OPDIVO- nivolumab injection

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

NIVOLUMAB (UNII: 31YO63LBSN) (NIVOLUMAB - UNII:31YO63LBSN)

Available from:

E.R. Squibb & Sons, L.L.C.

INN (International Name):

NIVOLUMAB

Composition:

NIVOLUMAB 10 mg in 1 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

OPDIVO, as a single agent or in combination with ipilimumab, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO 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, 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, in combination with ipilimumab, is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma. OPDIVO is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after: This indication is approved under accelerated approval based on overall response rate [see Clinical Studies (14.7)] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy. OPDIVO 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 [see Clinical Studies (14.9)]. OPDIVO, in combination with cisplatin and gemcitabine, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma. OPDIVO is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who: OPDIVO, as a single agent or in combination with ipilimumab, is indicated for the treatment of adult and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14.10)] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO, in combination with ipilimumab, is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14.11)] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. OPDIVO, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. None. Based on data from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)] , OPDIVO can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of nivolumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased abortion and premature infant death (see Data) . Human IgG4 is known to cross the placental barrier and nivolumab is an immunoglobulin G4 (IgG4); therefore, nivolumab has the potential to be transmitted from the mother to the developing fetus. The effects of OPDIVO are likely to be greater during the second and third trimesters of pregnancy. There are no available data on OPDIVO use in pregnant women to evaluate a drug-associated risk. Advise pregnant women of the potential risk to a fetus. The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Animal Data A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. Blockade of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to the fetus and to increase fetal loss. The effects of nivolumab on prenatal and postnatal development were evaluated in monkeys that received nivolumab twice weekly from the onset of organogenesis through delivery, at exposure levels of between 9 and 42 times higher than those observed at the clinical dose of 3 mg/kg (based on AUC). Nivolumab administration resulted in a non-dose-related increase in spontaneous abortion and increased neonatal death. Based on its mechanism of action, fetal exposure to nivolumab may increase the risk of developing immune-mediated disorders or altering the normal immune response and immune-mediated disorders have been reported in PD-1 knockout mice. In surviving infants (18 of 32 compared to 11 of 16 vehicle-exposed infants) of cynomolgus monkeys treated with nivolumab, there were no apparent malformations and no effects on neurobehavioral, immunological, or clinical pathology parameters throughout the 6-month postnatal period. There are no data on the presence of nivolumab in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for 5 months after the last dose of OPDIVO. Verify the pregnancy status of females of reproductive potential prior to initiating OPDIVO [see Use in Specific Populations (8.1)] . OPDIVO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and for 5 months following the last dose. The safety and effectiveness of OPDIVO have been established in pediatric patients aged 12 years and older for the following indications: as a single agent and in combination with ipilimumab for the treatment of unresectable or metastatic melanoma, as a single agent for the adjuvant treatment of completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma and, as a single agent or in combination with ipilimumab for the treatment of MSI-H or dMMR mCRC that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Use of OPDIVO for these indications is supported by evidence from adequate and well-controlled studies in adults with melanoma or MSI-H or dMMR mCRC and additional pharmacokinetic data in pediatric patients. Nivolumab exposure in pediatric patients 12 years and older is comparable to that of adults and the courses of melanoma and MSI-H or dMMR mCRC are similar in pediatric patients aged 12 years and older to that of adults to allow extrapolation of safety and efficacy [see Adverse Reactions (6.1), Clinical Pharmacology (12.3) , Clinical Studies (14.1 , 14.10)] . The safety and effectiveness of OPDIVO have not been established for pediatric patients younger than 12 years old with melanoma or MSI-H or dMMR mCRC. The safety and effectiveness of OPDIVO have not been established in pediatric patients with non-small cell lung cancer, malignant pleural mesothelioma, advanced renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, hepatocellular carcinoma, esophageal cancer, gastric cancer, gastroesophageal cancer and esophageal adenocarcinoma. Single Agent Of 3569 patients with melanoma, NSCLC, renal cell carcinoma, urothelial carcinoma, ESCC, and esophageal or gastroesophageal junction cancer who were randomized to single agent OPDIVO in clinical studies, 41% were 65 years and over and 10% were 75 years and over. No overall differences in safety or effectiveness were observed between elderly patients and younger patients [see Clinical Studies (14.1, 14.2, 14.4, 14.6, 14.9, 14.12)]. In patients with cHL, recurrent head and neck SCC, or dMMR or MSI-H metastatic CRC (mCRC) who were treated with single agent OPDIVO in clinical studies did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients [see Clinical Studies (14.7, 14.8, 14.10)]. In Combination with Ipilimumab Of the 314 patients with melanoma who were randomized to OPDIVO in combination with ipilimumab, 41% were 65 years or older and 11% were 75 years or older. No overall differences in safety or effectiveness were reported between elderly patients and younger patients [see Clinical Studies (14.1)]. Of the 576 patients with NSCLC who were randomized to OPDIVO in combination with ipilimumab, 48% were 65 years or older and 10% were 75 years or older. No overall difference in safety was reported between older patients and younger patients; however, there was a higher discontinuation rate due to adverse reactions in patients aged 75 years or older (29%) relative to all patients who received OPDIVO with ipilimumab (18%). Of the 396 patients in the primary efficacy population (PD-L1 ≥1%) randomized to OPDIVO in combination with ipilimumab, the hazard ratio for overall survival was 0.70 (95% CI: 0.55, 0.89) in the 199 patients younger than 65 years compared to 0.91 (95% CI: 0.72, 1.15) in the 197 patients 65 years or older [see Clinical Studies (14.3)]. Of the 303 patients with malignant pleural mesothelioma who were randomized to OPDIVO in combination with ipilimumab, 77% were 65 years old or older and 26% were 75 years or older. No overall difference in safety was reported between older patients and younger patients; however, there were higher rates of serious adverse reactions and discontinuation due to adverse reactions in patients aged 75 years or older (68% and 35%, respectively) relative to all patients who received OPDIVO with ipilimumab (54% and 28%, respectively). For patients aged 75 years or older who received chemotherapy, the rate of serious adverse reactions was 34% and the discontinuation rate due to adverse reactions was 26% relative to 28% and 19% respectively for all patients. The hazard ratio for overall survival was 0.76 (95% CI: 0.52, 1.11) in the 71 patients younger than 65 years compared to 0.74 (95% CI: 0.59, 0.93) in the 232 patients 65 years or older randomized to OPDIVO in combination with ipilimumab [see Clinical Studies (14.5)]. Of the 550 patients with renal cell carcinoma who were randomized to OPDIVO in combination with ipilimumab, 38% were 65 years or older and 8% were 75 years or older. No overall difference in safety was reported between elderly patients and younger patients. In elderly patients with intermediate or poor risk, no overall difference in effectiveness was reported [see Clinical Studies (14.6)]. Of the 49 patients with hepatocellular carcinoma who were treated with OPDIVO in combination with ipilimumab, 29% were between 65 years and 74 years of age and 8% were 75 years or older. Clinical studies of OPDIVO in combination with ipilimumab did not include sufficient numbers of patients with hepatocellular carcinoma aged 65 and over to determine whether they respond differently from younger patients [see Clinical Studies (14.11)]. Of the 325 patients with ESCC who were randomized to OPDIVO in combination with ipilimumab, 43% were 65 years old or older and 7% were 75 years or older. No overall difference in safety was reported between older patients and younger patients; however, there was a higher discontinuation rate due to adverse reactions in patients aged 75 years or older (38%) relative to all patients who received OPDIVO with ipilimumab (23%). For patients aged 75 years or older who received chemotherapy, the discontinuation rate due to adverse reactions was 33% relative to 23% for all patients [see Clinical Studies (14.12)]. In Combination with Platinum-Containing Chemotherapy Of the 179 patients with NSCLC who were randomized to OPDIVO in combination with platinum-doublet chemotherapy, 48% were 65 years old or older and 6% were 75 years old or older. No overall differences in safety or effectiveness were reported between patients older and younger than 65 years [see Clinical Studies (14.3)]. Of the 1,110 patients with ESCC, GC, GEJC, or EAC who were randomized to OPDIVO in combination with fluoropyrimidine- and platinum-containing chemotherapy), 42% were 65 years or older and 10% were 75 years or older. No overall difference in safety was reported between elderly patients and younger patients [see Clinical Studies (14.12, 14.13)] . Of the 304 patients with UC who were treated with OPDIVO in combination with gemcitabine and platinum-doublet chemotherapy, 40% were 65 years or older and 11% were 75 years or older. No overall differences in safety or effectiveness were observed between patients 65 years of age and over and younger patients. Clinical studies of OPDIVO with platinum-doublet chemotherapy did not include sufficient numbers of patients aged 75 years and over to determine whether safety and effectiveness differs compared to younger patients. [see Clinical Studies (14.9)]. In Combination with Ipilimumab and Platinum-Doublet Chemotherapy Of the 361 patients with NSCLC who were randomized to OPDIVO in combination with ipilimumab and platinum-doublet chemotherapy, 51% were 65 years or older and 10% were 75 years or older. No overall difference in safety was reported between older patients and younger patients; however, there was a higher discontinuation rate due to adverse reactions in patients aged 75 years or older (43%) relative to all patients who received OPDIVO with ipilimumab and chemotherapy (24%). For patients aged 75 years or older who received chemotherapy only, the discontinuation rate due to adverse reactions was 16% relative to all patients who had a discontinuation rate of 13%. Based on an updated analysis for overall survival, of the 361 patients randomized to OPDIVO in combination with ipilimumab and platinum-doublet chemotherapy, the hazard ratio for overall survival was 0.61 (95% CI: 0.47, 0.80) in the 176 patients younger than 65 years compared to 0.73 (95% CI: 0.56, 0.95) in the 185 patients 65 years or older [see Clinical Studies (14.4)]. In Combination with Cabozantinib Of the 320 patients with renal cell carcinoma who were treated with OPDIVO in combination with cabozantinib, 41% were 65 years or older and 9% were 75 years or older. No overall difference in safety was reported between elderly patients and younger patients [see Clinical Studies (14.6)].

Product summary:

OPDIVO® (nivolumab) Injection is a clear to opalescent, colorless to pale-yellow solution in a single-dose vial available as follows: Carton Contents NDC 40 mg/4 mL (10 mg/mL) single-dose vial 0003-3772-11 100 mg/10 mL (10 mg/mL) single-dose vial 0003-3774-12 120 mg/12 mL (10 mg/mL) single-dose vial 0003-3756-14 240 mg/24 mL (10 mg/mL) single-dose vial 0003-3734-13 Store under refrigeration at 2°C to 8°C (36°F to 46°F). Protect from light by storing in the original package until time of use. Do not freeze or shake.

Authorization status:

Biologic Licensing Application

Patient Information leaflet

E.R. Squibb & Sons, L.L.C.
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MEDICATION GUIDE
OPDIVO® (op-DEE-voh)
(nivolumab)
injection
Read this Medication Guide before you start receiving OPDIVO and
before each infusion. There may be
new information. If your healthcare provider prescribes OPDIVO in
combination with ipilimumab, also
read the Medication Guide that comes with ipilimumab. If your
healthcare provider prescribes OPDIVO
in combination with cabozantinib, also read the Patient Information
that comes with cabozantinib. This
Medication Guide does not take the place of talking with your
healthcare provider about your medical
condition or your treatment.
What is the most important information I should know about OPDIVO?
OPDIVO is a medicine that may treat certain cancers by working with
your immune system. OPDIVO
can cause your immune system to attack normal organs and tissues in
any area of your body and can
affect the way they work. These problems can sometimes become severe
or can lead to death. These
problems may happen anytime during treatment or even after your
treatment has ended. You may have
more than one of these problems at the same time. Some of these
problems may happen more often when
OPDIVO is used in combination with another therapy.
Call or see your healthcare provider right away if you develop any new
or worse signs or symptoms,
including:
Lung problems.
•
new or worsening cough
•
shortness of breath
•
chest pain
Intestinal problems.
•
diarrhea (loose stools) or more frequent bowel movements than usual
•
stools that are black, tarry, sticky, or have blood or mucus
•
severe stomach-area (abdominal) pain or tenderness
Liver problems.
•
yellowing of your skin or the whites of your
eyes
•
severe nausea or vomiting
•
pain on the right side of your stomach area
(abdomen)
•
dark urine (tea colored)
•
bleeding or bruising more easily than normal
Hormone gland problems.
•
headaches that will not go away or unusual
headaches
•
eye sensitivity to light
•
eye problems
•
rapid heartbeat
•
increased sweating

Summary of Product characteristics

OPDIVO- NIVOLUMAB INJECTION
E.R. SQUIBB & SONS, L.L.C.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
OPDIVO SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR OPDIVO.
OPDIVO® (NIVOLUMAB) INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2014
RECENT MAJOR CHANGES
Indications and Usage (1)
3/2024
Dosage and Administration (2)
3/2024
Warnings and Precautions (5.1)
3/2024
INDICATIONS AND USAGE
OPDIVO is a programmed death receptor-1 (PD-1)-blocking antibody
indicated for the treatment of:
Melanoma
•
•
Non-Small Cell Lung Cancer (NSCLC)
•
•
•
•
Malignant Pleural Mesothelioma
•
Renal Cell Carcinoma (RCC)
•
•
•
Classical Hodgkin Lymphoma (cHL)
•
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
•
adult and pediatric (12 years and older) patients with unresectable or
metastatic melanoma, as a
single agent or in combination with ipilimumab. (1.1)
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. (1.2)
adult patients with resectable (tumors ≥4 cm or node positive)
non-small cell lung cancer in the
neoadjuvant setting, in combination with platinum-doublet
chemotherapy. (1.3)
adult patients with metastatic non-small cell lung cancer expressing
PD-L1 (≥1%) as determined by
an FDA-approved test, with no EGFR or ALK genomic tumor aberrations,
as first-line treatment in
combination with ipilimumab. (1.4)
adult patients with metastatic or recurrent non-small cell lung cancer
with no EGFR or ALK genomic
tumor aberrations as first-line treatment, in combination with
ipilimumab and 2 cycles of platinum-
doublet chemotherapy. (1.4)
adult patients with metastatic non-small cell lung cancer and
progression on or after platinum-based
chemotherapy. Patients with EGFR or ALK genomic tumor aberrations
should have disease
progression on FDA-approved therapy for these aberrations prior to
receiving OPDIVO. (1.4)
adult pati