Sacituzumab govitecan

Sacituzumab govitecan (brand name Trodelvy) is used to treat triple-negative breast cancer and hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer. It is given as an intravenous infusion by a healthcare provider.

Sacituzumab govitecan is a targeted anticancer treatment FDA-approved to treat adults with:

• triple-negative breast cancer that has spread (metastasized) or cannot be removed by surgery: as a first treatment, used alone, when you are not a candidate for PD-1 or PD-L1 inhibitor-based therapy as a first treatment, in combination with pembrolizumab (or pembrolizumab and berahyaluronidase alfa-pmph), when the tumor tests positive for PD-L1 as a second or later treatment, after at least 2 prior systemic therapies, including at least one for metastatic disease.
• hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer that has spread to nearby tissues (locally advanced) or other parts of the body (metastatic), when your HR-positive, HER2-negative breast cancer cannot be removed by surgery, and you have received hormonal-based therapy and at least 2 more therapies throughout the body (systemic) for metastatic breast cancer.

Sacituzumab govitecan (Trodelvy) received accelerated FDA approval for relapsed or refractory metastatic TNBC on April 22, 2020, which was converted to full approval on April 7, 2021. It gained full approval for metastatic HR+/HER2- breast cancer on February 3, 2023. No generic is available.

Sacituzumab govitecan (Trodelvy) is no longer approved for urothelial cancer.

Your healthcare provider will give you sacituzumab govitecan into your vein through an intravenous (IV) line.

• Sacituzumab govitecan is usually given 1 time each week, on Day 1 and Day 8 of a 21-day treatment cycle.
• You will receive the first dose of sacituzumab govitecan over 3 hours. If you tolerate the first dose well, future doses may be given over 1 to 2 hours.
• Before each dose of sacituzumab govitecan, you will receive medicines to help prevent infusion-related reactions, and nausea and vomiting.
• You will be monitored for side effects during and for at least 30 minutes after you receive each infusion of sacituzumab govitecan.
• Your healthcare provider may slow down or temporarily stop your infusion of sacituzumab govitecan if you have an infusion-related reaction or permanently stop sacituzumab govitecan if you have a life-threatening infusion-related reaction.
• Your healthcare provider will decide how long you will continue to receive sacituzumab govitecan.

Sacituzumab govitecan can cause serious side effects and has a Boxed Warning for neutropenia and diarrhea.

Low white blood cell count (neutropenia)

Low white blood cell counts can be severe and lead to infections that can be life-threatening or cause death as early as the first cycle of treatment. Your healthcare provider should check your blood cell counts during treatment with sacituzumab govitecan and may give a medicine to help prevent low white blood cell count starting in the first cycle of treatment if you have an increased risk for developing low white blood cell count with a fever (febrile neutropenia).

Tell your healthcare provider right away if you develop any of the following signs of infection during treatment with sacituzumab govitecan:

• fever
• chills
• cough
• shortness of breath
• burning or pain when you urinate.

Severe diarrhea

Severe diarrhea can lead to excessive loss of body fluids (dehydration) and kidney problems. Your healthcare provider should monitor you for diarrhea and give you medicine as needed to help control your diarrhea.

If you lose too much body fluid, your healthcare provider may need to give you fluids and electrolytes to replace body salts. If you develop diarrhea during treatment with sacituzumab govitecan, your healthcare provider should check to see if diarrhea may be caused by an infection.

Tell your healthcare provider right away:

• the first time that you get diarrhea during treatment with sacituzumab govitecan
• if you develop black or bloody stools
• if you develop symptoms of losing too much body fluid and body salts, such as lightheadedness, dizziness or faintness
• if you cannot take fluids by mouth due to nausea or vomiting
• if you cannot get your diarrhea under control within 24 hours.

Other serious side effects

Other serious side effects of sacituzumab govitecan include:

• Allergic and infusion-related reactions. Sacituzumab govitecan can cause serious or life-threatening allergic and infusion-related reactions. These reactions are more common within 24 hours of receiving sacituzumab govitecan. Tell your healthcare provider right away if you get any of the following symptoms of an allergic or infusion-related reaction during or at any time after your sacituzumab govitecan infusion: swelling of your face, lips, tongue, or throat hives skin rash, itching, or flushing of your skin fever difficulty breathing or wheezing lightheadedness, dizziness, feeling faint, or passing out chills or shaking chills (rigors) chest pain.
• Nausea and vomiting, which may be severe. Before each dose of sacituzumab govitecan, you will receive medicines to help prevent nausea and vomiting. You should be given medicines to take home with you, along with instructions about how to take them to help prevent and treat any nausea and vomiting after you receive sacituzumab govitecan. Tell your healthcare provider right away if you develop nausea or vomiting that is not controlled with the medicines prescribed for you.

Sacituzumab govitecan may cause fertility problems in females, which could affect your ability to have a baby. Talk to your healthcare provider if fertility is a concern for you.

It is not known if sacituzumab govitecan is safe and effective in children.

If you develop serious side effects, your healthcare provider may treat you with certain medicines, delay treatment, lower your dose, or permanently stop treatment with sacituzumab govitecan.

These are not all of the possible side effects of sacituzumab govitecan. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Common side effects

The most common side effects of sacituzumab govitecan when used alone include:

• decreased white blood cell counts
• decreased red blood cell counts
• nausea
• diarrhea
• feeling tired or weak
• hair loss
• increased sugar levels (glucose) in the blood
• constipation
• vomiting
• decreased protein levels (albumin) in the blood
• increased alkaline phosphatase levels in the blood
• decreased appetite
• stomach pain
• decreased creatinine clearance
• decreased magnesium and potassium levels in the blood.

The most common side effects of sacituzumab govitecan when used with pembrolizumab include:

• decreased white blood cell counts
• decreased red blood cell counts
• diarrhea
• nausea
• feeling tired or weak
• hair loss
• increased alkaline phosphatase levels in the blood
• increased sugar levels (glucose) in the blood
• increased liver enzyme levels in the blood
• constipation
• rash
• decreased potassium levels in the blood
• increased lactate dehydrogenase levels in the blood
• vomiting
• stomach pain
• headache
• increased eosinophil levels in the blood
• decreased protein levels (albumin) in the blood.

Sacituzumab govitecan-hziy is a targeted antibody-drug conjugate that delivers anticancer medicine into cells expressing Trop-2, a protein found in higher amounts on certain cancer cells than on normal cells.

It has three parts: sacituzumab, an antibody that targets Trop-2; SN-38, a topoisomerase I inhibitor and the active metabolite of irinotecan; and a linker joining the two. After binding to Trop-2-expressing cancer cells, the drug is taken into the cell, where the linker breaks apart and releases SN-38. SN-38 blocks topoisomerase I, causing single-strand breaks and DNA damage that lead to cell death and slowed tumor growth.

Do not receive sacituzumab govitecan if you have had a severe allergic reaction to sacituzumab govitecan, Trodelvy, or any inactive ingredients in the infusion.

Before receiving sacituzumab govitecan, tell your healthcare provider about all of your medical conditions, including if you:

• have been told that you carry a gene for uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28. People who carry this gene have an increased risk of getting side effects with sacituzumab govitecan, especially low white blood cell counts, a fever while your white blood cell count is low, and low red blood cell counts. See "Important information" above.
• have liver problems. It is not known if sacituzumab govitecan is safe in people with moderate or severe liver problems.
• are pregnant or plan to become pregnant. Sacituzumab govitecan can harm your unborn baby. Your healthcare provider should check to see if you are pregnant before you start receiving sacituzumab govitecan. Females who can become pregnant should use effective birth control during treatment and for 6 months after your last dose of sacituzumab govitecan. Talk to your healthcare provider about birth control choices that may be right for you during this time. Tell your healthcare provider right away if you become pregnant during treatment with sacituzumab govitecan. Males with a female partner who can become pregnant should use effective birth control during treatment and for 3 months after your last dose of sacituzumab govitecan.
• are breastfeeding or plan to breastfeed. It is not known if sacituzumab govitecan passes into your breast milk and can harm your baby. Do not breastfeed during treatment and for 1 month after your last dose of sacituzumab govitecan.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain medicines may affect the way sacituzumab govitecan works and may increase your risk of side effects.

Sacituzumab govitecan has been studied in several large clinical trials in breast cancer:

• ASCENT-03 (NCT05382299): In previously untreated metastatic triple-negative breast cancer (TNBC) in patients not candidates for PD-1 or PD-L1 inhibitor therapy, sacituzumab govitecan alone extended progression-free survival compared with chemotherapy (9.7 versus 6.9 months).
• ASCENT-04 (NCT05382286): In previously untreated, PD-L1-positive metastatic TNBC, sacituzumab govitecan plus pembrolizumab extended progression-free survival compared with chemotherapy plus pembrolizumab (11.2 versus 7.8 months).
• ASCENT (NCT02574455): In previously treated metastatic TNBC, sacituzumab govitecan improved progression-free survival (4.8 versus 1.7 months) and overall survival (11.8 versus 6.9 months) compared with chemotherapy.
• TROPiCS-02 (NCT03901339): In heavily pretreated HR-positive, HER2-negative metastatic breast cancer, sacituzumab govitecan improved progression-free survival (5.5 versus 4.0 months) and overall survival (14.4 versus 11.2 months) compared with chemotherapy.

Dose of sacituzumab govitecan for breast cancer as a single agent or in combination with pembrolizumab

• 10 mg/kg once weekly on Days 1 and 8 of 21-day treatment cycles until disease progression or unacceptable toxicity.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain medicines may affect the way sacituzumab govitecan works.

• Concomitant administration of UGT1A1 inhibitors such as flunitrazepam or propofol may increase the incidence of side effects due to a potential increase in systemic exposure to SN-38. Avoid co-administration.
• Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 Inducers such as phenytoin and phenobarbital. Avoid co-administration.

See the prescribing information for a full list of interactions.

Active ingredient: sacituzumab govitecan-hziy

Inactive ingredients: 2-(N-morpholino) ethane sulfonic acid (MES), polysorbate 80, and trehalose dihydrate

Sacituzumab govitecan is manufactured under the brand name Trodelvy by Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA 94404, USA. U.S. License No. 2258.