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Full Indication

For Patients With Previously Treated Metastatic Non-Small Cell Lung Cancer

 
 

SECOND LINE IS A
SECOND CHANCE

 
FOR
SURVIVAL1,2*

5 years of OS data in 2L mNSCLC1,2

In the primary analysis for CM 057 and CM 017, the median OS was 12.2 months (95% CI: 9.7–15.0) with OPDIVO vs 9.4 months (95% CI: 8.0–10.7) with docetaxel (HR=0.73 [95% CI: 0.60–0.89]; P=0.0015), and 9.2 months (95% CI: 7.3–13.3) with OPDIVO vs 6.0 months (95% CI: 5.1–7.3) with docetaxel (HR=0.59 [95% CI: 0.44–0.79]; P=0.0002), respectively.

In the primary analysis for CM 057 and CM 017, the median OS was 12.2 months (95% CI: 9.7–15.0) with OPDIVO vs 9.4 months (95% CI: 8.0–10.7) with docetaxel (HR=0.73 [95% CI: 0.60–0.89]; P=0.0015), and 9.2 months (95% CI: 7.3–13.3) with OPDIVO vs 6.0 months (95% CI: 5.1–7.3) with docetaxel (HR=0.59 [95% CI: 0.44–0.79]; P=0.0002), respectively.

In a pooled analysis of CM 057 and CM 017, the median OS was 11.1 months (95% CI: 9.2–13.1) with OPDIVO vs 8.1 months (95% CI: 7.2–9.2) with docetaxel (HR=0.68, 95% CI: 0.59–0.78);
the landmark 5-year OS rate with OPDIVO was 13.4% vs 2.6% with docetaxel.1,2

*vs docetaxel.2

In a pooled analysis of CM 057 and CM 017, the
median OS was 11.1 months (95% CI: 9.2–13.1)
with OPDIVO vs 8.1 months (95% CI: 7.2–9.2) with
docetaxel (HR=0.68, 95% CI: 0.59–0.78);
the landmark 5-year OS rate with
OPDIVO was 13.4% vs 2.6% with docetaxel.1,2

*vs docetaxel.2


Scroll to see primary and follow-up data below


In the Initial Analysis:

 

In previously treated non-squamous and squamous mNSCLC
OPDIVO: The only I-O therapy to achieve superior OS vs chemotherapy* in two
phase 3 studies designed to include PD-L1 expressors and non-expressors1,2

An overview of Checkmate 057 and Checkmate 017, a phase 3 study for patients taking OPDIVO® (nivolumab) versus patients taking docetaxel.An overview of Checkmate 057 and Checkmate 017, a phase 3 study for patients taking OPDIVO® (nivolumab) versus patients taking docetaxel.

Both trials stopped early due
to superior OS3,4

More patients treated in
2L mNSCLC than
any other I-O therapy1,5

Non-Squamous (NSQ)1

  • OPDIVO ORR was 19% (4 CRs, 95% CI: 15–24) vs 12%
    with docetaxel (1 CR, 95% CI: 9–17); P=0.02
  • mPFS was 2.3 months with OPDIVO vs 4.2 months with
    docetaxel; HR=0.92 (95% CI: 0.77–1.11); P=0.39

Squamous (SQ)1

  • OPDIVO ORR was 20% (1 CR, 95% CI: 14–28) vs 9%
    with docetaxel (0 CRs, 95% CI: 5–15); P=0.0083
  • mPFS was 3.5 months with OPDIVO vs 2.8 months with
    docetaxel; HR=0.62 (95% CI: 0.47–0.81); P=0.0004

Select Important Safety Information

Serious Adverse Reactions

  • In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418).
    The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 057, fatal adverse reactions occurred; these included events of infection (7 patients, including one case of Pneumocystis jirovecii pneumonia), pulmonary embolism (4 patients), and limbic encephalitis (1 patient). 

Common Adverse Reactions

  • In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

 

*vs docetaxel.1

Results were based on the pre-specified interim analysis. Minimum follow-up of 11 months for Checkmate 017 and 13.2 months for Checkmate 057.1,6,7

In the Extended Follow-Up at
5 Years:

 

In a pooled analysis of two
phase 3 trials

OPDIVO showed long-term 5-year OS in non-squamous and squamous mNSCLC2*

In a pooled analysis of two phase 3 trials
OPDIVO showed long-term 5-year OS in non-squamous and squamous mNSCLC2*

Pooled 5-year extended overall survival analysis2‡§

Graph of overall survival in the intent-to-treat population at 5 years for patients taking OPDIVO® (nivolumab) versus patients taking docetaxel. Graph of overall survival in the intent-to-treat population at 5 years for patients taking OPDIVO® (nivolumab) versus patients taking docetaxel.

*vs docetaxel.2

A pooled analysis of CM 017 and CM 057. CM 017 and CM 057 were registrational, randomized, phase 3 studies of OPDIVO vs
docetaxel in patients with 2L SQ or 2L/3L NSQ mNSCLC, respectively.2

§The pooled patient population (n=427) for OPDIVO consisted of 292 patients with NSQ and 135 with SQ histology. The pooled
patient population (n=427) for docetaxel consisted of 290 patients with NSQ and 137 with SQ histology.1,2


Longest follow-up of two phase 3 trials in 2L mNSCLC regardless of PD-L1 expression2

 
 

In the Extended Follow-Up at
5 Years:

 

In a pooled analysis of two phase 3 trials that evaluated non-squamous and squamous mNSCLC
Among OPDIVO responders,|| mOS was not reached at 5 years2,8,9||

CM 057 and CM 017
pooled ORR2#**

 Overall response rate at 4 years from Checkmate 057 and Checkmate 017, a phase 3 study for patients taking OPDIVO® (nivolumab) versus patients taking docetaxel.  Overall response rate at 4 years from Checkmate 057 and Checkmate 017, a phase 3 study for patients taking OPDIVO® (nivolumab) versus patients taking docetaxel.

Pooled 5-year extended
overall survival analysis in complete and partial responders2,8,9||#

Graph of median overall survival post response and median duration of response post response in the intent-to-treat population at 4 years for patients taking OPDIVO® (nivolumab) versus patients taking docetaxel. Graph of median overall survival post response and median duration of response post response in the intent-to-treat population at 4 years for patients taking OPDIVO® (nivolumab) versus patients taking docetaxel.

53% of OPDIVO responders||
were alive at 5 years8,9

||OS was calculated from the time of response (CR/PR) for each responder.8

A pooled analysis of CM 017 and CM 057. CM 017 and CM 057 were registrational, randomized, phase 3 studies of OPDIVO vs docetaxel in patients with 2L SQ or 2L/3L NSQ mNSCLC, respectively. The pooled patient population (n=427) for OPDIVO consisted of 292 patients with NSQ and 135 with SQ histology. The pooled patient population (n=427) for docetaxel consisted of 290 patients with NSQ and 137 with SQ histology.8

#Since the initial analysis of the CM 057 study, 1 patient's response changed from SD to PR, and 1 from PR to CR.2

**In CM 057, the ORR was 19% (56/292; 4 CRs) (95% CI: 15–24) with OPDIVO vs 12% (36/290;
1 CR) (95% CI: 9–17) with docetaxel; P=0.02. The median duration of response was 17 months in the OPDIVO arm (95% CI: 8.4–NR) and 6 months in the docetaxel arm (95% CI: 4.4–7.0).1 In CM 017, the ORR was 20% (27/135; 1 CR) (95% CI: 14–28) with OPDIVO vs 9% (12/137; 0 CRs) (95% CI: 5–15) with docetaxel; P=0.0083.1 The median duration of response was NR months in the OPDIVO arm (95% CI: 9.8–NR) and 8.4 months in the docetaxel arm (95% CI: 3.6–10.8).1

Select Safety Profile:

 

For previously treated mNSCLC
OPDIVO selected safety profile1,2

Adverse reactions occurring in ≥10% (all grades) of patients treated with OPDIVO
and at a higher incidence than docetaxel (between-arm difference of ≥5% [all grades]
or ≥2% [Grades 3-4]) in Checkmate 017 and 0571

 OPDIVO
(n=418)
Docetaxel
(n=397)
Adverse reactionsAll gradesGrades 3-4All gradesGrades 3-4

Respiratory, thoracic, and mediastinal disorders, %

Cough

310.7240

Metabolism and
nutrition disorders, %

Decreased appetite

281.4231.5

Skin and subcutaneous tissue disorders, %

Pruritus

100.22.00
 OPDIVO
(n=418)
Docetaxel
(n=397)
Adverse reactionsAll gradesAll grades

Respiratory, thoracic,
and mediastinal disorders, %

Cough

3124

Metabolism and nutrition disorders, %

Decreased
appetite

2823

Skin and subcutaneous tissue disorders, %

Pruritus

102.0
 OPDIVO
(n=418)
Docetaxel
(n=397)
Adverse reactionsGrades 3-4Grades 3-4

Respiratory, thoracic,
and mediastinal disorders, %

Cough

0.70

Metabolism and nutrition disorders, %

Decreased
appetite

1.41.5

Skin and subcutaneous tissue disorders, %

Pruritus

0.20
  • The safety profile of OPDIVO was evaluated across squamous and non-squamous histologies in
    patients with previously treated mNSCLC
  • The most common adverse reactions (reported in ≥20% of patients) were fatigue, musculoskeletal
    pain, cough, dyspnea, and decreased appetite
  • Serious adverse reactions occurred in 46% of patients receiving OPDIVO
    • The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were
      pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure
  • OPDIVO was discontinued due to adverse reactions in 11% of patients
  • 28% of patients receiving OPDIVO had a drug delay for an adverse reaction
  • With 5 years minimum follow-up, no new safety signals were identified for OPDIVO2

2L=second-line; 3L=third-line; CI=confidence interval; CM=Checkmate; CR=complete response; DOR=duration of response;
HR=hazard ratio;
I-O=immuno-oncology; mNSCLC=metastatic non-small cell lung cancer; mOS=median OS;
mos=months; mPFS=median progression-free survival; NR=not reached; ORR=overall response rate; OS=overall survival;
PD-L1=programmed death-ligand 1; PR=partial response.


Select Important Safety
Information

OPDIVO is associated with the following Warnings and Precautions: severe and fatal immune‑mediated adverse reactions including pneumonitis, colitis, hepatitis, 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 thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.

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. Early identification and management are essential to ensure safe use of OPDIVO. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment with OPDIVO. 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 depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO 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 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%).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. 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%).

Immune-Mediated Hepatitis

OPDIVO 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%). 

Immune-Mediated Endocrinopathies

OPDIVO 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 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 monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%).

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%).

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 monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%).

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.

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO 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%).

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.

Withhold or permanently discontinue OPDIVO 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%).

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 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.

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, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

OPDIVO can cause severe infusion-related reactions. Discontinue OPDIVO 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.

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. 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 and allogeneic HSCT.

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

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal studies, OPDIVO 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 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 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 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure.In Checkmate 057, fatal adverse reactions occurred; these included events of infection (7 patients, including one case of Pneumocystis jirovecii pneumonia), pulmonary embolism (4 patients), and limbic encephalitis (1 patient).

Common Adverse Reactions

In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

OPDIVO (10 mg/mL) is an injection for intravenous (IV) use.

Please see U.S. Full Prescribing Information for OPDIVO.

References:

  1. OPDIVO [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2020.
  2. Gettinger S, Borghaei H, Brahmer J, et al. Five-year outcomes from the randomized, phase 3 trials CheckMate 017/057: Nivolumab vs docetaxel in previously treated NSCLC. Presentation WCLC19. Presented at: IASLC 2019 World Conference on Lung Cancer: September 7-10, 2019: Barcelona, Spain. Abstract OA14.04.
  3. Bristol Myers Squibb. CheckMate-057, a pivotal phase III Opdivo (nivolumab) lung cancer trial, stopped early [press release]. April 17, 2015. https://news.bms.com/press-release/checkmate-057-pivotal-phase-iii-opdivo-nivolumab-lung-cancer-trial-stopped-early. Accessed
    June 19, 2019.
  4. Bristol Myers Squibb. CheckMate-017, a phase 3 study of Opdivo (nivolumab) compared to docetaxel in patients with second-line squamous cell non-small cell lung cancer, stopped early [press release]. January 11, 2015.
    https://news.bms.com/press-release/checkmate-017-phase-3-study-opdivo-nivolumab-compared-docetaxel-patients-second-line-s. Accessed
    June 19, 2019.
  5. IMS APLD data. April 2018-September 2018.
  6. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N Engl J Med. 2015;373(17):1627-1639.
  7. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer. N Engl J Med. 2015;373(2):123-135.
  8. Brahmer J, Borghaei H, Ramalingam SS, et al. Long-term survival outcomes with nivolumab in patients with previously treated advanced non-small cell lung cancer: impact of early disease control and response. Post presentation at AACR 2019. Abstract CT195.
  9. Data on file. NIVO 532. Princeton, NJ: Bristol-Myers Squibb Company; 2019.