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OPDIVO(R) (nivolumab) and YERVOY(R) (ipilimumab) logos.

In the treatment of MSI-H/dMMR
unresectable or metastatic CRC

SUPERIOR PFS

vs an I‑O monotherapy 1* †

mPFS (dual primary endpoint): NR (95% CI: 53.8–NE) with OPDIVO + YERVOY vs 39.3 months (95% CI: 22.1–NE) with OPDIVO (HR=0.62 [95% CI: 0.48–0.81]; P=0.0003) 1,2

Nivolumab. 1 †Checkmate 8HW also compared OPDIVO + YERVOY with investigator’s choice chemotherapy, which included mFOLFOX6 (oxilaplatin, leucovorin, and [fluorouracil] FU) ± bevacizumab or cetuximab, or FOLFIRI (irinotecan, leucovorin, and FU) ± bevacizumab or cetuximab. PFS for OPDIVO + YERVOY vs chemotherapy in 1L patients is a dual primary endpoint. 1,2

In the treatment of MSI-H/dMMR
unresectable or metastatic CRC

SUPERIOR PFS

vs an I‑O monotherapy 1* †

mPFS (dual primary endpoint): NR (95% CI: 53.8–NE) with OPDIVO + YERVOY vs 39.3 months (95% CI: 22.1–NE) with OPDIVO (HR=0.62 [95% CI: 0.48–0.81]; P=0.0003) 1,2

Your patients with MSI-H/dMMR mCRC now have another treatment option. OPDIVO ® (nivolumab) + YERVOY ® (ipilimumab) is now FDA approved for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). 1

1L=first-line; CI=confidence interval; HR=hazard ratio; I‑O=immuno‑oncology; mCRC=metastatic colorectal cancer; mPFS=median progression‑free survival; NE=not evaluable.

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 for OPDIVO and YERVOY below, and U.S. Full Prescribing Information for OPDIVO and YERVOY .

OPDIVO + YERVOY vs OPDIVO

Superior PFS with OPDIVO + YERVOY vs an I-O monotherapy 1*

•

All patients in the trial were I-O naïve and a majority (57%) of patients in the OPDIVO + YERVOY arm were those receiving 1L treatment 1,2

Nivolumab. †The median follow-up across treatment arms was 47.0 months. 2 ‡At the 47.0-month median follow-up, sustained separation of curves was observed for up to 3 years, but these data were not powered to detect differences in the treatment effect. 2

PFS for OPDIVO + YERVOY vs chemotherapy* in patients receiving 1L treatment (dual primary endpoint) 1,3

•

mPFS: Not reached (95% CI: 38.4–NE) with OPDIVO + YERVOY (n=171) vs 5.8 mos (95% CI: 4.4–7.8) with chemotherapy (n=84); HR=0.21 (95% CI: 0.12–0.32); P<0.0001 1,3

OPDIVO + YERVOY vs OPDIVO

Similar rates of most common* Grade 3-4 ARs with OPDIVO + YERVOY vs OPDIVO monotherapy 1,4

•

Fatal adverse reactions occurred in 2 patients who received OPDIVO + YERVOY; these included myocarditis, and pneumonitis (1 each). Fatal adverse reactions occurring in 3 patients who received OPDIVO monotherapy; these included pneumonitis (n=2) and myasthenia gravis 1

•

In Checkmate 8HW, the most common adverse reactions (≥20%) in patients treated with OPDIVO + YERVOY were fatigue, diarrhea, pruritus, abdominal pain, musculoskeletal pain and nausea 1

•

No new safety signals were observed with OPDIVO + YERVOY vs OPDIVO monotherapy 2

Most common ARs are all-cause ARs which occurred in ≥10% of patients. †Includes asthenia. 5 ‡Includes body temperature increased and tumor-associated fever. 5 §Includes autoimmune colitis, colitis, enterocolitis, and immune-mediated enterocolitis. 5 ||Includes abdominal discomfort, abdominal pain lower, and abdominal pain upper. 5 ¶Includes dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis bullous, dermatitis psoriasiform, drug eruption, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, and rash vesicular. 5 #Includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, myalgia, neck pain, pain in extremity, sacral pain, and spinal pain. 5 **Includes central hypothyroidism. 5 ††Includes productive cough. 5 ‡‡Includes dyspnea exertional. 5 §§Includes iron deficiency anemia. 5

AR=adverse reaction.

Study design: Checkmate 8HW, a randomized (2:2:1), 3-arm, multicenter, open‑label phase 3 trial, studied OPDIVO 240 mg plus YERVOY 1 mg/kg q3w for a maximum of 4 doses followed by OPDIVO 480 mg q4w; OPDIVO 240 mg q2w for 6 doses followed by OPDIVO 480 mg q4w; and investigator’s choice of either mFOLFOX6 or FOLFIRI with or without bevacizumab or cetuximab in the treatment of MSI‑H/dMMR mCRC. Treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent (all arms), or a maximum treatment duration of 2 years (OPDIVO and OPDIVO + YERVOY arms only). The trial included I‑O–naïve patients with histologically confirmed unresectable or metastatic CRC, ECOG PS 0 or 1, and locally tested MSI‑H/dMMR status. Patients were stratified by prior lines of treatment (0 vs 1 vs ≥2) and primary tumor location (right vs left). The dual primary endpoints in patients with centrally confirmed MSI‑H/dMMR status were PFS by BICR for OPDIVO + YERVOY compared to the investigator’s choice chemotherapy in the first-line setting and PFS by BICR for OPDIVO + YERVOY compared to OPDIVO monotherapy across all lines.* †‡ Median follow-up for OPDIVO + YERVOY vs OPDIVO was 47.0 months, and the minimum follow-up was 16.7 months (data cutoff: 8/28/2024). Median follow-up for OPDIVO + YERVOY vs investigator’s choice chemotherapy was 31.5 months (data cutoff: 10/12/2023). 1,2

Investigator’s choice of chemotherapy could be administered until disease progression or unacceptable toxicity. 1 †All response and progression events were evaluated using RECIST v1.1. 1 ‡In patients with centrally confirmed MSI‑H/dMMR mCRC, assessed by BICR. 1

BICR=blinded independent central review; ECOG PS=Eastern Cooperative Oncology Group Performance Status; mos=months; PFS=progression-free survival; q2w=every 2 weeks; q3w=every 3 weeks; q4w=every 4 weeks.

Bring the potential PFS benefit of OPDIVO +
YERVOY to your 1L MSI-H/dMMR mCRC patients

Bring the potential PFS
benefit of OPDIVO + YERVOY
to your 1L MSI-H/dMMR
mCRC patients

INDICATION

OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC).

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 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%).

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 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 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 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 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 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 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 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 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 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 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, other transplant (including corneal graft) 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 MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, infusion-related reactions occurred in 4.2% (5/119) 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 8HW, serious adverse reactions occurred in 46% of patients receiving OPDIVO in combination with ipilimumab. The most frequent serious adverse reactions reported in ≥1% of patients who received OPDIVO with ipilimumab were adrenal insufficiency (2.8%), hypophysitis (2.8%), diarrhea (2.0%), abdominal pain (2.0%), small intestinal obstruction (2.0%), pneumonia (1.7%), acute kidney injury (1.4%), immune mediated enterocolitis (1.4%), pneumonitis (1.4%), colitis (1.1%), large intestinal obstruction (1.1%), and urinary tract infection (1.1%). Fatal adverse reactions occurred in 2 (0.6%) patients who received OPDIVO in combination with ipilimumab; these included myocarditis and pneumonitis (1 each).

Common Adverse Reactions

In Checkmate 8HW, the most common adverse reactions reported in ≥20% of patients treated with OPDIVO in combination with ipilimumab were fatigue, diarrhea, pruritus, abdominal pain, musculoskeletal pain, and nausea.

Please see US Full Prescribing Information for OPDIVO and YERVOY.

References:

OPDIVO [package insert]. Princeton, NJ: Bristol‑Myers Squibb Company.

André T, Elez E, Lenz H‑J, et al. Nivolumab plus ipilimumab versus nivolumab in microsatellite instability‑high metastatic colorectal cancer (CheckMate 8HW): a randomised, open‑label, phase 3 trial. Lancet . 2025;405(10476):383-395.

Andre T, Elez E, Lenz H-J, et al. First results of nivolumab plus ipilimumab vs nivolumab monotherapy for microsatellite instability high/mismatch repair-deficient metastatic colorectal cancer from CheckMate 8HW. Oral presentation at ASCO GI 2025. Abstract LBA143.

Data on file. BMS-NIVO-0343. Princeton, NJ: Bristol-Myers Squibb Company. 2025.

Data on file. BMS-NIVO-0344. Princeton, NJ: Bristol-Myers Squibb Company. 2025.

Bristol Myers Squibb is committed to transparency. For information on the list price of OPDIVO and OPDIVO combination indications as well as information regarding average out-of-pocket costs and assistance programs, please visit our pricing information page .

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OPDIVO ®, YERVOY ® , and the related logos are registered trademarks of Bristol‑Myers Squibb Company.

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