Approval is based on the CheckMate-77T trial, in which the
Opdivo-
based
regimen demonstrated significantly longer event-free survival compared to the chemotherapy and placebo arm; a high pathologic complete response rate was also observed
1
Opdivo
is the only approved PD-1 inhibitor for resectable NSCLC in both a neoadjuvant-only regimen and as part of a perioperative treatment regimen
1
This milestone adds to Bristol Myers Squibb’s thoracic portfolio and highlights the company’s commitment to advancing treatments for patients with early-stage disease
PRINCETON, N.J.--(BUSINESS WIRE)--
$BMY
#CheckMate
--
Bristol Myers Squibb
(NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) approved
Opdivo
®
(nivolumab) for the treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, for neoadjuvant treatment, in combination with platinum-doublet chemotherapy,
followed by single-agent
Opdivo
as adjuvant treatment after surgery – otherwise referred to as perioperative therapy, which is used before and after surgery.
1
The approval is based on results from the CheckMate-77T trial, the company’s second positive Phase 3 randomized trial with an immunotherapy-based combination for the treatment of resectable NSCLC.
1
Opdivo
is now the only PD-1 inhibitor to demonstrate statistically significant and clinically meaningful benefits in this disease versus chemotherapy in both a neoadjuvant-only regimen and as part of a perioperative regimen.
1
“Given the rates of disease recurrence in patients with resectable NSCLC, there is a clear need for options that can be administered before and after surgery that may target micrometastasis, help reduce the risk of cancer returning and improve the chance of successful surgical treatment,” said Tina Cascone, MD, PhD, associate professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center.
2,3,4
“This approval is a step forward for patients with resectable disease, as the perioperative nivolumab plus neoadjuvant chemotherapy regimen can offer an improved event free survival (EFS) compared with neoadjuvant chemotherapy alone and has the potential for achieving a pathologic response (pCR) in one in four patients.”
2
The CheckMate-77T trial evaluated the perioperative regimen of neoadjuvant
Opdivo
with platinum-doublet chemotherapy followed by surgery and adjuvant
Opdivo
monotherapy (n=229), compared to neoadjuvant platinum-doublet chemotherapy and placebo followed by surgery and adjuvant placebo (n=232) in adult patients with resectable NSCLC.
2
In the trial, the
Opdivo
arm improved EFS, a primary endpoint, compared to the chemotherapy and placebo treatment arm.
2
A high pCR rate was also observed as one of the pre-specified secondary endpoints.
2
The risk of disease recurrence, progression or death was reduced by 42% (EFS Hazard Ratio [HR] 0.58; 95% Confidence Interval [CI]: 0.43 to 0.78;
P
=0.00025) in patients treated in the
Opdivo
arm, compared to the chemotherapy and placebo arm, with a median follow-up of 25.4 months.
2
In addition, 18-month EFS was demonstrated in 70% of patients in the
Opdivo
arm, compared to 50% of patients in the chemotherapy and placebo arm.
2
Furthermore, 25% of patients in the
Opdivo
arm achieved pCR, while 4.7% of patients in the comparator arm achieved pCR in the intent-to-treat population (estimated treatment difference of 20.5%; 95% CI,14.3 to 26.6).
2
Opdivo
is associated with the following Warnings & Precautions: severe and fatal immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis and renal dysfunction; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity.
1
Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue and dexamethasone is not recommended outside of controlled clinical trials.
1
Please see Important Safety Information below.
“This milestone expands the role of
Opdivo
-based treatments and builds upon the foundation set by the FDA approval of neoadjuvant-only
Opdivo
plus chemotherapy in resectable NSCLC based on the CheckMate-816 trial,” said Wendy Short Bartie, senior vice president of U.S. Oncology and Hematology at Bristol Myers Squibb.
1
“With this new
Opdivo
-based regimen, we are reinforcing our commitment to helping improve patient outcomes and expanding our thoracic portfolio in early-stage disease.”
The recommended dose for
Opdivo
in this indication is 360 mg with platinum-doublet chemotherapy on the same day every three weeks for up to four cycles or until disease progression or unacceptable toxicity, then continued as a single-agent
Opdivo
480 mg every four weeks after surgery for up to 13 cycles (approximately one year) or until disease recurrence or unacceptable toxicity.
1
The FDA previously approved
Opdivo
for adult patients with resectable (tumors ≥4 cm or node positive) NSCLC in the neoadjuvant setting, in combination with platinum-doublet chemotherapy.
1
Opdivo
and
Opdivo
-based combinations have been approved by the FDA in the neoadjuvant, adjuvant or perioperative settings across four cancers to date, including lung cancer, melanoma, bladder cancer and esophageal/gastroesophageal junction cancer.
1
About CheckMate-77T
CheckMate-77T is a Phase 3 randomized, double-blind, multi-center trial evaluating neoadjuvant
Opdivo
in combination with platinum-doublet chemotherapy followed by surgery and single-agent adjuvant
Opdivo,
compared to neoadjuvant platinum-doublet chemotherapy and placebo followed by surgery and adjuvant placebo in patients with resectable NSCLC.
5
In the CheckMate-77T study, a total of 461 patients were randomized to receive either neoadjuvant
Opdivo
360 mg with platinum-doublet chemotherapy every three weeks, or placebo and platinum-doublet chemotherapy every three weeks, until disease progression or unacceptable toxicity, for up to four cycles, followed by single-agent
Opdivo
480 mg after surgery every four weeks or placebo every four weeks, until disease progression or unacceptable toxicity, for up to thirteen cycles (approximately one year).
1
The primary endpoint of the trial is event-free survival determined by Blinded Independent Central Review (BICR). Secondary endpoints of the trial include pathologic complete response and major pathologic response, both determined by Blinded Independent Pathological Review (BIPR), as well as overall survival and safety.
2
Select Safety Pro
CheckMate-77T
The most common adverse reactions (reported in ≥20%) in patients receiving
Opdivo
in combination with chemotherapy (n= 228) were anemia (39.5%), constipation (32.0%), nausea (28.9%), fatigue (28.1%), alopecia (25.9%), and cough (21.9%).
6
Serious adverse reactions occurred in 21% of patients who received
Opdivo
in combination with platinum-doublet chemotherapy as neoadjuvant treatment (n=228).
1
The most frequent (≥2%) serious adverse reaction was pneumonia.
1
Fatal adverse reactions occurred in 2.2% of patients, due to cerebrovascular accident, COVID-19 infection, hemoptysis, pneumonia, and pneumonitis (0.4% each).
1
In Checkmate 77T, 5.3% (n=12) of the OPDIVO-treated patients who received neoadjuvant treatment, did not receive surgery due to adverse reactions. The adverse reactions that led to cancellation of surgery in OPDIVO-treated patients were cerebrovascular accident, pneumonia, and colitis/diarrhea (2 patients each) and acute coronary syndrome, myocarditis, hemoptysis, pneumonitis, COVID-19, and myositis (1 patient each).
Serious adverse reactions occurred in 22% of the patients who received single-agent
Opdivo
as adjuvant treatment (n=142).
1
The most frequent serious adverse reaction was pneumonitis/ILD (2.8%).
1
One fatal adverse event due to COVID-19 occurred.
1
The perioperative regimen had a safety pro with previously reported
Opdivo
studies in NSCLC and no new safety signals were identified.
2
About Lung Cancer
Lung cancer is the leading cause of cancer deaths in the United States.
7
The two main types of lung cancer are non-small cell and small cell.
7
Non-small cell lung cancer (NSCLC) represents up to 85% of diagnoses.
7
For some non-metastatic early-stage NSCLC patients, surgery may be able to be used as a singular option for treatment.
8
However, 30% to 55% of patients can develop recurrence, contributing to a need for treatment options administered before surgery (neoadjuvant) and after surgery (adjuvant) to improve long-term outcomes.
2
Survival rates vary depending on the stage and type of the cancer when diagnosed.
7
INDICATIONS
OPDIVO
®
(nivolumab) is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.
OPDIVO
®
(nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).
OPDIVO
®
(nivolumab) in combination with platinum-doublet chemotherapy, is indicated for neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by single-agent OPDIVO
®
as adjuvant treatment after surgery.
OPDIVO
®
(nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.
OPDIVO
®
(nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).
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 (2% included pneumonia and vomiting. No fatal adverse reactions occurred in patients who received OPDIVO in combination with platinum-doublet chemotherapy. In Checkmate 77T, serious adverse reactions occurred in 21% of patients who received OPDIVO in combination with platinum-doublet chemotherapy as neoadjuvant treatment (n=228). The most frequent (≥2%) serious adverse reactions was pneumonia. Fatal adverse reactions occurred in 2.2% of patients, due to cerebrovascular accident, COVID-19 infection, hemoptysis, pneumonia, and pneumonitis (0.4% each). In the adjuvant phase of Checkmate 77T, 22% of patients experienced serious adverse reactions (n=142). The most frequent serious adverse reaction was pneumonitis/ILD (2.8%). One fatal adverse reaction due to COVID-19 occurred. In Checkmate 274, serious adverse reactions occurred in 30% of patients receiving OPDIVO (n=351). The most frequent serious adverse reaction reported in ≥2% of patients receiving OPDIVO was urinary tract infection. Fatal adverse reactions occurred in 1% of patients; these included events of pneumonitis (0.6%). In Checkmate 577, serious adverse reactions occurred in 33% of patients receiving OPDIVO (n=532). A serious adverse reaction reported in ≥2% of patients who received OPDIVO was pneumonitis. A fatal reaction of myocardial infarction occurred in one patient who received OPDIVO. In Checkmate 76K, serious adverse reactions occurred in 18% of patients receiving OPDIVO (n=524). Adverse reactions which resulted in permanent discontinuation of OPDIVO in >1% of patients included arthralgia (1.7%), rash (1.7%), and diarrhea (1.1%). A fatal adverse reaction occurred in 1 (0.2%) patient (heart failure and acute kidney injury). The most frequent Grade 3-4 lab abnormalities reported in ≥1% of OPDIVO-treated patients were increased lipase (2.9%), increased AST (2.2%), increased ALT (2.1%), lymphopenia (1.1%), and decreased potassium (1.0%).
Common Adverse Reactions
In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%).
Contacts
Bristol Myers Squibb
Media Inquiries:
media@bms.com
Investors:
investor.relations@bms.com
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