Opdivo

Opdivo (nivolumab) is an immunotherapy treatment used to treat cancers such as melanoma, lung, colorectal, malignant pleural mesothelioma, urinary tract, gastric, liver, Hodgkin lymphoma, and head and neck cancers. It is administered as an intravenous infusion every 2 to 4 weeks, depending on your cancer type.

Opdivo (nivolumab) first gained FDA approval in 2014. There is no generic or biosimilar.

• Opdivo Qvantig is a subcutaneous formulation of Opdivo that has a faster rate of administration than Opdivo (3 to 5 minutes vs 30 minutes) but fewer approvals.

Melanoma

• Unresectable/metastatic melanoma in adults and children 12 years and older, as a single agent or in combination with ipilimumab.
• Completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma in adults and children 12 years and older.

Non-Small Cell Lung Cancer (NSCLC)

• Resectable (tumors ≥4 cm or node positive) NSCLC in adults, in the neoadjuvant setting (before surgery), in combination with platinum-doublet chemotherapy
• Resectable (tumors ≥4 cm or node positive) NSCLC in adults with no known EGFR mutations or ALK rearrangements, for neoadjuvant treatment, in combination with platinum-doublet chemotherapy, followed by single-agent Opdivo as adjuvant treatment after surgery
• Metastatic NSCLC in adults 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
• Metastatic or recurrent NSCLC in adults with no EGFR or ALK genomic aberrations as first-line treatment, in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy.
• Metastatic NSCLC in adults 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 before receiving Opdivo.

Malignant Pleural Mesothelioma

• Unresectable malignant pleural mesothelioma in adults, as first-line treatment in combination with ipilimumab

Renal Cell Carcinoma (RCC)

• Intermediate or poor risk advanced renal cell carcinoma (RCC) in adults as a first-line treatment in combination with ipilimumab
• Advanced RCC in adults as a first-line treatment in combination with cabozantinib
• Advanced RCC in adults who have received prior anti-angiogenic therapy.

Classical Hodgkin Lymphoma

• Previously untreated Stage III or IV classical Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine (AVD) in adults and pediatrics 12 years and older.
• Classical Hodgkin lymphoma in adults that has relapsed or progressed after: Autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin

or

• 3 or more lines of systemic therapy that includes autologous HSCT.

Squamous Cell Carcinoma of the Head and Neck (SCCHN)

• Recurrent or metastatic SCCHN in adults with disease progression on or after a platinum-based therapy.

Urothelial Carcinoma (UC)

• UC in adults at high risk of recurrence after undergoing radical resection of UC, as adjuvant treatment
• Unresectable or metastatic UC in adults as first-line treatment in combination with cisplatin and gemcitabine.
• Locally advanced or metastatic UC in adults who: Have disease progression during or following platinum-containing chemotherapy. Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Colorectal Cancer (CRC)

• Unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer (CRC) in adults and children 12+ in combination with ipilimumab.
• MSI-H or dMMR metastatic CRC in adults and children 12+ that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

Hepatocellular Carcinoma (HCC)

• Unresectable or metastatic HCC in adults, as a first-line treatment in combination with ipilimumab.
• Unresectable or metastatic HCC in adults who have been previously treated with sorafenib, in combination with ipilimumab.

Esophageal Cancer

• Completely resected esophageal or gastroesophageal junction cancer in adults with residual pathologic disease, who have received neoadjuvant chemoradiotherapy (CRT).
• Unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) in adults as first-line treatment in combination with fluoropyrimidine- and platinum-containing chemotherapy whose tumors express PD-L1 (≥1).
• Unresectable advanced or metastatic ESCC as first-line treatment in combination with ipilimumab, whose tumors express PD-L1 (≥1).
• Unresectable advanced, recurrent, or metastatic ESCC in adults after prior fluoropyrimidine- and platinum-based chemotherapy.

Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma

• Advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma in adults whose tumors express PD-L1 (≥1) in combination with fluoropyrimidine- and platinum-containing chemotherapy.

To make sure Opdivo is safe for you, tell your doctor if you:

• have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
• have received an organ or tissue transplant, including a corneal transplant
• have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
• have received radiation treatment to your chest area in the past, and have received other medicines that are similar to Opdivo
• have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed

Pregnancy

Opdivo may harm an unborn baby. Females who can become pregnant:

• Your healthcare provider should do a pregnancy test before you start receiving Opdivo
• You should use an effective method of birth control during treatment and for 5 months after your last dose of Opdivo. Talk to your healthcare provider about birth control methods you can use during this time
• Tell your healthcare provider right away if you become pregnant during treatment with Opdivo.

Breastfeeding

It is not known if Opdivo passes into your breast milk. Do not breastfeed while using this medicine, and for at least 5 months after your last dose.

Common Side Effects

Several side effects of Opdivo are common when Opdivo is used alone or with other treatments and include fatigue, nausea, rash, decreased appetite, constipation, muscle/bone/joint pain, and vomiting.

In addition to these, each combination may also cause:

• Opdivo alone: Diarrhea, fever, headache, weakness, abdominal pain, cough, shortness of breath, itching, upper respiratory tract infection, urinary tract infection
• + ipilimumab: Diarrhea, abdominal pain, shortness of breath, itching, upper respiratory tract infection, headache, hypothyroidism, fever, decreased weight, dizziness
• + platinum-based & another chemotherapy: Numbness/tingling/burning in hands and feet
• + ipilimumab, platinum-based, & another chemotherapy: Diarrhea, itching
• + cabozantinib: Diarrhea, weakness, liver problems, high blood pressure, hypothyroidism, hand/foot redness, pain, swelling or blisters, taste changes, abdominal pain, cough, upper respiratory tract infection, mouth sores
• + fluoropyrimidine & platinum-based chemotherapy: Mouth sores, diarrhea, abdominal pain, numbness/tingling/burning in hands and feet
• + doxorubicin, vinblastine & dacarbazine (AVD): Increased liver enzymes, low white blood cell count, numbness/tingling/burning in hands and feet, anemia, mouth sores

These are not all possible side effects of Opdivo. Contact your doctor for medical advice, or report side effects to the FDA at 1-800-FDA-1088.

Serious side effects and warnings

Opdivo may cause the following serious side effects:

Immune system problems

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 life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended, and may be more common when Opdivo is used in combination with other treatments. Call or see your healthcare provider right away if you develop any new or worsening symptoms, including:

• Lung problems new or worsening cough shortness of breath chest pain.
• Intestinal problems diarrhea (loose stools) or more bowel movements than usual stools that are black, tarry, sticky, or have blood or mucus severe stomach-area (abdomen) pain or tenderness.
• Liver problems yellowing of your skin or the whites of your eyes dark urine (tea colored) severe nausea or vomiting bleeding or bruising more easily than normal pain on the right side of your stomach area (abdomen).
• Hormone gland problems headaches that will not go away or unusual headaches urinating more often than usual hair loss eye sensitivity to light eye problems rapid heartbeat increased sweating extreme tiredness weight gain or weight loss feeling cold constipation your voice gets deeper dizziness or fainting changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness feeling more hungry or thirsty than usual.
• Kidney problems a decrease in the amount of urine swelling in your ankles blood in your urine loss of appetite.
• Skin problems rash itching skin blistering or peeling painful sores or ulcers in your mouth or in your nose, throat, or genital area fever or flu-like symptoms swollen lymph nodes.

Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with nivolumab. Call or see your healthcare provider right away for new or worsening symptoms, which may include:

• chest pain, irregular heartbeat, shortness of breath, swelling of ankles
• confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
• double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
• persistent or severe muscle pain or weakness, muscle cramps
• low red blood cells, bruising.

Rejection of a transplanted organ or tissue

Your healthcare provider should tell you what signs and symptoms you should report and monitor, depending on the type of organ or tissue transplant that you have had.

Complications in stem cell transplant recipients

Complications, including graft-versus-host disease (GVHD), may occur in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you undergo transplantation either before or after being treated with Opdivo. Your healthcare provider will monitor you for these complications.

Severe infusion-related reactions

Opdivo can cause severe infusion-related reactions. Tell your healthcare provider right away if you experience chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feeling like passing out, fever, or back or neck pain during or soon after your infusion.

Allergic reactions

Get emergency medical help if you have signs of an allergic reaction to Opdivo (hives, difficulty breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Notes:

Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with Opdivo. Your healthcare provider may treat you with corticosteroids or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with Opdivo if you have severe side effects.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Opdivo may cause harm to an unborn baby. Females who can get pregnant should use an adequate form of contraception while being treated with Opdivo.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Opdivo (nivolumab) helps the immune system to fight cancer. Some tumors produce proteins called PD-L1 and PD-L2 that bind to PD-1 receptors on T cells, essentially telling these immune cells to stand down. This prevents T cells from multiplying and attacking tumors. Nivolumab blocks this interaction by attaching to the PD-1 receptor, releasing the brakes on the immune system, and allowing T cells to recognize and fight cancer cells.

Opdivo (nivolumab) belongs to the drug class called immune checkpoint inhibitors. It may also be called a monoclonal antibody, PD-1-blocking antibody, or PD-1 inhibitor.

Your healthcare provider will give you Opdivo into your vein through an intravenous (IV) line over 30 minutes.

• When Opdivo is used alone, it is usually given every 2 weeks or 4 weeks, depending on the dose you are receiving.
• When Opdivo is used in combination with ipilimumab (except for treating NSCLC), Opdivo is usually given every 3 weeks, for up to 4 doses. Ipilimumab will be given on the same day. After that, Opdivo will be given alone every 2 weeks or 4 weeks, depending on the dose you are receiving.
• For NSCLC before surgery, Opdivo is given in combination with platinum-containing chemotherapy and another chemotherapy medicine every 3 weeks for 3 cycles. In some cases, Opdivo is used in combination with chemotherapy every 3 weeks for up to 4 cycles before you have surgery, followed by Opdivo used alone every 4 weeks after you have surgery for up to 1 year.
• For NSCLC that has spread to other parts of your body, when Opdivo is used in combination with ipilimumab, Opdivo is given every 3 weeks, and ipilimumab is given every 6 weeks for up to 2 years. Your healthcare provider will determine if you will also need to receive chemotherapy every 3 weeks for 2 cycles.
• For malignant pleural mesothelioma, Opdivo is given every 3 weeks, and ipilimumab is given every 6 weeks for up to 2 years.
• For RCC, when used in combination with cabozantinib, Opdivo is usually given every 2 weeks or 4 weeks, depending on the dose you are receiving. Cabozantinib is given once daily by mouth.
• For UC that has spread to other parts of your body or cannot be removed by surgery, when Opdivo is used in combination with chemotherapy medicines cisplatin and gemcitabine, Opdivo is given every 3 weeks for up to 6 cycles. Chemotherapy will be given on the same day. After that, Opdivo will be given alone every 2 weeks or 4 weeks, depending on the dose you are receiving.
• When Opdivo is used in combination with fluoropyrimidine- and platinum-containing chemotherapy for treating esophageal squamous cell carcinoma (ESCC), Opdivo is given either every 2 weeks or every 4 weeks, for up to 2 years.
• When Opdivo is used in combination with ipilimumab for ESCC, Opdivo is given every 2 weeks or 3 weeks, and ipilimumab is given every 6 weeks for up to 2 years.
• For gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, when used in combination with fluoropyrimidine- and platinum-containing chemotherapy, Opdivo is given every 2 weeks or 3 weeks, depending on the dose you are receiving, for up to 2 years. Chemotherapy will be given on the same day.

Your healthcare provider will decide how many treatments you need.

Your healthcare provider will do blood tests to check you for side effects.

If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Active ingredient: nivolumab

Inactive ingredients: mannitol, pentetic acid, polysorbate 80, sodium chloride, sodium citrate dihydrate, and Water for Injection. May contain hydrochloric acid and/or sodium hydroxide.

Available as a single-dose vial for intravenous infusion in the following strengths:

• 40 mg/4 mL (10 mg/mL)
• 100 mg/10 mL (10 mg/mL)
• 120 mg/12 mL (10 mg/mL)
• 240 mg/24 mL (10 mg/mL).

Opdivo (nivolumab) is manufactured by Bristol-Myers Squibb Company, Princeton, NJ 08543 USA U.S. License No. 1713.