OPDIVO had a median OS of 46.5 months vs 35.5 months with sunitinib⁶

No formal statistical testing was conducted at the time of the updated analysis.

CheckMate-9ER Adverse Reactions

Serious adverse reactions occurred in 48% of patients receiving CABOMETYX and nivolumab. The most frequent (≥2%) serious adverse reactions were diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract infection, and hyponatremia. Fatal intestinal perforations occurred in 3 (0.9%) patients.¹

EXPLORE 5-YEAR DATA

1L=first-line; aRCC=advanced renal cell carcinoma; BICR=blinded independent central review; CI=confidence interval; HR=hazard ratio; IMDC=International Metastatic RCC Database Consortium; IO=immunotherapy; ITT=intent to treat; ORR=objective response rate; OS=overall survival; NR=not reached; PFS=progression-free survival; PO=by mouth.

INDICATION

CABOMETYX^® (cabozantinib), in combination with nivolumab, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. Discontinue CABOMETYX for Grade 3-4 hemorrhage and before surgery. Do not administer to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, and gastrointestinal (GI) perforations, including fatal cases, occurred in CABOMETYX patients. Monitor for signs and symptoms and discontinue in patients with Grade 4 fistulas or GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Fatal thrombotic events have occurred. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension including hypertensive crisis. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea may be severe. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1, resume at a reduced dose.

Palmar-Plantar Erythrodysesthesia (PPE): Withhold CABOMETYX until PPE resolves or decreases to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

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 withholding CABOMETYX and/or nivolumab, initiating corticosteroid therapy, and/or permanently discontinuing the combination for severe or life-threatening hepatotoxicity.

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.

Proteinuria: Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): 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. Withhold CABOMETYX for development of ONJ until complete resolution, resume at a reduced dose.

Impaired Wound Healing: Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer 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 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. Assess for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitor for signs and symptoms during treatment.

Hypocalcemia: 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 of the potential risk to fetus. Verify pregnancy status and advise use of effective contraception during treatment and for 4 months after last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

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 full Prescribing Information for additional important safety information.

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.

If you would like more information about CABOMETYX, please visit CABOMETYXhcp.com.

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References: 1. CABOMETYX^® (cabozantinib) Prescribing Information. Exelixis, Inc. 2. Choueiri TK, Powles T, Burotto M, et al; CheckMate 9ER Investigators. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384(9):829-841. 3. Motzer RJ, Choueiri TK, Powles T, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal cell carcinoma: outcomes by sarcomatoid histology and updated trial results with extended follow-up of CheckMate 9ER. Poster presented at Genitourinary Cancers Symposium; February 11-13, 2021. 4. Motzer RJ, Powles T, Burotto M, et al. Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomized, phase 3 trial. Lancet Oncol. 2022;23(7):888-898. 5. Powles T, Choueiri TK, Burotto M, et al. Final overall survival analysis and organ-specific target lesion assessments with 2-year follow-up in CheckMate 9ER: nivolumab plus cabozantinib versus sunitinib for patients with advanced renal cell carcinoma. Poster presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium; February 17-19, 2022. 6. Data on file. Exelixis, Inc.

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OPDIVO^® and the related logo are registered trademarks of Bristol-Myers Squibb Company.

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