Combining 2 proven agents* in aRCC1,2
OPDIVO® (nivolumab)
CABOMETYX® (cabozantinib)
Superior efficacy vs sunitinib across 3 key endpoints1†
Primary analysis results (median follow-up time of 18.1 months; range: 10.6–30.6 months).1,3
Overall response rate
Secondary endpoint1,3†‡
- ORR: 55.7% (n=180/323) (95% CI: 50.1–61.2) with OPDIVO + CABOMETYX vs 27.1% (n=89/328) (95% CI: 22.4–32.3) with sunitinib (P<0.0001)
- 8% (n=26/323) CR and 47.7% (n=154/323) PR for OPDIVO + CABOMETYX vs 4.6% (n=15/328) CR and 22.6% (n=74/328) PR for sunitinib3
Progression-free survival
Primary endpoint1,3†‡
- mPFS: 16.6 months (95% CI: 12.5–24.9) with OPDIVO + CABOMETYX vs 8.3 months (95% CI: 7.0–9.7) with sunitinib (HR=0.51; 95% CI: 0.41–0.64; P<0.0001)1,3
Overall survival
Secondary endpoint1†
- mOS: NR (95% CI: NR) with OPDIVO + CABOMETYX and NR (95% CI: 22.6–NR) with sunitinib (HR=0.60; 98.89% CI: 0.40–0.89; P=0.0010)1,3
Select Important Safety Information
Serious adverse reactions in Checkmate 9ER occurred in 46% of patients receiving OPDIVO and CABOMETYX (n=320). Serious adverse reactions reported in ≥2% of patients were diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract infection, and hyponatremia. Fatal intestinal perforations occurred in 3 (0.9%) patients.
In Checkmate 9ER, the most common adverse reactions (≥20%) in patients receiving OPDIVO and cabozantinib (n=320) were diarrhea (64%), fatigue (51%), hepatotoxicity (44%), palmar-plantar erythrodysaesthesia syndrome (40%), stomatitis (37%), rash (36%), hypertension (36%), hypothyroidism (34%), musculoskeletal pain (33%), decreased appetite (28%), nausea (27%), dysgeusia (24%), abdominal pain (22%), upper respiratory tract infection (20%), and cough (20%).
Please see additional Important Safety Information below and U.S. Full Prescribing Information for OPDIVO.
Extended follow-up analysis results (median follow-up time of 23.5 months; range: 16.0–36.0 months)4:
ORR‡: 54.8% (n=177/323 [95% CI: 49.2–60.3]) with OPDIVO + CABOMETYX vs 28.4% (n=93/328) [95% CI: 23.5–33.6]) with sunitinib; CR: 9.3% (n=30/323) with OPDIVO + CABOMETYX vs 4.3% (n=14/328) with sunitinib; PR: 45.5% (n=147/323) with OPDIVO + CABOMETYX vs 24.1% (n=79/328) with sunitinib; mPFS‡: 17.0 months (95% CI: 12.6–19.4) with OPDIVO + CABOMETYX vs 8.3 months (95% CI: 6.9–9.7) with sunitinib (HR=0.52; 95% CI: 0.43–0.64); mOS‡: NR (95% CI: NE) with OPDIVO + CABOMETYX and 29.5 months (95% CI: 28.4–NE) with sunitinib (HR=0.66; 95% CI: 0.50–0.87).
*OPDIVO as a single agent is indicated for the treatment of patients with advanced renal cell carcinoma (aRCC) who have received prior anti-angiogenic therapy.1 CABOMETYX is indicated for the treatment of patients with advanced renal cell carcinoma (aRCC).2
†Based on primary analysis results at a median follow-up of 18.1 months (range: 10.6–30.6 months).3
‡BICR assessed.1
aRCC=advanced renal cell carcinoma; BICR=blinded independent central review; CI=confidence interval; CR=complete response; HR=hazard ratio; mOS=median OS; mPFS=median PFS; NE=not estimable; NR=not reached; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; PR=partial response.
Study Design
When choosing I-O + TKI therapy in aRCC OPDIVO® + CABOMETYX® (cabozantinib) was studied in a phase 3, head-to-head trial vs sunitinib1,3
Checkmate 9ER includes data from an extended follow-up analysis at a median follow-up time of 23.5 months (range: 16.0–36.0 months)4
- Median follow-up time of the primary analysis was 18.1 months (range: 10.6–30.6 months)3
- Patients with autoimmune disease or other medical conditions requiring systemic immunosuppression were excluded from the trial1
- OPDIVO dosing was not to exceed a total of 2 years (from Cycle 1); CABOMETYX and sunitinib treatment was allowed to continue beyond 2 years in the absence of progression or unacceptable toxicity1,3
- Treatment beyond RECIST-defined disease progression was permitted if the patient was clinically stable and considered to be deriving clinical benefit by the investigator1
- Tumor assessments were performed at baseline, after randomization at Week 12, then every 6 weeks until Week 60, and then every 12 weeks thereafter1
†BICR assessed.3
‡Defined as the percent of positive tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 immunohistochemistry 28-8 pharmDx assay.3
§Approved dosing: OPDIVO 240 mg IV q2w or OPDIVO 480 mg IV q4w, in combination with CABOMETYX 40 mg PO qd without food. Continue OPDIVO until disease progression, unacceptable toxicity, or up to 2 years. Continue CABOMETYX until disease progression or unacceptable toxicity.1
IMDC=International Metastatic Renal Cell Carcinoma Database Consortium; I-O=immuno-oncology; IV=intravenous; PD-L1=programmed death-ligand 1; PO=by mouth; q2w=every 2 weeks; qd=every day; RECIST=Response Evaluation Criteria In Solid Tumors; TKI=tyrosine kinase inhibitor.
Overall Response Rate
When choosing I-O + TKI therapy in aRCC OPDIVO® + CABOMETYX® (cabozantinib): ORR vs sunitinib1,3,4*†‡
OPDIVO + CABOMETYX: ~90% DCR4†
- The FDA does not consider SD to be a valid endpoint for the measurement of response because it may reflect the natural history of disease rather than any effect of the drug5
- DCR was not pre-specified1
Median follow-up time of primary analysis was 18.1 months (range: 10.6–30.6 months)3
Complete and partial response rates
- 8% (n=26/323) CR and 47.7% (n=154/323) PR for OPDIVO + CABOMETYX vs 4.6%
Median follow-up time of extended follow-up analysis was 23.5 months (range: 16.0–36.0 months)4
Overall response rate‡
- 54.8% (n=177/323) ORR for OPDIVO + CABOMETYX (95% CI: 49.2–60.3) and 28.4% (n=93/328) for sunitinib (95% CI: 23.5–33.6)
Complete and partial response rates
- 9.3% (n=30/323) CR and 45.5% (n=147/323) PR for OPDIVO + CABOMETYX vs 4.3% (n=14/328) CR and 24.1% (n=79/328) PR for sunitinib
*Based on primary analysis results at a median follow-up of 18.1 months (range: 10.6–30.6 months).3
†Based on extended follow-up analysis results at a median follow-up of 23.5 months (range: 16.0–36.0 months).4
‡BICR assessed.1
DCR=disease control rate; SD=stable disease.
Progression-Free Survival
When choosing I-O + TKI therapy in aRCC OPDIVO® + CABOMETYX® (cabozantinib): The Only Approved I-O + TKI Combination to Double Median PFS1,3,4*†‡§
Median PFS§ at primary analysis (median follow-up time of 18 months; range 10.6–30.6 months)1,3
- OPDIVO + CABOMETYX: 16.6 months (95% CI: 12.5–24.9)
- Sunitinib: 8.3 months (95% CI: 7.0–9.7)
- HR=0.51 (95% CI: 0.41–0.64); P<0.0001
Median PFS§ at extended follow-up analysis (median follow-up time of 23.5 months; range: 16.0–36.0 months)4
- OPDIVO + CABOMETYX: 17.0 months (95% CI: 12.6–19.4)
- Sunitinib: 8.3 months (95% CI: 6.9–9.7)
- HR=0.52 (95% CI: 0.43–0.64)
*Based on primary analysis results at a median follow-up of 18.1 months (range: 10.6–30.6–months).3
†Based on extended follow-up analysis results at a median follow-up of 23.5 months (range: 16.0–36.0–months).4
‡vs sunitinib in the ITT population.1
§BICR assessed.1
ITT=intent to treat.
Overall Survival
When choosing I-O + TKI therapy in aRCC OPDIVO® + CABOMETYX® (cabozantinib): OS at ~2-year median follow-up1,3,4*
Median OS at primary analysis (median follow-up time of 18.1 months; range: 10.6–30.6 months)1,3
- OPDIVO + CABOMETYX: NR (95% CI: NR)
- Sunitinib: NR (95% CI: 22.6–NR)
- HR=0.60 (98.89% CI: 0.40–0.89); P=0.0010
Median OS at extended follow-up analysis (median follow-up time of 23.5 months; range: 16.0–36.0 months)4
- OPDIVO + CABOMETYX: NR (95% CI: NE)
- Sunitinib: 29.5 months (95% CI: 28.4–NE)
- HR=0.66 (95% CI: 0.50–0.87)
*Based on extended follow-up analysis results at a median follow-up of 23.5 months (range: 16.0–36.0 months).4
Dosing
OPDIVO + CABOMETYX: Flexible dosing options and a once-daily TKI1
- Based on exploratory dose exposure-response relationships for efficacy and safety, OPDIVO 240 mg q2w and 480 mg q4w are predicted to be similar6
- In combination with OPDIVO, the recommended starting dose for CABOMETYX is 40 mg. If needed, CABOMETYX may be interrupted or reduced to either 20 mg daily or
20 mg every other day1 - Review the Full Prescribing Information for both OPDIVO and CABOMETYX prior to initiation, including recommended dosage and dose modifications1
- No premedication required with OPDIVO + CABOMETYX1
¶OPDIVO is administered as an IV infusion over 30 minutes.1
q4w=every 4 weeks.
Selected Safety Profile
When choosing I-O + TKI therapy in aRCC What are your safety expectations for I-O + TKI therapy?
Grade 3–5 adverse reactions were similar with OPDIVO + CABOMETYX vs sunitinib (75% vs 71%)3
Reactions, %# Grade 1-4 adverse reactions occurring in ≥15% of patients receiving OPDIVO + CABOMETYX1 | OPDIVO + CABOMETYX (n=320)1 | Sunitinib (n=320)1 |
---|---|---|
Grades 1–5 (%) | Grades 1–5 (%) | |
All-cause adverse reactions3 | 100 | 99 |
General | ||
Fatigue** | 51 | 50 |
Hepatobiliary | ||
Hepatotoxicity†† | 44 | 26 |
Skin and Subcutaneous Tissue | ||
Palmar-plantar erythrodysesthesia syndrome | 40 | 41 |
Stomatitis‡‡ | 37 | 46 |
Rash§§ | 36 | 14 |
Pruritus | 19 | 4.4 |
Gastrointestinal | ||
Diarrhea | 64 | 47 |
Nausea | 27 | 31 |
Vomiting | 17 | 21 |
Abdominal pain*** | 22 | 15 |
Dyspepsia§§§ | 15 | 22 |
Musculoskeletal and Connective Tissue | ||
Musculoskeletal pain## | 33 | 29 |
Arthralgia | 18 | 9 |
Respiratory, Thoracic, and Mediastinal | ||
Cough††† | 20 | 17 |
Dysphonia | 17 | 3.4 |
Infections and Infestations | ||
Upper respiratory tract infection‡‡‡ | 20 | 8 |
Metabolism and Nutrition | ||
Decreased appetite | 28 | 20 |
Nervous System | ||
Dysgeusia | 24 | 22 |
Headache | 16 | 12 |
Endocrine | ||
Hypothyroidism¶¶ | 34 | 30 |
Vascular | ||
Hypertension|||| | 36 | 39 |
Reactions, %# Grade 1-4 adverse reactions in ≥15% of patients receiving OPDIVO + CABOMETYX1 | OPDIVO + CABOMETYX (n=320)1 | Sunitinib (n=320)1 |
---|---|---|
Grades 3–5 (%) | Grades 3–5 (%) | |
All-cause adverse reactions3 | 75 | 71 |
General | ||
Fatigue** | 8 | 8 |
Hepatobiliary | ||
Hepatotoxicity†† | 11 | 5 |
Skin and Subcutaneous Tissue | ||
Palmar-plantar erythrodysesthesia syndrome | 8 | 8 |
Stomatitis‡‡ | 3.4 | 4.4 |
Rash§§ | 3.1 | 0 |
Pruritus | 0.3 | 0 |
Gastrointestinal | ||
Diarrhea | 7 | 4.4 |
Nausea | 0.6 | 0.3 |
Vomiting | 1.9 | 0.3 |
Abdominal pain*** | 1.9 | 0.3 |
Dyspepsia§§§ | 0 | 0.3 |
Musculoskeletal and Connective Tissue | ||
Musculoskeletal pain## | 3.8 | 3.1 |
Arthralgia | 0.3 | 0.3 |
Respiratory, Thoracic, and Mediastinal | ||
Cough††† | 0.3 | 0 |
Dysphonia | 0.3 | 0 |
Infections and Infestations | ||
Upper respiratory tract infection‡‡‡ | 0.3 | 0.3 |
Metabolism and Nutrition | ||
Decreased appetite | 1.9 | 1.3 |
Nervous System | ||
Dysgeusia | 0 | 0 |
Headache | 0 | 0.6 |
Endocrine | ||
Hypothyroidism¶¶ | 0.3 | 0.3 |
Vascular | ||
Hypertension|||| | 13 | 14 |
Toxicity was graded per NCI CTCAE v4.1
#Includes events that occurred on therapy or within 30 days after the end of the treatment period of all treated patients.3
**Includes asthenia.1
††Includes hepatotoxicity, ALT increased, AST increased, blood alkaline phosphatase increased, gamma-glutamyl transferase increased, autoimmune hepatitis, blood bilirubin increased, drug induced liver injury, hepatic enzyme increased, hepatitis, hyperbilirubinemia, liver function test increased, liver function test abnormal, transaminases increased, hepatic failure.1
‡‡Includes mucosal inflammation, aphthous ulcer, mouth ulceration.1
§§Includes dermatitis, dermatitis acneiform, dermatitis bullous, exfoliative rash, rash erythematous, rash follicular, rash macular, rash maculo-papular, rash papular, rash pruritic.1
||||Includes blood pressure increased, blood pressure systolic increased.1
¶¶Includes primary hypothyroidism.1
##Includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, myalgia, neck pain, pain in extremity, spinal pain.1
***Includes abdominal discomfort, abdominal pain lower, abdominal pain upper.1
†††Includes productive cough.1
‡‡‡Includes nasopharyngitis, pharyngitis, rhinitis.1
§§§Includes gastroesophageal reflux disease.1
ALT=alanine aminotransferase; AST=aspartate aminotransferase; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.
due to the same adverse reaction occurring at the same time1,8:
OPDIVO AND CABOMETYX 5.6%
- Adverse reactions leading to discontinuation of either OPDIVO or CABOMETYX occurred in 19.7% of patients: 6.6% OPDIVO only, 7.5% CABOMETYX only, and 5.6% OPDIVO + CABOMETYX due to same adverse reaction at the same time1,8
- Adverse reactions leading to dose interruption or reduction of either OPDIVO or CABOMETYX occurred in 83% of patients: 3% OPDIVO only, 46% CABOMETYX only, 21% both drugs due to same adverse reaction at the same time, and 6% both drugs sequentially1
- Serious adverse reactions in Checkmate 9ER occurred in 48% of patients receiving OPDIVO and CABOMETYX. Serious adverse reactions reported in ≥2% of patients were diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract infection, and hyponatremia. Fatal intestinal perforations occurred in 3 (0.9%) patients1
- The most common adverse reactions (>20%) reported in patients receiving OPDIVO + CABOMETYX were diarrhea (64%), fatigue (51%), hepatotoxicity (44%), palmar-plantar erythrodysaesthesia syndrome (40%), stomatitis (37%), rash (36%), hypertension (36%), hypothyroidism (34%), musculoskeletal pain (33%), decreased appetite (28%), nausea (27%), dysgeusia (24%), abdominal pain (22%), upper respiratory tract infection (20%), and cough (20%)1
Laboratory values worsening from baseline in >20% of patients on OPDIVO and CABOMETYX1
Percentage of patients with worsening laboratory tests from baseline1||||||
Laboratory abnormality | OPDIVO + CABOMETYX | Sunitinib | ||
---|---|---|---|---|
Grades 1–4 (%) | Grades 3–4 (%) | Grades 1–4 (%) | Grades 3–4 (%) | |
Chemistry | ||||
Increased ALT | 79 | 9.8 | 39 | 3.5 |
Increased AST | 77 | 7.9 | 57 | 2.6 |
Hypophosphatemia | 69 | 28 | 48 | 10 |
Hypocalcemia | 54 | 1.9 | 24 | 0.6 |
Hypermagnesemia | 47 | 1.3 | 25 | 0.3 |
Hyperglycemia | 44 | 3.5 | 44 | 1.7 |
Hyponatremia | 43 | 11 | 36 | 12 |
Increased lipase | 41 | 14 | 38 | 13 |
Increased amylase | 41 | 10 | 28 | 6 |
Increased alkaline phosphatase | 41 | 2.8 | 37 | 1.6 |
Increased creatinine | 39 | 1.3 | 42 | 0.6 |
Hyperkalemia | 35 | 4.7 | 27 | 1 |
Hypoglycemia | 26 | 0.8 | 14 | 0.4 |
Hematology | ||||
Lymphopenia | 42 | 6.6 | 45 | 10 |
Thrombocytopenia | 41 | 0.3 | 70 | 9.7 |
Anemia | 37 | 2.5 | 31 | 4.8 |
Leukopenia | 37 | 0.3 | 66 | 5.1 |
Neutropenia | 35 | 3.2 | 67 | 12 |
Laboratory abnormality | OPDIVO + CABOMETYX | Sunitinib |
---|---|---|
Grades 1–4 (%) | Grades 1–4 (%) | |
Chemistry | ||
Increased ALT | 79 | 39 |
Increased AST | 77 | 57 |
Hypophosphatemia | 69 | 48 |
Hypocalcemia | 54 | 24 |
Hypermagnesemia | 47 | 25 |
Hyperglycemia | 44 | 44 |
Hyponatremia | 43 | 36 |
Increased lipase | 41 | 38 |
Increased amylase | 41 | 28 |
Increased alkaline phosphatase | 41 | 37 |
Increased creatinine | 39 | 42 |
Hyperkalemia | 35 | 27 |
Hypoglycemia | 26 | 14 |
Hematology | ||
Lymphopenia | 42 | 45 |
Thrombocytopenia | 41 | 70 |
Anemia | 37 | 31 |
Leukopenia | 37 | 66 |
Neutropenia | 35 | 67 |
Laboratory abnormality | OPDIVO + CABOMETYX | Sunitinib |
---|---|---|
Grades 3–4 (%) | Grades 3–4 (%) | |
Chemistry | ||
Increased ALT | 9.8 | 3.5 |
Increased AST | 7.9 | 2.6 |
Hypophosphatemia | 28 | 10 |
Hypocalcemia | 1.9 | 0.6 |
Hypermagnesemia | 1.3 | 0.3 |
Hyperglycemia | 3.5 | 1.7 |
Hyponatremia | 11 | 12 |
Increased lipase | 14 | 13 |
Increased amylase | 10 | 6 |
Increased alkaline phosphatase | 2.8 | 1.6 |
Increased creatinine | 1.3 | 0.6 |
Hyperkalemia | 4.7 | 1 |
Hypoglycemia | 0.8 | 0.4 |
Hematology | ||
Lymphopenia | 6.6 | 10 |
Thrombocytopenia | 0.3 | 9.7 |
Anemia | 2.5 | 4.8 |
Leukopenia | 0.3 | 5.1 |
Neutropenia | 3.2 | 12 |
||||||Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: OPDIVO + CABOMETYX group (range: 170 to 317 patients) and sunitinib group (range: 173 to 311 patients).1
- In the 23.5-month extended follow-up analysis, all-cause laboratory abnormalities occurring in >20% of patients receiving OPDIVO + CABOMETYX and not previously included in the primary analysis include: hypokalemia (OPDIVO + CABOMETYX: 21.8% Grades 1-4, 3.2% Grades 3-4; sunitinib: 12.6% Grades 1-4, 1.6% Grades 3–4)1,7