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Contact us at 1-855-OPDIVO-1

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Indications

Calendar With Canoe Calendar With Canoe

Only* OPDIVO® (nivolumab)
+ YERVOY® (ipilimumab)
offers dual I-O durability

Delivering a chance for long-term
survival1

*This only applies to approved indications 1L
mMelanoma, 1L intermediate/poor-risk aRCC, and 1L mNSCLC
in patients who express PD-L1 (≥1%).1
1L=first line; aRCC=advanced renal cell carcinoma;
I-O=immuno-oncology; mMelanoma=unresectable or metastatic melanoma; mNSCLC=metastatic non-small cell lung cancer; PD-L1=programmed death ligand 1.

Please select a tab and scroll down to explore efficacy and relevant data below.

1L Metastatic Non-Small Cell Lung Cancer
in Checkmate 2271

For previously untreated patients with metastatic NSCLC whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations1

In the Checkmate 227 (mNSCLC), in patients with PD-L1 expression ≥1% with a median follow-up of 54.8 months, the 4-year OS rate for OPDIVO + YERVOY was 29% vs 18% for chemotherapy. Primary analysis at 29.3 months minimum follow up: mOS was 17.1 months with OPDIVO + YERVOY vs 14.9 months with chemotherapy. HR=0.79 (95% CI: 0.67–0.94); P=0.0066.1-3

Checkmate 227 Study Information1,3

Checkmate 227 was a randomized, open-label phase 3 trial in patients with metastatic or recurrent NSCLC. Part 1a of the study included patients (18 years of age or older) with histologically confirmed Stage IV or recurrent NSCLC, ECOG performance status 0 or 1, no prior anticancer therapy, and had PD-L1 expression ≥1%. Patients with known EGFR mutations or ALK translocations sensitive to available targeted inhibitor therapy, untreated brain metastases, carcinomatous meningitis, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded. Patients with PD-L1 tumor expression ≥1% were randomized to OPDIVO 3 mg/kg q2w + YERVOY 1 mg/kg q6w (n=396) or platinum-doublet chemotherapy (n=397). Tumor specimens were evaluated prospectively using the PD-L1 IHC 28-8 pharmDx assay at a central laboratory. The primary endpoint in Part 1a was OS in patients with PD-L1 ≥1%. The pre-specified descriptive efficacy outcome measures included PFS. Treatment continued until disease progression, unacceptable toxicity, or for up to 2 years.1,3

In Checkmate 227, patients in the comparator arm received up to 4 cycles of platinum-doublet chemo q3w; NSQ: pemetrexed + carboplatin or cisplatin, with optional pemetrexed maintenance following chemo; SQ: gemcitabine + carboplatin or cisplatin.1,3
The recommended dose of OPDIVO in combination with YERVOY is 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 6 weeks, until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression. 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 every 4 weeks, respectively, until disease progression or unacceptable toxicity.1
More than 4 years of follow-up analysis in Checkmate 227 (mNSCLC) of follow-up analysis in Checkmate 227 (mNSCLC)
more than4 years

Select Important Safety Information

Summary of Warnings and Precautions

OPDIVO and YERVOY are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when OPDIVO is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.

Please see additional Important Safety Information below.

Overall survival for PD-L1 ≥1% (extended follow-up analysis)1-3

Overall survival for PD-L1≥1%

Median follow-up of 54.8 months2

  • Median OS at primary analysis (minimum follow-up of 29.3 months) in patients with tumor PD-L1 expression ≥1%1,3
    • OPDIVO + YERVOY: 17.1 months (n=396 [95% Cl: 15.0–20.1])
    • Chemotherapy: 14.9 months (n=397 [95% Cl: 12.7–16.7])
    • HR=0.79 (95% CI: 0.67–0.94; P=0.0066)
  • Median PFS with a median follow-up of 54.8 months: 5.1 months (95% CI: 4.1–6.3) with OPDIVO + YERVOY and 5.6 months (95% CI: 4.6–5.8) with chemo alone; HR=0.81; 95% CI: 0.68–0.961,2
    • In Checkmate 227 Part 1a, PFS, ORR, and DOR were pre-specified descriptive analyses. The primary efficacy outcome measure was OS1
  • 29% of patients enrolled had SQ disease; 71% had NSQ disease1
CI=confidence interval; DOR=duration of response; ECOG=Eastern Cooperative Oncology Group; HR=hazard ratio; IHC-immunohistochemistry; IV=intravenous; mOS=median overall survival; NSQ=non-squamous cell; ORR=overall response rate; OS=overall survival; PFS-progression-free survival; q2w=every 2 weeks; q3w=every 3 weeks; q6w=every 6 weeks; SQ=squamous.

Select Important Safety Information

Serious Adverse Reactions

In Checkmate 227, serious adverse reactions occurred in 58% of patients (n=576). The most frequent (≥2%) serious adverse reactions were pneumonia, diarrhea/colitis, pneumonitis, hepatitis, pulmonary embolism, adrenal insufficiency, and hypophysitis. Fatal adverse reactions occurred in 1.7% of patients; these included events of pneumonitis (4 patients), myocarditis, acute kidney injury, shock, hyperglycemia, multi-system organ failure, and renal failure.

Common Adverse Reactions

In Checkmate 227, the most common (≥20%) adverse reactions were fatigue (44%), rash (34%), decreased appetite (31%), musculoskeletal pain (27%), diarrhea/colitis (26%), dyspnea (26%), cough (23%), hepatitis (21%), nausea (21%), and pruritus (21%).

Please see additional Important Safety Information below.

Metastatic Melanoma in Checkmate 067

For patients with unresectable or metastatic melanoma1

In the Checkmate 067 (mMelanoma) follow-up analysis at ~6.5 years, OS for OPDIVO + YERVOY was 49% vs 23% for YERVOY. mOS was reached at 72.1 months for OPDIVO + YERVOY vs 19.9 months with YERVOY. Primary analysis at 28 months: HR+ 0.55 (95% CI: 0.44–0.69); P<0.0001.1,4

Checkmate 067 Study Information1

OPDIVO + YERVOY was evaluated in a double-blind, randomized study of previously untreated, unresectable, or metastatic melanoma. Patients were randomized (1:1:1) to receive OPDIVO + YERVOY (OPDIVO 1 mg/kg and YERVOY 3 mg/kg q3w for 4 doses, followed by OPDIVO monotherapy 3 mg/kg q2w§), or OPDIVO 3 mg/kg q2w, or YERVOY 3 mg/kg q3w for 4 doses plus placebo. Major efficacy outcome measures were investigator-assessed PFS and OS. Additional efficacy outcome measures were confirmed ORR and DOR.1

§The recommended dose of OPDIVO is 1 mg/kg administered as an IV infusion over 30 minutes, followed by YERVOY 3 mg/kg administered as an IV infusion over 90 minutes on the same day, q3w for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of the combination, administer OPDIVO as a single agent, either 240 mg q2w or 480 mg q4w, as an IV infusion over 30 minutes until disease progression or unacceptable toxicity.1
6.5 years of follow-up analysis in Checkmate 067 (mMelanoma) calendar
~6.5 years

Select Important Safety Information

Summary of Warnings and Precautions

OPDIVO and YERVOY are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when OPDIVO is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.

Please see additional Important Safety Information below.

A chance for durable survival with 49% of ITT patients alive at ~6.5 years4,5

Overall survival in the ITT population through ~6.5 years

OPDIVO + YERVOY median overall survival (mOS) was reached after 6 years of follow-up4

mOS at ~6.5 years (95% CI, months):

  • OPDIVO + YERVOY: 72.1 (38.2–NR)
  • OPDIVO: 36.9 (28.2–58.7)
  • YERVOY: 19.9 (16.8–24.6)

This study was not designed to compare OPDVIO + YERVOY with OPDIVO.

CI=confidence interval; DOR=duration of response; HR=hazard ratio; ITT=intention to treat; mOS=median overall survival; NR=not reached; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; q2w=every 2 weeks; q3w=every 3 weeks; q4w=every 4 weeks.

Select Important Safety Information

Serious Adverse Reactions

In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.2%), colitis (10% and 1.9%) and pyrexia (10% and 1.0%).

Common Adverse Reactions

In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%).

Please see additional Important Safety Information below.

1L Advanced Renal Cell Carcinoma
in Checkmate 214

For previously untreated patients with intermediate or poor-risk advanced renal cell carcinoma1

Overall survival data in Checkmate 214

  • In the Checkmate 214 (aRCC) extended follow-up analysis at 48 months, the mOS was 48.1 months for OPDIVO + YERVOY (95% CI: 35.6–NE) vs 26.6 months for sunitinib (95% CI: 22.1–33.5), HR=0.65 (95% CI: 0.54-0.78). The 48-month OS rate for OPDIVO + YERVOY was 50% vs 35.8% for sunitinib. The mOS at primary analysis (median follow-up time of 25.2 months) for OPDIVO + YERVOY was not yet reached (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<0.0001.1,6,7

Overall response rate|| in Checkmate 214

  • Overall response rate at primary analysis (median follow-up of 25.2 months) was 41.6% (n=177/425 [95% CI: 36.9–46.5]); CR: 9.4% [n=40]; PR: 32.2% [n=137] for OPDIVO + YERVOY vs 26.5% (n=112/422 [95% CI: 22.4–31.0]); CR: 1.2% [n=5]; PR: 25.4% [n=107] for sunitinib (P<0.0001)1,7

Progression-free survival|| in Checkmate 214

  • Progression-free survival at primary analysis (median follow-up of 25.2 months) for OPDIVO + YERVOY and sunitinib was 11.6 months (95% CI: 8.7–15.5) vs 8.4 months (95% CI: 7.0–10.8), respectively, HR=0.82 (99.1% CI: 0.64–1.05). Per a pre-specified analysis, PFS did not meet statistical significance1,7

Checkmate 214 Study Information1,7

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.1,7||

||Assessed by an independent radiographic review committee per RECIST v1.1.7
The recommended dose of OPDIVO in combination with YERVOY is 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 every 4 weeks, respectively, until disease progression or unacceptable toxicity.1
4 years of  follow-up analysis in Checkmate 214 (aRCC) calendar
4 years

Select Important Safety Information

Summary of Warnings and Precautions

OPDIVO and YERVOY are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when OPDIVO is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.

Please see additional Important Safety Information below.

Overall survival in intermediate or poor-risk patients1,6,7

Overall survival for PD-L1  ≥1% (extended follow-up analysis)
  • mOS at primary analysis (median follow-up time of 25.2 months): Median OS was 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<0.00011,7
  • In the primary analysis (median follow-up time of 25.2 months), the pre-specified 12-month overall survival rate was 80% (95% CI: 76–84) with OPDIVO + YERVOY vs 72% (95% CI: 67–76) with sunitinib7
  • The 48-month overall survival rate analysis was not pre-specified within the study protocol7
  • mOS at extended follow-up (minimum follow-up time of 48 months) was 48.1 months (95% CI: 35.6–NE) for OPDIVO + YERVOY vs 26.6 months for sunitinib (95% CI: 22.1–33.5), HR=0.65 (95% CI: 0.54–0.78)6
  • The 48-month OS rate for OPDIVO + YERVOY was 50% vs 35.8% for sunitinib
CI=confidence interval; CR=complete response; HR-hazard ratio; IMDC=International Metastatic RCC Database Consortium; IV=intravenous; mOS=median overall survival; NE=not estimable; OS=overall survival; ORR=overall response rate; PFS=progression-free survival, PR=partial response.

Select Important Safety Information

Serious Adverse Reactions

Serious adverse reactions occurred in 59% of patients receiving OPDIVO + YERVOY. The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDVIO + YERVOY were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis; for sunitinib they were pneumonia, pleural effusion, and dyspnea.

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%).

Please see additional Important Safety Information below.

1L Metastatic
Non-Small Cell Lung Cancer in Checkmate 2271

For previously untreated patients with metastatic NSCLC whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations1

More than 4 years of follow-up analysis in Checkmate 227 (mNSCLC) of follow-up analysis in Checkmate 227 (mNSCLC)
more than4 years

In the Checkmate 227 (mNSCLC), in patients with PD-L1 expression ≥1% with a median follow-up of 54.8 months, the 4-year OS rate for OPDIVO + YERVOY was 29% vs 18% for chemotherapy. Primary analysis at 29.3 months minimum follow up: mOS was 17.1 months with OPDIVO + YERVOY vs 14.9 months with chemotherapy. HR=0.79 (95% CI: 0.67–0.94); P=0.0066.1-3

Select Important Safety Information

Summary of Warnings and Precautions

OPDIVO and YERVOY are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when OPDIVO is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.

Please see additional Important Safety Information below.

Checkmate 227 Study Information1,3

Checkmate 227 was a randomized, open-label phase 3 trial in patients with metastatic or recurrent NSCLC. Part 1a of the study included patients (18 years of age or older) with histologically confirmed Stage IV or recurrent NSCLC, ECOG performance status 0 or 1, no prior anticancer therapy, and had PD-L1 expression ≥1%. Patients with known EGFR mutations or ALK translocations sensitive to available targeted inhibitor therapy, untreated brain metastases, carcinomatous meningitis, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded. Patients with PD-L1 tumor expression ≥1% were randomized to OPDIVO 3 mg/kg q2w + YERVOY 1 mg/kg q6w (n=396) or platinum-doublet chemotherapy (n=397). Tumor specimens were evaluated prospectively using the PD-L1 IHC 28-8 pharmDx assay at a central laboratory. The primary endpoint in Part 1a was OS in patients with PD-L1 ≥1%. The pre-specified descriptive efficacy outcome measures included PFS. Treatment continued until disease progression, unacceptable toxicity, or for up to 2 years.1,3

In Checkmate 227, patients in the comparator arm received up to 4 cycles of platinum-doublet chemo q3w; NSQ: pemetrexed + carboplatin or cisplatin, with optional pemetrexed maintenance following chemo; SQ: gemcitabine + carboplatin or cisplatin.1,3
The recommended dose of OPDIVO in combination with YERVOY is 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 6 weeks, until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression. 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 every 4 weeks, respectively, until disease progression or unacceptable toxicity.1

Overall survival for PD-L1 ≥1% (extended follow-up analysis)1-3

Overall survival for PD-L1  ≥1% (extended follow-up analysis)

Median follow-up of 54.8 months2

  • Median OS at primary analysis (minimum follow-up of 29.3 months) in patients with tumor PD-L1 expression ≥1%1,3
    • OPDIVO + YERVOY: 17.1 months (n=396 [95% Cl: 15.0–20.1])
    • Chemotherapy: 14.9 months (n=397 [95% Cl: 12.7–16.7])
    • HR=0.79 (95% CI: 0.67–0.94; P=0.0066)
  • Median PFS with a median follow-up of 54.8 months: 5.1 months (95% CI: 4.1–6.3) with OPDIVO + YERVOY and 5.6 months (95% CI: 4.6–5.8) with chemo alone; HR=0.81; 95% CI: 0.68–0.961,2
    • In Checkmate 227 Part 1a, PFS, ORR, and DOR were pre-specified descriptive analyses. The primary efficacy outcome measure was OS1
  • 29% of patients enrolled had SQ disease; 71% had NSQ disease1
CI=confidence interval; DOR=duration of response; ECOG=Eastern Cooperative Oncology Group; HR=hazard ratio; IHC-immunohistochemistry; IV=intravenous; mOS=median overall survival; NSQ=non-squamous cell; ORR=overall response rate; OS=overall survival; PFS-progression-free survival; q2w=every 2 weeks; q3w=every 3 weeks; q6w=every 6 weeks; SQ=squamous.

Select Important Safety Information

Serious Adverse Reactions

In Checkmate 227, serious adverse reactions occurred in 58% of patients (n=576). The most frequent (≥2%) serious adverse reactions were pneumonia, diarrhea/colitis, pneumonitis, hepatitis, pulmonary embolism, adrenal insufficiency, and hypophysitis. Fatal adverse reactions occurred in 1.7% of patients; these included events of pneumonitis (4 patients), myocarditis, acute kidney injury, shock, hyperglycemia, multi-system organ failure, and renal failure.

Common Adverse Reactions

In Checkmate 227, the most common (≥20%) adverse reactions were fatigue (44%), rash (34%), decreased appetite (31%), musculoskeletal pain (27%), diarrhea/colitis (26%), dyspnea (26%), cough (23%), hepatitis (21%), nausea (21%), and pruritus (21%).

Please see additional Important Safety Information below.

Metastatic Melanoma in Checkmate 067

For patients with unresectable or metastatic melanoma1

6.5 years of follow-up analysis in Checkmate 067 (mMelanoma) calendar
~6.5 years

In the Checkmate 067 (mMelanoma) follow-up analysis at ~6.5 years, OS for OPDIVO + YERVOY was 49% vs 23% for YERVOY. mOS was reached at 72.1 months for OPDIVO + YERVOY vs 19.9 months with YERVOY. Primary analysis at 28 months: HR+ 0.55 (95% CI: 0.44–0.69); P<0.0001.1,4

Select Important Safety Information

Summary of Warnings and Precautions

OPDIVO and YERVOY are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when OPDIVO is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.

Please see additional Important Safety Information below.

Checkmate 067 Study Information1

OPDIVO + YERVOY was evaluated in a double-blind, randomized study of previously untreated, unresectable, or metastatic melanoma. Patients were randomized (1:1:1) to receive OPDIVO + YERVOY (OPDIVO 1 mg/kg and YERVOY 3 mg/kg q3w for 4 doses, followed by OPDIVO monotherapy 3 mg/kg q2w§), or OPDIVO 3 mg/kg q2w, or YERVOY 3 mg/kg q3w for 4 doses plus placebo. Major efficacy outcome measures were investigator-assessed PFS and OS. Additional efficacy outcome measures were confirmed ORR and DOR.1

§The recommended dose of OPDIVO is 1 mg/kg administered as an IV infusion over 30 minutes, followed by YERVOY 3 mg/kg administered as an IV infusion over 90 minutes on the same day, q3w for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of the combination, administer OPDIVO as a single agent, either 240 mg q2w or 480 mg q4w, as an IV infusion over 30 minutes until disease progression or unacceptable toxicity.1

A chance for durable survival with 49% of ITT patients alive at ~6.5 years4,5

Overall survival in the ITT population through ~6.5 years

OPDIVO + YERVOY median overall survival (mOS) was reached after 6 years of follow-up4

mOS at ~6.5 years (95% CI, months):

  • OPDIVO + YERVOY: 72.1 (38.2–NR)
  • OPDIVO: 36.9 (28.2–58.7)
  • YERVOY: 19.9 (16.8–24.6)

This study was not designed to compare OPDIVO + YERVOY with OPDIVO.

CI=confidence interval; DOR=duration of response; HR=hazard ratio; ITT=intention to treat; mOS=median overall survival; NR=not reached; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; q2w=every 2 weeks; q3w=every 3 weeks; q4w=every 4 weeks.

Select Important Safety Information

Serious Adverse Reactions

In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.2%), colitis (10% and 1.9%) and pyrexia (10% and 1.0%).

Common Adverse Reactions

In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%).

Please see additional Important Safety Information below.

1L Advanced Renal Cell Carcinoma in Checkmate 214

For previously untreated patients with intermediate or poor-risk advanced renal cell carcinoma1

4 years of  follow-up analysis in Checkmate 214 (aRCC) calendar
4 years

Overall survival data in Checkmate 214

  • In the Checkmate 214 (aRCC) extended follow-up analysis at 48 months, the mOS was 48.1 months for OPDIVO + YERVOY (95% CI: 35.6–NE) vs 26.6 months for sunitinib (95% CI: 22.1–33.5), HR=0.65 (95% CI: 0.54-0.78). The 48-month OS rate for OPDIVO + YERVOY was 50% vs 35.8% for sunitinib. The mOS at primary analysis (median follow-up time of 25.2 months) for OPDIVO + YERVOY was not yet reached (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<0.0001.1,6,7

Overall response rate|| in Checkmate 214

  • Overall response rate at primary analysis (median follow-up of 25.2 months) was 41.6% (n=177/425 [95% CI: 36.9–46.5]); CR: 9.4% [n=40]; PR: 32.2% [n=137] for OPDIVO + YERVOY vs 26.5% (n=112/422 [95% CI: 22.4–31.0]); CR: 1.2% [n=5]; PR: 25.4% [n=107] for sunitinib (P<0.0001)1,7

Progression-free survival|| in Checkmate 214

  • Progression-free survival at primary analysis (median follow-up of 25.2 months) for OPDIVO + YERVOY and sunitinib was 11.6 months (95% CI: 8.7–15.5) vs 8.4 months (95% CI: 7.0–10.8), respectively, HR=0.82 (99.1% CI: 0.64–1.05). Per a pre-specified analysis, PFS did not meet statistical significance1,7

Select Important Safety Information

Summary of Warnings and Precautions

OPDIVO and YERVOY are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when OPDIVO is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.

Please see additional Important Safety Information below.

Checkmate 214 Study Information1,7

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.1,7||

||Assessed by an independent radiographic review committee per RECIST v1.1.7
The recommended dose of OPDIVO in combination with YERVOY is 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 every 4 weeks, respectively, until disease progression or unacceptable toxicity.1

Overall survival in intermediate or poor-risk patients1,6,7

  • mOS at primary analysis (median follow-up time of 25.2 months): Median OS was 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<0.00011,7
  • In the primary analysis (median follow-up time of 25.2 months), the pre-specified 12-month overall survival rate was 80% (95% CI: 76–84) with OPDIVO + YERVOY vs 72% (95% CI: 67–76) with sunitinib7
  • The 48-month overall survival rate analysis was not pre-specified within the study protocol7
  • mOS at extended follow-up (minimum follow-up time of 48 months) was 48.1 months (95% CI: 35.6–NE) for OPDIVO + YERVOY vs 26.6 months for sunitinib (95% CI: 22.1–33.5), HR=0.65 (95% CI: 0.54–0.78)6
  • The 48-month OS rate for OPDIVO + YERVOY was 50% vs 35.8% for sunitinib
CI=confidence interval; CR=complete response; HR-hazard ratio; IMDC=International Metastatic RCC Database Consortium; IV=intravenous; mOS=median overall survival; NE=not estimable; OS=overall survival; ORR=overall response rate; PFS=progression-free survival, PR=partial response.

Select Important Safety Information

Serious Adverse Reactions

Serious adverse reactions occurred in 59% of patients receiving OPDIVO + YERVOY. The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDVIO + YERVOY were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis; for sunitinib they were pneumonia, pleural effusion, and dyspnea.

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%).

Please see additional Important Safety Information below.

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FULL INDICATIONS

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 3.9% (26/666) of patients, including Grade 3 (1.4%) and Grade 2 (2.6%). In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune-mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%). Four patients (0.7%) died due to pneumonitis.

Immune-Mediated Colitis

OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. 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. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated colitis occurred in 9% (60/666) of patients, including Grade 3 (4.4%) and Grade 2 (3.7%).

Immune-Mediated Hepatitis and Hepatotoxicity

OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), Grade 3 (4.9%), and Grade 2 (0.4%).

Immune-Mediated Endocrinopathies

OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, adrenal insufficiency occurred in 7% (48/666) of patients, including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%).

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4% (29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and Grade 2 (0.9%).

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, thyroiditis occurred in 2.7% (22/666) of patients, including Grade 3 (4.5%) and Grade 2 (2.2%).

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hyperthyroidism occurred in 12% (80/666) of patients, including Grade 3 (0.6%) and Grade 2 (4.5%).

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypothyroidism occurred in 18% (122/666) of patients, including Grade 3 (0.6%) and Grade 2 (11%).

In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%), and Grade 2 (0.9%).

Immune-Mediated Nephritis with Renal Dysfunction

OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated nephritis with renal dysfunction occurred in 4.1% (27/666) of patients, including Grade 4 (0.6%), Grade 3 (1.1%), and Grade 2 (2.2%).

Immune-Mediated Dermatologic Adverse Reactions

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456) of patients, including Grade 3 (4.8%) and Grade 2 (10%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated rash occurred in 16% (108/666) of patients, including Grade 3 (3.5%) and Grade 2 (4.2%).

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO monotherapy or OPDIVO in combination with YERVOY or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine: hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1% of patients unless otherwise specified: nervous system: autoimmune neuropathy (2%), myasthenic syndrome/myasthenia gravis, motor dysfunction; cardiovascular: angiopathy, temporal arteritis; ocular: blepharitis, episcleritis, orbital myositis, scleritis; gastrointestinal: pancreatitis (1.3%); other (hematologic/immune): conjunctivitis, cytopenias (2.5%), eosinophilia (2.1%), erythema multiforme, hypersensitivity vasculitis, neurosensory hypoacusis, psoriasis.

Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. 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 YERVOY, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

OPDIVO and YERVOY can cause severe infusion-related reactions. Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions. 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 melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related reactions occurred in 5.1% (28/547) of patients.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO or YERVOY. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between OPDIVO or YERVOY and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO and YERVOY prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal studies, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and 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 randomized 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

There are no data on the presence of OPDIVO or YERVOY in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 5 months after the last dose.

Serious Adverse Reactions

In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.2%), colitis (10% and 1.9%), and pyrexia (10% and 1.0%). In Checkmate 227, serious adverse reactions occurred in 58% of patients (n=576). The most frequent (≥2%) serious adverse reactions were pneumonia, diarrhea/colitis, pneumonitis, hepatitis, pulmonary embolism, adrenal insufficiency, and hypophysitis. Fatal adverse reactions occurred in 1.7% of patients; these included events of pneumonitis (4 patients), myocarditis, acute kidney injury, shock, hyperglycemia, multi-system organ failure, and renal failure. 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.

Common Adverse Reactions

In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%). In Checkmate 227, the most common (≥20%) adverse reactions were fatigue (44%), rash (34%), decreased appetite (31%), musculoskeletal pain (27%), diarrhea/colitis (26%), dyspnea (26%), cough (23%), hepatitis (21%), nausea (21%), and pruritus (21%). 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 US Full Prescribing Information for OPDIVO and YERVOY.

Clinical Trials and Patient Populations

Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY.

References

  1. OPDIVO [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2021.
  2. Paz-Ares LG, Ciuleanu TE, Lee JS, et al. Nivolumab + ipilimumab vs chemotherapy as first-line treatment for advanced non-small cell lung cancer: 4-year update from CheckMate 227. Oral presentation at ASCO 2021. Abstract 9016.
  3. Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019;381(21):2020-2031.
  4. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. CheckMate 067: 6.5-year outcomes in patients with advanced melanoma. Presentation at: ASCO 2021; June 4-8; Virtual. Abstract 9506.
  5. Data on file. EBD 2630. Princeton, NJ: Bristol-Myers Squibb Company; 2021.
  6. Albiges L, Tannir NM, Burotto M, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma in CheckMate 214: 4-year follow-up and subgroup analysis of patients without nephrectomy. Poster presentation at ESMO 2020. Abstract 711P.
  7. Motzer RJ, Tannir NM, McDermott DF, et al; for the Checkmate 214 Investigators. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277-1290.