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Full Indication

For Patients With Previously Untreated Intermediate
or Poor Risk Advanced Renal Cell Carcinoma

OPDIVO® (nivolumab) +
YERVOY® (ipilimumab):
A CHANCE AT EARLY RESPONSES.
A POSSIBILITY FOR DURABLE RESPONSES
AND LONG-TERM SURVIVAL.1-4*†

*Based on primary analysis results
from Checkmate 214.1,2
†Based on
results from an extended follow-up
analysis at a minimum of 42 months.4

Checkmate 214 Primary Analysis

Median follow-up time of 25.2 months

Scroll to see additional information, including primary and extended
follow-up data below

In the primary analysis of Checkmate 214:

In the primary analysis of Checkmate 214 (median follow-up time of 25.2 months):

  • Confirmed ORR‡: 41.6% (n=177) (95% CI: 36.9–46.5) for OPDIVO + YERVOY vs 26.5% (n=112) (95% CI: 22.4–31.0) for sunitinib (P<0.0001)1,3
    • CR: 9.4% (n=40) for OPDIVO + YERVOY vs 1.2% (n=5) for sunitinib1,3
    • PR: 32.2% (n=137) for OPDIVO + YERVOY vs 25.4% (n=107) for sunitinib1,3
    • Median DOR in the primary analysis was not evaluable (NE) for OPDIVO + YERVOY (95% CI: 21.8–NE) vs 18.2 months for sunitinib (95% CI: 14.8–NE)1,3
    • Among responders, median TTR was 12.2 weeks (range: 3.9–49.1) for OPDIVO + YERVOY vs 13.0 weeks (range: 2.6–65.2) for sunitinib1,3
  • Median OS not yet reached for OPDIVO + YERVOY
    (95% CI: 28.2–NE) vs 25.9 months for sunitinib (95% CI: 22.1–NE); HR=0.63 (99.8% CI: 0.44–0.89); P<0.00011,3
  • 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)1,3
    • Per pre-specified analysis, progression-free survival did not meet statistical significance1,3

‡PFS and ORR were assessed by an independent radiographic review committee per RECIST v1.1.1,3

Scroll to see additional information,
including extended follow-up data below

Select Important Safety Information

  • In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY and in 43% of patients receiving sunitinib. 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 patients treated with sunitinib, they were pneumonia, pleural effusion, and dyspnea.
  • In Checkmate 214, the most common adverse reactions (≥20%) reported in patients treated with OPDIVO plus YERVOY (n=547) vs sunitinib (n=535) were fatigue (58% vs 69%), rash (39% vs 25%), diarrhea (38% vs 58%), musculoskeletal pain (37% vs 40%), pruritus (33% vs 11%), nausea (30% vs 43%), cough (28% vs 25%), pyrexia (25% vs 17%), arthralgia (23% vs 16%), decreased appetite (21% vs 29%), dyspnea (20% vs 21%), and vomiting (20% vs 28%).

Please see additional Important Safety Information below and U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.

VIEW THE CHECKMATE 214
STUDY DESIGN
Click or tap the tabs to view
additional data.
expand allclose all
 
 

Baseline Characteristics

Checkmate 214 baseline characteristics1,3,5 IMDC intermediate or poor risk patients.

CharacteristicOPDIVO + YERVOY
(n=425)		Sunitinib
(n=422)

Median age, years3,5

≥65 years, %
≥75 years, %

62
38
8		61
39
7

Male, %3

7471

IMDC prognostic score, %3

Intermediate (1–2)
Poor (3–6)

79
21		79
21

No. of sites with ≥1 target/non-target lesion, %3

1
≥2

21
79		20
80

Quantifiable tumor PD-L1 expression, %3

<1%
≥1%

(n=384)
74
26		(n=392)
71
29

Most common site of metastasis, %3

Lung
Lymph node
Bone
Liver

69
45
22
21		70
51
23
21
CharacteristicOPDIVO + YERVOY
(n=425)		Sunitinib
(n=422)

Median age, years3,5

≥65 years, %
≥75 years, %

62
38
8		61
39
7

Male, %3

7471

IMDC prognostic score, %3

Intermediate (1–2)
Poor (3–6)

79
21		79
21

No. of sites with ≥1 target/
non-target lesion, %3

1
≥2

21
79		20
80

Quantifiable tumor PD-L1 expression, %3

<1%
≥1%

(n=384)
74
26		(n=392)
71
29

Most common site of metastasis, %3

Lung
Lymph node
Bone
Liver

69
45
22
21		70
51
23
21
An overview of Checkmate 214, a phase 3 study for IMDC intermediate or poor risk advanced renal cell carcinoma patients taking OPDIVO® (nivolumab) + YERVOY® (ipilimumab) versus IMDC intermediate or poor risk patients taking sunitinib. An overview of Checkmate 214, a phase 3 study for IMDC intermediate or poor risk advanced renal cell carcinoma patients taking OPDIVO® (nivolumab) + YERVOY® (ipilimumab) versus IMDC intermediate or poor risk patients taking sunitinib.

§Of evaluable patients (n=284/384).3

Approximately 75%-80% of
1L aRCC patients qualify as
intermediate or poor risk3,6-8||

||Based on large, retrospective, population-based studies.6-8

 

IMDC Risk Factors

Up to 80% of 1L aRCC patients qualify as intermediate or poor risk3,6-8||

Intermediate or poor risk patients have ≥1 prognostic risk factor per the IMDC criteria3,6

Risk factors from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Risk factors from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

||Based on large, retrospective, population-based studies.6-8

Extended Follow-Up Data
 

Overall Response Rate
(CR, PR, and mDOR)

In an extended follow-up analysis at a minimum of 42 months in 1L intermediate/poor risk aRCC patients

The first and only I-O combination with complete response data at 42 months4,9¶

Ongoing complete responses for the phase 3 Checkmate 214 trial of first-line OPDIVO® (nivolumab) + YERVOY® (ipilimumab) versus sunitinib in patients with intermediate or poor risk advanced renal cell carcinoma. Ongoing complete responses for the phase 3 Checkmate 214 trial of first-line OPDIVO® (nivolumab) + YERVOY® (ipilimumab) versus sunitinib in patients with intermediate or poor risk advanced renal cell carcinoma.

ORR# at extended follow-up analysis (minimum follow-up time of 42 months)9

  • OPDIVO + YERVOY: ORR: 42.1% (95% CI: 37.4–47.0) (n=179/425); CR: 10.1% (n=43/425);
    PR: 32.0% (n=136/425)9
  • Sunitinib: ORR: 26.3% (95% CI: 22.2–30.8) (n=111/422); CR: 1.4% (n=6/422); PR: 24.9% (n=105/422)9

Median DOR was not yet reached at a median follow-up of 42 months12

Median duration of response with OPDIVO® (nivolumab) + YERVOY® (ipilimumab) for intermediate or poor risk advanced renal cell carcinoma treatment compared to sunitinib. Median duration of response with OPDIVO® (nivolumab) + YERVOY® (ipilimumab) for intermediate or poor risk advanced renal cell carcinoma treatment compared to sunitinib.

ORR# at primary analysis (median follow-up time of 25.2 months)1,3

  • OPDIVO + YERVOY: ORR: 41.6% (n=177/425 [95% CI: 36.9–46.5]; CR: 9.4% [n=40], PR: 32.2% [n=137])1,3
  • Sunitinib: ORR: 26.5% (n=112/422 [95% CI: 22.4–31.0]; CR: 1.2% [n=5], PR: 25.4% [n=107])1,3
  • P<0.0001 for ORR1

In a phase 3 trial.3,4

#At both the primary analysis and extended follow-up analysis, ORR was assessed by an independent radiographic review committee per RECIST v1.1.1,3,9

**This study is ongoing but no longer recruiting.13

 

Overall Survival

In an extended follow-up analysis at a minimum of 42 months in 1L intermediate/poor risk aRCC patients

The only I-O combination with more than 50% of patients alive at 42 months4††

Checkmate 214:
Overall survival in intermediate or
poor risk patients1,3,4‡‡

Kaplan-Meier Curve of overall survival in intermediate or poor risk advanced renal cell carcinoma patients taking OPDIVO® (nivolumab) + YERVOY® (ipilimumab) versus patients taking sunitinib Kaplan-Meier Curve of overall survival in intermediate or poor risk advanced renal cell carcinoma patients taking OPDIVO® (nivolumab) + YERVOY® (ipilimumab) versus patients taking sunitinib

The 18-month, 30-month, and 42-month overall survival rate analyses were not pre-specified within
study protocol.12 In the primary analysis, the pre-specified 12-month overall survival rate was 80%
(95% CI: 76–84) with OPDIVO + YERVOY vs 72% (95% CI: 67–76) with sunitinib. The median
follow-up time was 25.2 months.3,12

mOS at extended follow-up (minimum follow-up time of 42 months)4

  • OPDIVO + YERVOY: 47.0 months (95% CI: 35.6–NE)4
  • Sunitinib: 26.6 months (95% CI: 22.1–33.5)4
  • HR=0.66 (95% CI: 0.55–0.80)4

††In a phase 3 trial.3,4

‡‡Performance status is based on IMDC prognostic score (0=favorable, 1-2=intermediate, 3+=poor).3

SELECT Safety Information
 

Selected Safety Profile

Checkmate 214: Selected safety profile1

Optimized dosing resulted in fewer overall Grade 3-4 adverse reactions in
the OPDIVO + YERVOY arm vs sunitinib (65% vs 76%)1

 OPDIVO + YERVOY
(n=547)		Sunitinib
(n=535)
Adverse reactionsGrades 1-4Grades 3-4Grades 1-4Grades 3-4

Adverse reactions, %

All causes

99659976

General disorders and
administration site
conditions, %

Fatigue‡‡
Pyrexia
Edema§§

58
25
16		8
0.7
0.5		69
17
17		13
0.6
0.6

Respiratory, thoracic, and mediastinal disorders, %

Cough/productive cough Dyspnea/exertional dyspnea

28
20		0.2
2.4		25
21		0.4
2.1

Gastrointestinal disorders, %

Diarrhea
Nausea
Vomiting
Abdominal pain
Constipation

38
30
20
19
17		4.6
2.0
0.9
1.6
0.4		58
43
28
24
18		6
1.5
2.1
1.9
0

Skin and subcutaneous
tissue disorders, %

Rash||||
Pruritus/generalized pruritus

39
33		3.7
0.5		25
11		1.1
0

Endocrine disorders, %

Hypothyroidism

180.4270.2

Nervous system disorders, %

Headache

190.9230.9

Metabolism and
nutrition disorders, %

Decreased appetite

211.8290.9

Musculoskeletal and connective tissue disorder, %

Musculoskeletal pain¶¶ Arthralgia

37
23		4.0
1.3		40
16		2.6
0
 OPDIVO + YERVOY
(n=547)		Sunitinib
(n=535)
Adverse
reactions		Grades
1-4		Grades
1-4

Adverse
reactions, %

All causes

9999

General
disorders and
administration
site
conditions, %

Fatigue‡‡
Pyrexia
Edema§§

58
25
16		69
17
17

Respiratory, thoracic, and mediastinal disorders, %

Cough/
productive
cough
Dyspnea/
exertional dyspnea

28


20		25


21

Gastrointestinal disorders, %

Diarrhea
Nausea
Vomiting
Abdominal pain
Constipation

38
30
20
19
17		58
43
28
24
18

Skin and subcutaneous tissue
disorders, %

Rash||||
Pruritus/
generalized pruritus

39


33		25


11

Endocrine disorders, %

Hypothyroidism

1827

Nervous
system
disorders, %

Headache

1923

Metabolism
and nutrition
disorders, %

Decreased appetite

2129

Musculo-
skeletal and connective tissue
disorder, %

Musculo-
skeletal pain¶¶ Arthralgia

37
23		40
16
 OPDIVO + YERVOY
(n=547)		Sunitinib
(n=535)
Adverse
reactions		Grades
3-4		Grades
3-4

Adverse
reactions, %

All causes

6576

General
disorders and
administration
site
conditions, %

Fatigue‡‡
Pyrexia
Edema§§

8
0.7
0.5		13
0.6
0.6

Respiratory, thoracic, and mediastinal disorders, %

Cough/
productive
cough
Dyspnea/
exertional dyspnea

0.2


2.4		0.4


2.1

Gastrointestinal disorders, %

Diarrhea
Nausea
Vomiting
Abdominal pain
Constipation

4.6
2.0
0.9
1.6
0.4		6
1.5
2.1
1.9
0

Skin and subcutaneous tissue
disorders, %

Rash||||
Pruritus/
generalized pruritus

3.7


0.5		1.1


0

Endocrine disorders, %

Hypothyroidism

0.40.2

Nervous
system
disorders, %

Headache

0.90.9

Metabolism
and nutrition
disorders, %

Decreased appetite

1.80.9

Musculo-
skeletal and connective tissue
disorder, %

Musculo-
skeletal pain¶¶ Arthralgia

4.0
1.3		2.6
0
  • Safety outcomes in 42-month follow up analysis: All-cause adverse events occurring in >15% of patients receiving OPDIVO + YERVOY and not previously included in the primary analysis is: upper respiratory tract infection (OPDIVO + YERVOY: 21.2% Grades 1-4, 0.4% Grades 3-4; sunitinib: 14.4% Grades 1-4)1,13

Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.

‡‡Includes asthenia.

§§Includes peripheral edema, peripheral swelling.

||||Includes dermatitis described as acneiform, bullous, and exfoliative, drug eruption, rash described as exfoliative,
erythematous, follicular, generalized, macular, maculopapular, papular, pruritic, and pustular, fixed-drug eruption.

¶¶Includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, myalgia, neck pain, pain in extremity,
spinal pain.

Checkmate 214: Grade 1-4 laboratory abnormalities that occurred
in >15% of patients on OPDIVO + YERVOY1

Percentage of patients with worsening laboratory test from baseline##

 OPDIVO + YERVOY
(n=547)		Sunitinib
(n=535)
Laboratory abnormalitiesGrades 1-4Grades 3-4Grades 1-4Grades 3-4

Hematology

Anemia
Lymphopenia

43
36		3
5		64
63		9
14

Chemistry

Increased lipase
Increased creatinine
Increased ALT
Increased AST
Increased amylase
Hyponatremia
Increased alkaline phosphatase
Hyperkalemia
Hypocalcemia
Hypomagnesemia

48
42
41
40
39
39
29
29
21
16		20
2.1
7
4.8
12
10
2
2.4
0.4
0.4		51
46
44
60
33
36
32
28
35
26		20
1.7
2.7
2.1
7
7
1
2.9
0.6
1.6
 OPDIVO + YERVOY
(n=547)		Sunitinib
(n=535)
Laboratory abnormalitiesGrades
1-4		Grades
1-4

Hematology

Anemia
Lymphopenia

43
36		64
63

Chemistry

Increased lipase
Increased creatinine
Increased ALT
Increased AST
Increased amylase
Hyponatremia
Increased
alkaline
phosphatase
Hyperkalemia
Hypocalcemia
Hypo-
magnesemia

48

42
41
40

39
39


29
29
21

16		51

46
44
60

33
36


32
28
35

26
 OPDIVO + YERVOY
(n=547)		Sunitinib
(n=535)
Laboratory abnormalitiesGrades
3-4		Grades
3-4

Hematology

Anemia
Lymphopenia

3
5		9
14

Chemistry

Increased lipase
Increased creatinine
Increased ALT
Increased AST
Increased amylase
Hyponatremia
Increased
alkaline
phosphatase
Hyperkalemia
Hypocalcemia
Hypo-
magnesemia

20

2.1
7
4.8

12
10


2
2.4
0.4

0.4		20

1.7
2.7
2.1

7
7


1
2.9
0.6

1.6

##Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory
measurement available: OPDIVO + YERVOY group (range: 490–538 patients) and sunitinib group (range: 485–523 patients).1

 In addition, among patients with TSH less than or equal to the ULN at baseline, a lower proportion of patients experienced
a treatment-emergent elevation of TSH greater than the ULN in the OPDIVO + YERVOY group compared to the sunitinib
group (31% and 61%, respectively).1

  • A lower incidence of overall Grade 3–4 adverse reactions occurred with OPDIVO + YERVOY vs
    sunitinib (65% and 76%, respectively)1
  • Treatment discontinuation rate due to adverse reactions was 31% with OPDIVO + YERVOY vs 21%
    with sunitinib1,14
  • Dose interruption due to adverse reactions occurred in 54% of patients receiving OPDIVO +
    YERVOY and 43% receiving sunitinib1,15
    • In the sunitinib group, 53% of patients required a dose reduction; dose reductions were not
      permitted in the OPDIVO + YERVOY treatment group16
  • Serious adverse reactions occurred in 59% of patients receiving OPDIVO + YERVOY and in 43% of
    patients receiving sunitinib1,17
    • The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO +
      YERVOY were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury,
      dyspnea, adrenal insufficiency, and colitis; for sunitinib, they were pneumonia, pleural effusion,
      and dyspnea1
  • The most common adverse reactions (reported in at least 20% of OPDIVO + YERVOY-treated
    patients) were fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia,
    arthralgia, decreased appetite, dyspnea, and vomiting1
 

IMAR Safety Management Resources

The OPDIVO Safety Tool is a quick reference to the immune-mediated adverse reactions (IMARs) associated with OPDIVO treatment. You may access this web app from your phone, tablet, or computer.

View the OPDIVO Safety Tool
Resources
 

OPDIVO HCP RESOURCES

Contact us at 1-855-OPDIVO-1
BMS Access Support® Bristol-Myers Squibb Resources
View dosing information for OPDIVO + YERVOY for 1L intermediate or poor risk aRCC

1L=first-line; ALT=alanine aminotransferase; aRCC=advanced renal cell carcinoma; AST=aspartate aminotransferase;
CI=confidence interval; CR=complete response; DOR=duration of response; HR=hazard ratio; IMDC=International Metastatic
Renal Cell Carcinoma Database Consortium; I-O=immuno-oncology; IV=intravenous; LLN=lower limit of normal;
mDOR=median duration of response; NE=not evaluable; No.=number; ORR=overall response rate; OS=overall survival;
PD-L1=programmed death-ligand 1; PFS=progression-free survival; PR=partial response; PS=performance score;
RCC=renal cell carcinoma; RECIST=Response Evaluation Criteria In Solid Tumors; TSH=thyroid-stimulating hormone; ULN=upper limit of normal.

OPDIVOYERVOY
OPDIVOYERVOY
More Important Safety Information Collapse

Select Important Safety 
Information

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-medicated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Important Safety Information

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy, and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests, at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

Immune-Mediated Pneumonitis

  • OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 4.4% (24/547) of patients.

Immune-Mediated Colitis

  • OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated colitis occurred in 10% (52/547) of patients.
  • Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis.
    In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Addition of an alternative immunosuppressive agent to the corticosteroid therapy, or replacement of the corticosteroid therapy, should be considered in corticosteroid-refractory immune-mediated colitis if other causes are excluded.

Immune-Mediated Hepatitis

  • OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated hepatitis occurred in 7% (38/547) of patients.

Immune-Mediated Endocrinopathies

  • OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.
  • In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypophysitis occurred in 4.6% (25/547) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, adrenal insufficiency occurred in 7% (41/547) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (119/547) of patients. Hyperthyroidism occurred in 12% (66/547) of patients receiving this dose of OPDIVO with YERVOY.
    In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, diabetes occurred in 2.7% (15/547) of patients.

Immune-Mediated Nephritis and Renal Dysfunction

  • OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated nephritis and renal dysfunction occurred in 4.6% (25/547) of patients.

Immune-Mediated Skin Adverse Reactions

  • OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated rash occurred in 16% (90/547) of patients.

Immune-Mediated Encephalitis

  • OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. Encephalitis occurred in one RCC patient receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg (0.2%) after approximately 4 months of exposure.

Other Immune-Mediated Adverse Reactions

  • Based on the severity of the adverse reaction, permanently discontinue or withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO monotherapy or in combination with YERVOY, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1.0% of patients receiving OPDIVO: myocarditis, rhabdomyolysis, myositis, uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), motor dysfunction, vasculitis, aplastic anemia, pericarditis, and myasthenic syndrome.
  • If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, which has been observed in patients receiving OPDIVO and may require treatment with systemic steroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

  • OPDIVO can cause severe infusion-related reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion-related reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO.
  • In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related reactions occurred in 5.1% (28/547) of patients.

Embryo-Fetal Toxicity

  • Based on mechanism of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO or YERVOY and for at least 5 months after the last dose.

Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone

  • In clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Lactation

  • It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from OPDIVO or YERVOY, advise women not to breastfeed during treatment and for at least 5 months after the last dose.

Serious Adverse Reactions

  • In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY. 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.

Common Adverse Reactions

  • In 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%).

OPDIVO (10 mg/mL) and YERVOY (5 mg/mL) are injections for intravenous (IV) use.

Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.

References:

  1. OPDIVO [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.
  2. YERVOY [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.
  3. Motzer RJ, Tannir NM, McDermott DF, et al; for CheckMate 214 Investigators. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277-1290.
  4. Tannir NM, McDermott DF, Escudier B, et al. Overall survival and independent review of response in CheckMate 214 with 42-month follow-up: first-line nivolumab + ipilimumab versus sunitinib in patients with advanced renal cell carcinoma. Oral presentation at ASCO GU 2020. Abstract 609.
  5. Data on file. NIVO 441. Princeton, NJ:
    Bristol-Myers Squibb Company; 2019.
  6. Heng DY, Xie W, Regan MM, et al. External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013;14(2):141-148.
  7. Ko JJ, Xie W, Kroeger N, et al. The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol. 2015;16(3):293-300.
  8. Yip SM, Wells C, Moreira R, et al. Real world experience of immuno-oncology agents in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Poster presentation at ASCO GU 2017. Abstract 492.
  9. Data on file. NIVO 544. Princeton, NJ: Bristol-Myers Squibb Company; 2020.
  10. Tannir NM, McDermott DF, Escudier B, et al. Overall survival and independent review of response in CheckMate 214 with 42-month follow-up: first-line nivolumab + ipilimumab (N+I) versus sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC). J Clin Oncol. 2020;38(suppl 6). Abstract 609. https://meetinglibrary.asco.org/record/184103/abstract. Accessed February 19, 2020.
  11. Data on file. NIVO 548. Princeton, NJ: Bristol-Myers Squibb Company; 2020.
  12. Motzer RJ, Tannir NM, McDermott DF, et al; for CheckMate 214 Investigators. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277-1290 [protocol].
  13. Data on file. NIVO 545. Princeton, NJ:
    Bristol-Myers Squibb Company; 2020.
  14. Data on file. NIVO 462. Princeton, NJ:
    Bristol-Myers Squibb Company; 2019.
  15. Data on file. NIVO 463. Princeton, NJ:
    Bristol-Myers Squibb Company; 2019.
  16. Data on file. NIVO 369. Princeton, NJ:
    Bristol-Myers Squibb Company; 2019.
  17. Data on file. NIVO 420. Princeton, NJ:
    Bristol-Myers Squibb Company; 2019.

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