First-Line Non-Small Cell Lung Cancer: Overall Survival with Dual Immunotherapy-Based Treatment

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Sponsored by Bristol Myers Squibb

Historically, metastatic non-small cell lung cancer (mNSCLC) has been a complex disease and research has pursued new approaches to give more patients the chance at a longer life.1.2 Fortunately, this research has ushered in a number of advances, including the development of dual immunotherapy-based treatment options.3

In 2020, the U.S. Food and Drug Administration (FDA) approved two dual immunotherapy approaches to treat metastatic NSCLC. The first was
Opdivo ® (nivolumab) + Yervoy ®(ipilimumab), which is for the first-line treatment of patients with metastatic NSCLC whose tumors express PD-L1 ≥1% (as determined by an FDA-approved test) without EGFR or ALK genomic tumor aberrations.3 This approval was supported by data from Part 1a of a Phase 3 trial, CheckMate -227.3 Soon after, the FDA approved Opdivo + Yervoy combined with two cycles of chemotherapy for the first-line treatment of metastatic or recurrent NSCLC without EGFR or ALK genomic tumor aberrations, which was supported by another Phase 3 trial, CheckMate -9LA.3

“Metastatic lung cancer has always been challenging to treat and treatment options for patients have historically been limited,” said Steven L. McCune, M.D., Ph.D., Northwest Georgia Oncology Centers.1,2 “Thankfully, advances in research have brought about additional treatment options and we continue to analyze follow-up data to understand the impact of these treatments over time. The approvals of Opdivo plus Yervoy-based combinations were an important step forward for the treatment of the disease and further expanded the available options for many patients.”3,4,5

Follow-up analyses of overall survival data from CheckMate -227 (four-year data) and CheckMate -9LA (two-year data) were presented at the virtual American Society of Clinical Oncology (ASCO) annual meeting 2021, making the CheckMate -227 analysis the longest median follow-up to date from any Phase 3 study for any approved dual immunotherapy in metastatic NSCLC.4,5

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.3 Please see the Important Safety Information section below.

Data from CheckMate -227 Part 1a Show a Chance for Long-Term, Durable Survival Versus Chemo at Four Years

The CheckMate -227 trial evaluated Opdivo + Yervoy versus platinum-doublet chemotherapy in patients with first-line metastatic NSCLC across non-squamous and squamous tumor histologies.3 In Part 1a of the trial, 396 patients with PD-L1 expression ≥1% received Opdivo + Yervoy versus 397 patients who received chemotherapy.3 The primary efficacy outcome measure was overall survival (OS) and additional pre-specified descriptive efficacy outcome measures included progression-free survival (PFS), overall response rate (ORR) and duration of response as assessed by Blinded Independent Central Review (BICR).3

All patients had Stage IV or recurrent NSCLC, received no prior systemic therapy, had no known sensitizing EGFR/ALK alterations and an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 in addition to a PD-L1 expression ≥1%.3 Patients with untreated brain metastases, carcinomatous meningitis, active autoimmune disease or medical conditions requiring systemic immunosuppression were excluded.3

Patients in the combination group (n=396) received Opdivo 3mg/kg every two weeks (Q2W) plus Yervoy 1mg/kg every six weeks (Q6W).3 Patients in the chemotherapy group (n=397) received up to four cycles of platinum-doublet chemotherapy every three weeks (Q3W) with optional pemetrexed maintenance following chemotherapy. Patients were treated until disease progression or unacceptable toxicity, or up to 24 months.3

In the primary analysis of Part 1a (minimum follow-up of 29.3 months), Opdivo + Yervoy demonstrated superior OS versus chemotherapy (hazard ratio [HR] 0.79; 95% Confidence Interval [CI]: 0.67 to 0.94; P=0.0066), with a median OS of 17.1 (95% CI: 15 to 20.1) versus
14.9 months (95% CI: 12.7 to 16.7).3,6 At three years (median follow-up 43.1 months), 33% of patients treated with Opdivo + Yervoy were still alive and 22% with chemotherapy.7 At four years (median follow-up 54.8 months), 29% of patients treated with Opdivo + Yervoy were still alive and 18% with chemotherapy, showing the durable, long-term survival potential of this treatment option.4

Additionally, at the four-year follow-up analysis, the BICR-assessed ORR was 36% (144/396; 95% CI: 32 to 41) with Opdivo + Yervoy and
30% (120/397; 95% CI: 26 to 35) with chemotherapy.3

Among patients who responded to Opdivo + Yervoy, 38% and 34% remained in response at three and four years, respectively, versus 10% and 7% with chemotherapy.

CheckMate -227: In a Cross-Histology Trial for Patients with mNSCLC (PD-L1 >1%)

CheckMate -227: OS for PD-L1 ≥1% (Extended Follow-Up Analysis)

Select Safety Profile & Adverse Events Observed

In CheckMate -227, serious adverse reactions occurred in 58% of patients.3 Opdivo + Yervoy was discontinued for adverse reactions in 24% of patients and 53% had at least one dose withheld for an adverse reaction.3 The most frequent (≥2%) serious adverse reactions were pneumonia, diarrhea/colitis, pneumonitis, hepatitis, pulmonary embolism, adrenal insufficiency and hypophysitis.3 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.3

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%).3

With a median follow-up of 54.8 months, no new safety signals were observed with Opdivo + Yervoy.4

Data from CheckMate -9LA Show Durable Survival with Opdivo + Yervoy + Chemotherapy Versus Chemotherapy for Patients at Two Years

The CheckMate -9LA trial evaluated Opdivo + Yervoy in combination with chemotherapy versus chemotherapy alone in patients with first-line metastatic NSCLC .3 In the trial, 361 patients were treated with Opdivo + Yervoy in combination with a platinum-doublet chemotherapy versus 358 patients who received chemotherapy for four cycles and optional pemetrexed maintenance for non-squamous patients (if eligible).3 The primary efficacy outcome measure was OS and additional efficacy outcome measures included progression-free survival (PFS), overall response rate (ORR) and duration of response.3

All patients had Stage IV or recurrent NSCLC, had received no prior systemic therapy, had no known sensitizing EGFR/ALK alterations and an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.3 Patients with untreated brain metastases, carcinomatous meningitis, active autoimmune disease or medical conditions requiring systemic immunosuppression were excluded.3

Patients in the combination group (n=361) received Opdivo 360 mg every three weeks (Q3W) and Yervoy 1mg/kg every six weeks (Q6W) plus two cycles of platinum-doublet chemotherapy. Treatment with Opdivo + Yervoy continued until disease progression, unacceptable toxicity or up to two years. Patients in the chemotherapy group (n=358) received four cycles of platinum-doublet chemotherapy.3

In the initial pre-specified interim analysis (minimum follow-up 8.1 months), Opdivo + Yervoy combined with two cycles of platinum-doublet chemotherapy demonstrated superior OS versus chemotherapy (HR 0.69; 96.71% CI: 0.55 to 0.87; P=0.0006).3 Median OS (mOS) was
14.1 months (95% CI: 13.2 to 16.2) versus 10.7 months (95% CI: 9.5 to 12.5), respectively.3

At two years (with a minimum follow-up of 24.4 months), 38% of patients who received Opdivo + Yervoy with two cycles of chemotherapy were alive, compared to 26% of those who received chemotherapy alone, with a mOS of 15.8 months with the dual immunotherapy combination plus chemotherapy and 11.0 months with chemotherapy alone (HR 0.72, 95% CI: 0.61 to 0.86).5

CheckMate -9LA: OS (Extended Follow-Up Analysis)

With extended follow-up, the overall survival seen with Opdivo + Yervoy combined with two cycles of chemotherapy was consistent in patients with PD-L1 expression <1% and ≥1%.5

In an exploratory analysis, patients with PD-L1 <1% who were treated with Opdivo + Yervoy and two cycles of chemotherapy (n=135) had a mOS of 17.7 months (95% CI: 13.7 to 20.3) and 9.8 months for chemotherapy alone (n=128) (95% CI: 7.7 to 13.5), with a HR of 0.67 (95% CI: 0.51 to 0.88).5 For patients with PD-L1≥1%, the mOS for those treated with the combination (n=204) was 15.8 months (95% CI: 13.8 to 22.2) and 10.9 months for chemotherapy alone (n=204) (95% CI: 9.5 to 13.2), with a HR of 0.70 (95% CI: 0.56 to 0.89).5 CheckMate -9LA was not powered to detect differences in the treatment effect in PD-L1 subgroups; therefore, results from this exploratory analysis should be interpreted with caution because of the limited patient numbers and potential imbalances in baseline characteristics within the subgroup.

At two years (with a minimum follow-up of 24.4 months), 37% of patients with PD-L1<1% who were treated with Opdivo + Yervoy and two cycles of chemotherapy were alive, compared to 22% of those who received chemotherapy alone.5 For patients with PD-L1 ≥1%, 41% who were treated with Opdivo + Yervoy and two cycles of chemotherapy were alive, compared to 28% of those who received chemotherapy alone.5

Select Safety Profile & Adverse Events Observed

In CheckMate -9LA, serious adverse reactions occurred in 57% of patients.3 Opdivo + Yervoy in combination with platinum-doublet chemotherapy were discontinued for adverse reactions in 24% of patients and 56% had at least one treatment withheld for an adverse reaction.3 The most frequent (>2%) serious adverse reactions were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis and respiratory failure.3 Fatal adverse reactions occurred in 7 (2%) patients, and included hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia and massive hemoptysis in the setting of thrombocytopenia.3

The most common (>20%) adverse reactions were fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%), rash (30%),
decreased appetite (28%), constipation (21%) and pruritus (21%).3

With a minimum follow-up of 24.4 months, no new safety signals were observed with Opdivo + Yervoy in combination with chemotherapy.5

“These follow-up data from CheckMate -227 Part 1a and CheckMate -9LA, which show the potential for durable survival with Opdivo plus Yervoy-based combinations, demonstrate how far we have come in treating advanced forms of this often devastating disease,” said Dr. McCune.4,5

For more information about Opdivo + Yervoy, please visit www.opdivo.com

INDICATIONS

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) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

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 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.

Immune-Mediated Hepatitis and Hepatotoxicity

OPDIVO and YERVOY can cause immune-mediated hepatitis.

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.

Immune-Mediated Nephritis with Renal Dysfunction

OPDIVO and YERVOY can cause immune-mediated nephritis.

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).

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.

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 -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 -9LA, serious adverse reactions occurred in 57% of patients (n=358). The most frequent (>2%) serious adverse reactions were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis, and respiratory failure. Fatal adverse reactions occurred in 7 (2%) patients, and included hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia, and massive hemoptysis in the setting of thrombocytopenia.

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%).

In CheckMate -9LA, the most common (>20%) adverse reactions were fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%),
rash (30%), decreased appetite (28%), constipation (21%), and pruritus (21%).

Please see US Full Prescribing Information for OPDIVO and YERVOY.

Clinical Trials and Patient Populations

CheckMate -227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; CheckMate -9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology

References

  1. National Cancer Institute. Non-Small Cell Lung Cancer Treatment (PDQ®) – Health Professional Version. https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq#_4. Accessed May 10, 2021.
  2. SEER. Lung and Bronchus Cancer, CSR 1975-2016.  https://seer.cancer.gov/csr/1975_2017/results_merged/sect_15_lung_bronchus.pdf. Accessed May 10, 2021.
  3. Opdivo Prescribing Information. Opdivo U.S. Product Information. Last updated: April 2021. Princeton, NJ; Bristol-Myers Squibb Company.
  4. Paz-Ares L, Ciuleanu T, Lee J, et al. Nivolumab + ipilimumab vs chemotherapy as first-line treatment for advanced non-small cell lung cancer: 4-year update from CheckMate 227 [abstract]. In: ASCO Annual Meeting; June 4 – June 8, 2021; Virtual.
  5. Reck M, Ciuleanu T, Cobo M, et al. First-line nivolumab + ipilimumab + 2 cycles of chemotherapy versus chemotherapy alone (4 cycles) in patients with advanced non-small cell lung cancer: 2-year update from CheckMate 9LA [abstract]. In: ASCO Annual Meeting; June 4 – June 8, 2021; Virtual.
  6. Hellmann M, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus Ipilimumab in Advanced Non-Small Cell Lung Cancer. N Engl J Med 2019; 381:2020-31.
  7. Ramalingam S, Ciuleanu T, Pluzanski A, et al. Nivolumab (NIVO) + ipilimumab (IPI) versus platinum-doublet chemotherapy (chemo) as first-line (1L) treatment for advanced non-small cell lung cancer (aNSCLC): 3-year update from CheckMate 227 Part 1 [abstract]. In: ASCO Annual Meeting; 2020 May 29 – June 2; Virtual.

© 2021 Bristol-Myers Squibb Company.

OPDIVO® and YERVOY® are registered trademarks of Bristol-Myers Squibb Company.

7356-US-2100808 11/21



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