Two 1L aRCC combinations
based on OPDIVO® (nivolumab)1
Select an OPDIVO-based treatment option to view clinical information
Please see OPDIVO + CABOMETYX data below.
*vs sunitinib in the ITT population.
†BICR assessed.1
1L=first-line; aRCC=advanced renal cell carcinoma; CI=confidence interval; HR=hazard ratio; I-O=immuno-oncology; ITT=intent to treat; mPFS=median progression-free survival; TKI=tyrosine kinase inhibitor.
In the extended follow-up analysis of Checkmate 214 (minimum follow-up time of 48 months):
- mOS:
- The 48-month OS rate for OPDIVO + YERVOY was 50.0% vs 35.8% for sunitinib. OPDIVO + YERVOY: 48.1 months (95% CI: 35.6-NE)2
- Sunitinib: 26.6 months (95% CI: 22.1-33.5)2
- HR=0.65 (95% CI: 0.54-0.78)2
In the primary analysis of Checkmate 214 (median follow-up time of 25.2 months):
- Median OS not yet reached (95% CI: 28.2–NE) for OPDIVO + YERVOY vs 25.9 months (95% CI: 22.1–NE) for sunitinib; HR=0.63 (99.8% CI: 0.44–0.89); P<0.00011,4
- Median PFS†: 11.6 months (95% CI: 8.7–15.5) for OPDIVO + YERVOY vs 8.4 months (95% CI: 7.0–10.8) for sunitinib; HR=0.82 (99.1% CI: 0.64–1.05)1,4
- Per pre-specified analysis, progression-free survival did not meet statistical significance1,4
- Confirmed ORR†: 41.6% (n=177/425) (95% CI: 36.9–46.5) for OPDIVO + YERVOY vs 26.5% (n=112/422) (95% CI: 22.4–31.0) for sunitinib (P<0.0001)1,4
- CR: 9.4% (n=40) for OPDIVO + YERVOY vs 1.2% (n=5) for sunitinib1,4
- PR: 32.2% (n=137) for OPDIVO + YERVOY vs 25.4% (n=107) for sunitinib1,4
Checkmate 214 Study Design1,4
Checkmate 214 was a phase 3, randomized (1:1), open-label study of OPDIVO 3 mg/kg IV and YERVOY 1 mg/kg IV (n=425) every 3 weeks for 4 doses, followed by OPDIVO 3 mg/kg IV every 2 weeks‡ vs sunitinib (n=422) 50 mg administered orally once daily for 4 weeks, followed by 2 weeks off every cycle, in patients with previously untreated intermediate/poor risk aRCC. Patients were stratified by IMDC prognostic score and region, and treatment was continued until disease progression or unacceptable toxicity. The co-primary endpoints in IMDC intermediate/poor risk patients were OS, ORR,† and PFS.1,4†
In the primary analysis of Checkmate 9ER (median follow-up of 18.1 months [range: 10.6–30.6 months]):
- mPFS† was 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
In the extended follow-up analysis of Checkmate 9ER (median follow-up of 23.5 months):
- mPFS† was 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).4
Checkmate 9ER Study Design
Checkmate 9ER was a phase 3, randomized (1:1), open-label study of OPDIVO 240 mg/kg IV every 2 weeks|| and CABOMETYX 40 mg orally once daily (n=323) vs sunitinib 50 mg administered orally once daily (n=328) for the first 4 weeks of a 6-week cycle (4 weeks of treatment followed by 2 weeks off) in patients with previously untreated aRCC. Patients were stratified by IMDC prognostic score, PD-L1 tumor expression, and region, and treatment was continued until disease progression or unacceptable toxicity. Treatment beyond RECIST-defined disease progression was permitted if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. Tumor assessments were performed at baseline, after randomization at Week 12, then every 6 weeks until Week 60, and then every 12 weeks thereafter. The primary endpoint was PFS (BICR assessed). Secondary endpoints were OS and ORR (BICR assessed).1,3
Checkmate 214 Study Design1,4
Checkmate 214 was a phase 3, randomized (1:1), open-label study of OPDIVO 3 mg/kg IV and YERVOY 1 mg/kg IV (n=425) every 3 weeks for 4 doses, followed by OPDIVO 3 mg/kg IV every 2 weeks‡ vs sunitinib (n=422) 50 mg administered orally once daily for 4 weeks, followed by 2 weeks off every cycle, in patients with previously untreated intermediate/poor risk aRCC. Patients were stratified by IMDC prognostic score and region, and treatment was continued until disease progression or unacceptable toxicity. The co-primary endpoints in IMDC intermediate/poor risk patients were OS, ORR,§ and PFS.1,4§
†BICR assessed.1
‡The recommended dose of OPDIVO in combination with YERVOY is OPDIVO 3 mg/kg administered as an IV infusion over 30 minutes, followed by YERVOY 1 mg/kg administered as an IV infusion over 30 minutes on the same day, every 3 weeks for 4 doses. The recommended subsequent dose of OPDIVO as a single agent is either 240 mg or 480 mg administered as an IV infusion over 30 minutes every 2 weeks or 4 weeks, respectively, until disease progression or unacceptable toxicity.1
||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
§PFS and ORR were assessed by an independent radiographic review committee per RECIST v1.1.1,4
CR=complete response; IMDC=International Metastatic Renal Cell Carcinoma Database Consortium; IV=intravenous; mOS=median OS; NE=not evaluable; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumors.
Select Important Safety Information
Serious Adverse Reactions
In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY (n=547). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis. In Checkmate 9ER, serious adverse reactions occurred in 46% of patients receiving OPDIVO and cabozantinib (n=320). The most frequent 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.
Common Adverse Reactions
Checkmate 214, the most common adverse reactions (≥20%) reported in patients treated with OPDIVO plus YERVOY (n=547) were fatigue (58%), rash (39%), diarrhea (38%), musculoskeletal pain (37%), pruritus (33%), nausea (30%), cough (28%), pyrexia (25%), arthralgia (23%), decreased appetite (21%), dyspnea (20%), and vomiting (20%). 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%), cough (20%) and upper respiratory tract infection (20%).
Please see additional Important Safety Information below and U.S. Full Prescribing Information for OPDIVO and YERVOY.