Trodelvy Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Trodelvy?

Trodelvy (sacituzumab govitecan-hziy) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate used to treat adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease.

What Are Side Effects of Trodelvy?

Trodelvy may cause serious side effects including:

hives,
difficulty breathing,
swelling of your face, lips, tongue, or throat,
dizziness,
lightheadedness,
itching,
sweating,
fever,
chills,
trouble breathing,
pain or burning when you urinate,
pale skin,
unusual tiredness,
lightheadedness,
shortness of breath,
cold hands and feet,
mouth sores,
skin sores,
sore throat,
cough,
diarrhea and diarrhea lasting longer than 24 hours,
black or bloody stools,
severe or ongoing vomiting, and
lightheadedness

Get medical help right away, if you have any of the symptoms listed above.

Side effects of Trodelvy include:

nausea,
low white blood cell count (neutropenia),
diarrhea,
fatigue,
anemia,
vomiting,
hair loss
constipation,
rash,
decreased appetite, and
abdominal pain

Call your doctor at once if you have the following serious side effects:

blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
low levels of sodium in the body with severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady; or
severe nervous system reaction with very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out.

Dosage for Trodelvy

The recommended dose of Trodelvy is 10 mg/kg once weekly on Days 1 and 8 of continuous 21-day treatment cycles until disease progression or unacceptable toxicity.

Trodelvy In Children

Safety and effectiveness of Trodelvy have not been established in pediatric patients.

What Drugs, Substances, or Supplements Interact with Trodelvy?

Trodelvy may interact with other medicines such as:

UGT1A1 inhibitors or inducers

Tell your doctor all medications and supplements you use.

Trodelvy During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Trodelvy; it may harm a fetus. Females of reproductive potential are advised to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Male patients with female partners of reproductive potential are advised to use effective contraception during treatment with Trodelvy and for 3 months after the last dose. There is no information regarding the presence of Trodelvy or SN-38 in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, breastfeeding is not recommended while using Trodelvy and for 1 month after the last dose.

Additional Information

Our Trodelvy (sacituzumab govitecan-hziy) for Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

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 FDA at 1-800-FDA-1088.

SLIDESHOW

Breast Cancer Awareness: Symptoms, Diagnosis, and Treatment See Slideshow

Trodelvy Consumer Information

This medicine can cause severe or life-threatening allergic reactions.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection or within 24 hours afterward. Tell your medical caregivers if you feel dizzy, light-headed, itchy, sweaty, or have a fever, chills, trouble breathing, or swelling in your face or throat.

You may get infections more easily, even serious or fatal infections. Call your doctor right away if you have signs of infection such as:

pain or burning when you urinate;
low red blood cells (anemia)--pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet; or
low white blood cell counts--fever, mouth sores, skin sores, sore throat, cough, trouble breathing.

Sacituzumab govitecan can cause severe diarrhea. Tell your doctor right away if you have:

diarrhea (the first time it occurs);
diarrhea lasting longer than 24 hours (even if you use anti-diarrhea medicine);
black or bloody stools;
severe or ongoing vomiting, especially if you can't keep liquids down; or
a light-headed feeling, like you might pass out.

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

Common side effects may include:

diarrhea, nausea, vomiting;
stomach pain, loss of appetite, constipation;
low blood cell counts;
rash;
hair loss; or
feeling tired.

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 FDA at 1-800-FDA-1088.

QUESTION

A lump in the breast is almost always cancer. See Answer

Trodelvy Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the label:

Neutropenia [see WARNINGS AND PRECAUTIONS]
Diarrhea [see WARNINGS AND PRECAUTIONS]
Hypersensitivity and Infusion-Related Reactions [see WARNINGS AND PRECAUTIONS]
Nausea and Vomiting [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The pooled safety population described in the Warnings and Precautions section reflect exposure to TRODELVY as a single agent in 795 patients from three studies, IMMU-132-01, IMMU-132-05 and IMMU-132-06 which included 366 patients with mTNBC who had received prior systemic chemotherapy for advanced disease and 180 patients with mUC. TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses of 10 mg/kg until disease progression or unacceptable toxicity. Among the 795 patients treated with TRODELVY, the median duration of treatment was 4.1 months (range: 0 to 59 months). In this pooled safety population, the most common (≥ 25%) adverse reactions were neutropenia (61%), nausea (66%), diarrhea (65%), fatigue (62%), alopecia (45%), anemia (42%), vomiting (39%), constipation (37%), decreased appetite (34%), rash (32%) and abdominal pain (28%).

Metastatic Triple-Negative Breast Cancer

ASCENT Study

The safety of TRODELVY was evaluated in a randomized, active-controlled, open-label trial (ASCENT) in patients with mTNBC who had previously received a taxane and at least two prior therapies. Patients were randomized (1:1) to receive either TRODELVY (n=258) or single agent chemotherapy (n=224) and were treated until disease progression or unacceptable toxicity [see Clinical Studies]. For patients treated with TRODELVY, the median duration of treatment was 4.4 months (range: 0 to 23 months).

Serious adverse reactions occurred in 27% of patients receiving TRODELVY. Serious adverse reactions in > 1% of patients receiving TRODELVY included neutropenia (7%), diarrhea (4%), and pneumonia (3%). Fatal adverse reactions occurred in 1.2% of patients who received TRODELVY, including respiratory failure (0.8%) and pneumonia (0.4%). TRODELVY was permanently discontinued for adverse reactions in 5% of patients. Adverse reactions leading to permanent discontinuation in ≥ 1 % of patients who received TRODELVY were pneumonia (1%) and fatigue (1%).

Adverse reactions leading to a treatment interruption of TRODELVY occurred in 63% of patients. The most frequent (≥5%) adverse reactions leading to a treatment interruption were neutropenia (47%), diarrhea (5%), respiratory infection (5%), and leukopenia (5%).

Adverse reactions leading to a dose reduction of TRODELVY occurred in 22% of patients. The most frequent (>4%) adverse reactions leading to a dose reduction were neutropenia (11%) and diarrhea (5%).

Granulocyte-colony stimulating factor (G-CSF) was used in 44% of patients who received TRODELVY.

Tables 2 and 3 summarize adverse reactions and select laboratory abnormalities, respectively, in the ASCENT study.

Table 2: Adverse Reactions in ≥10% of Patients with mTNBC in ASCENT TRODELVY (n=258) Single Agent Chemotherapy (n=224)

Adverse Reaction	TRODELVY (n=258)		Single Agent Chemotherapy (n=224)
Adverse Reaction	All Grades %	Grade 3 - 4 %	All Grades %	Grade 3 - 4 %
Blood and lymphatic system disorders
Neutropenia ^i.	64	52	44	34
Anemiaⁱⁱ	40	9	28	6
Leukopeniaⁱⁱⁱ	17	11	12	6
Lymphopenia^iv	10	2	6	2
Gastrointestinal disorders
Diarrhea	59	11	17	1
Nausea	57	3	26	0.4
Vomiting	33	2	16	1
Constipation	37	0.4	23	0
Abdominal Pain	30	3	12	1
Stomatitis^v	17	2	13	1
General disorders and administration site conditions
Fatigue^vi	65	6	50	9
Pyrexia	15	0.4	14	2
Infections and infestation
Urinary tract infection	13	0.4	8	0.4
Upper respiratory tract infection	12	0	3	0
Investigations
Alanine aminotransferase increased	11	1	10	1
Metabolism and nutrition disorders
Decreased appetite	28	2	21	1
Hypokalemia	16	3	13	0.4
Hypomagnesaemia	12	0	6	0
Musculoskeletal and connective tissue disorders
Back pain	16	1	14	2
Arthralgia	12	0.4	7	0
Nervous system disorders
Headache	18	0.8	13	0.4
Dizziness	10	0	7	0
Psychiatric disorders
Insomnia	11	0	5	0
Respiratory, thoracic and mediastinal disorders
Cough	24	0	18	0.4
Skin and subcutaneous tissue disorders
Alopecia	47	0	16	0
Rash	12	0.4	5	0.4
Pruritus	10	0	3	0
*Single agent chemotherapy included one of the following single-agents: eribulin (n=139), capecitabine (n=33), gemcitabine (n=38), or vinorelbine (except if patient had ≥Grade 2 neuropathy, n=52). Graded per NCI CTCAE v.5.0. ^i. Including neutropenia and neutrophil count decreased ^ii. Including anemia, hemoglobin decreased, and red blood cell count decreased ^iii. Including leukopenia and white blood cell count decreased ^iv. Including lymphopenia and lymphocyte count decreased ^v. Including stomatitis, glossitis, mouth ulceration, and mucosal inflammation ^vi. Including fatigue and asthenia

Table 3: Select Laboratory Abnormalities in >10% of Patients with mTNBC in ASCENT Laboratory Abnormality TRODELVY

ratory Abnormality	TRODELVY (n=258)		Single Agent Chemotherapy (n=224)
ratory Abnormality	All Gradess (%)	Grade 3 - 4 (%)	All Grades (%)	Grade 3 - 4 (%)
Decreased hemoglobin	94	9	57	6
Decreased leukocytes	86	41	53	25
Decreased neutrophils	78	49	48	36
Decreased lymphocytes	88	31	40	24
Decreased platelets	23	1.2	25	2.7

Study IMMU-132-01

The safety of TRODELVY was evaluated in a single-arm, open-label study (IMMU-132-01) in patients with mTNBC and other malignancies, which included 108 patients with mTNBC who had received at least two prior treatments for metastatic disease [see Clinical Studies]. TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses up to 10 mg/kg until disease progression or unacceptable toxicity. The median treatment duration in these 108 patients was 5.1 months (range: 0-51 months).

Serious adverse reactions occurred in 31% of the patients. Serious adverse reactions in >1% of patients receiving TRODELVY included febrile neutropenia (6%) vomiting (5%), nausea (3%), dyspnea (3%), diarrhea (4%), anemia (2%), pleural effusion, neutropenia, pneumonia, dehydration (each 2%).

TRODELVY was permanently discontinued for adverse reactions in 2% of patients. Adverse reactions leading to permanent discontinuation were anaphylaxis, anorexia/fatigue, headache (each 0.9%). Forty- five percent (45%) of patients experienced an adverse reaction leading to treatment interruption. The most common adverse reaction leading to treatment interruption was neutropenia (33%). Adverse reactions leading to dose reduction occurred in 33% of patients treated with TRODELVY, with 24% having one dose reduction, and 9% with two dose reductions. The most common adverse reaction leading to dose reductions was neutropenia/febrile neutropenia.

Adverse reactions occurring in ≥10% of patients with mTNBC in the IMMU-132-01 study are summarized in Table 4.

Table 4: Adverse Reactions in ≥ 10% of Patients with mTNBC in IMMU-132-01

Adverse Reaction	TRODELVY (n=108)
Adverse Reaction	Grade 1-4 (%)	Grade 3-4 (%)
Any adverse reaction	100	71
Gastrointestinal disorders	95	21
Nausea	69	6
Diarrhea	63	9
Vomiting	49	6
Constipation	34	1
Abdominal painⁱ	26	1
Mucositisⁱⁱ	14	1
General disorders and administration site conditions	77	9
Fatigueⁱⁱⁱ	57	8
Edema^iv	19	0
Pyrexia	14	0
Blood and lymphatic system disorders	74	37
Neutropenia	64	46
Neutropenia	52	12
Thrombocytopenia	14	3
Metabolism and nutrition disorders	58	22
Decreased appetite	30	1
Hyperglycemia	24	4
Hypomagnesemia	21	1
Hypokalemia	19	2
Hypophosphatemia	16	9
Dehydration	13	5
Skin and subcutaneous tissue disorders	63	4
Alopecia	38	0
Rash^v	31	3
Pruritus	17	0
Dry Skin	15	0
Nervous system disorders	56	4
Headache	23	1
Dizziness	22	0
Neuropathy^vi	24	0
Dysgeusia	11	0
Infections and infestations	55	12
Urinary Tract Infection	21	3
Respiratory Infection^vii	26	3
Musculoskeletal and connective tissue disorders	54	1
Back pain	23	0
Arthralgia	17	0
Pain in extremity	11	0
Respiratory, thoracic and mediastinal disorders	54	5
Cough^viii	22	0
Dyspnea^ix	21	3
Psychiatric disorders	26	1
Insomnia	13	0
Graded per NCI CTCAE v. 4.0 ^i. Including abdominal pain, distention, pain (upper), discomfort, tenderness. ⁱⁱ Including stomatitis, esophagitis, and mucosal inflammation ⁱⁱⁱ Including fatigue and asthenia. ^iv Including edema; and peripheral, localized, and periorbital edema ^v Including rash; maculopapular, erythematous, generalized rash; dermatitis acneiform; skin disorder, irritation, and exfoliation ^vi Including gait disturbance, hypoesthesia, muscular weakness, paresthesia, peripheral and sensory neuropathy ^vii Including lower and upper respiratory tract infection, pneumonia, influenza, viral upper respiratory infection, bronchitis and respiratory syncytial virus infection ^viii Includes cough and productive cough ^ix Includes dyspnea and exertional dyspnea

Table 5: Laboratory Abnormalities observed in ≥10% of Patients while receiving TRODELVY

Laboratory Abnormality	TRODELVY (n=108)
Laboratory Abnormality	All Grades (%)	Grade 3-4 (%)
Hematology
Decreased hemoglobin	93	6
Decreased leukocytes	91	26
Decreased neutrophils	82	32
Increased activated partial thromboplastin time	60	12
Decreased platelets	30	3
Chemistry
Increased alkaline phosphatase	57	2
Decreased magnesium	51	3
Decreased calcium	49	3
Increased glucose	48	3
Increased aspartate aminotransferase	45	3
Decreased albumin	39	1
Increased alanine aminotransferase	35	2
Decreased potassium	30	3
Decreased phosphate	29	5
Decreased sodium	25	4.7
Increased magnesium	24	4
Decreased glucose	19	2

Locally Advanced Or Metastatic Urothelial Cancer

Study IMMU-132-06

The safety of TRODELVY was evaluated in a single-arm, open-label study (IMMU-132-06) in patients (n=113) with mUC who had received previous platinum-based and anti-PD-1/PD-L1 therapy. TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses of 10 mg/kg until disease progression or unacceptable toxicity. (see Clinical Studies)

Serious adverse reactions occurred in 44% of patients. Serious adverse reactions in >1% of patients receiving TRODELVY included infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), sepsis or bacteremia (5%), diarrhea (4%), anemia, venous thromboembolism, and small intestinal obstruction (3% each), pneumonia, abdominal pain, pyrexia, and thrombocytopenia (2% each). Fatal adverse reactions occurred in 3.6% of patients, including sepsis, respiratory failure, epistaxis, and completed suicide.

TRODELVY was permanently discontinued for adverse reactions in 10% of patients. The most frequent adverse reaction leading to permanent discontinuation of study drug was neutropenia (4%, including febrile neutropenia in 2%). Adverse reactions leading to dose interruption occurred in 52% of patients. The most common adverse reactions leading to dose interruption were neutropenia (27%, including febrile neutropenia in 2%), infection (12%), and acute kidney injury (8%). Adverse reactions leading to a dose reduction of TRODELVY occurred in 42% of patients. The most common (>4%) adverse reactions leading to a dose reduction were neutropenia (13%, including febrile neutropenia in 3%), diarrhea (11%), fatigue (8%), and infection (4%). Granulocyte-colony stimulating factor (G-CSF) was used in 47% of patients who received TRODELVY.

The most common adverse reactions (incidence ≥25%) were: diarrhea, fatigue, neutropenia, nausea, alopecia, anemia, decreased appetite, constipation, vomiting, and abdominal pain.

Table 6: Adverse Reactions Reported in ≥15% (Grade 1-4) or ≥5% (Grade ≥3) of Patients Treated with TRODELVY in IMMU-132-06

Adverse Reaction	TRODELVY n=113
Adverse Reaction	Grade 1-4 %	Grade 3-4 %
Any	94	80
Gastrointestinal disorders
Diarrhea	72	12
Nausea	66	4
Constipation	34	1
Vomiting	34	1
Abdominal pain¹	31	2
General disorders and administration site conditions
Fatigue²	68	5
Pyrexia	19	0
Edema³	17	2
Skin and subcutaneous tissue disorders
Alopecia	49	0
Rash⁴	32	2
Metabolism and nutrition disorders
Decreased appetite	41	3
Weight loss⁵	17	2
Renal and urinary disorders
Acute kidney injury⁶	24	7
Hematuria	16	1
Infections and infestations
Any infection⁷	50	25
Urinary tract infection	19	12
Respiratory, thoracic and mediastinal disorders
Cough⁸	17	0
Dyspnea	16	0
Musculoskeletal
Back pain	16	0
Vascular disorders
Venous thromboembolism⁹	9	5
¹Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, gastrointestinal pain ²Includes fatigue and asthenia ³Includes edema genital, edema peripheral, peripheral swelling ⁴Includes dermatitis acneiform, dermatitis bullous, erythema, lichen planus, photosensitivity reaction, pruritus, pruritus generalised, rash, rash macular, rash maculo-papular, rash pruritic, skin papilloma, skin toxicity ⁵Includes failure to thrive and weight decreased ⁶Includes acute kidney injury, blood creatinine increased, nephropathy toxic, renal failure, renal impairment ⁷Includes bacteremia, body tinea, bronchitis, candida infection, cellulitis, clostridium difficile infection, corona virus infection, device related infection, diverticulitis, escherichia bacteremia, escherichia pyelonephritis, folliculitis, gastroenteritis, gastroenteritis escherichia coli, herpes zoster, kidney infection, klebsiella sepsis, lung infection, nasopharyngitis, oral candidiasis, oral herpes, pneumonia, pyelonephritis, pyelonephritis acute, respiratory tract infection, rhinitis, sepsis, sinusitis, skin infection, tooth abscess, upper respiratory tract infection, urinary tract infection, urosepsis, vascular device infection, viral infection, viral pharyngitis, vulvovaginal mycotic infection ⁸Includes cough, productive cough, upper-airway cough syndrome ⁹Includes deep vein thrombosis, embolism, and pulmonary embolism

Other clinically significant adverse reactions (≤15%) include: peripheral neuropathy (12%), sepsis or bacteremia (9%), and pneumonia (4%).

Table 7: Selected Laboratory Abnormalities Reported in ≥ 20% (Any Grade) or ≥ 5% (Grade 3-4) of Patients Treated with TRODELVY in IMMU-132-06

Adverse Reaction	TRODELVY n = 113
Adverse Reaction	Any Grade* %	Grade 3-4* %
Hematology
Leukocytes decreased	78	38
Lymphocytes decreased	71	35
Lymphocytes decreased	71	18
Neutrophils decreased	67	43
Platelets decreased	25	2
Chemistry
Glucose increased	59	8
Albumin decreased	51	4
Calcium decreased	46	9
Sodium decreased	43	1
Phosphate decreased	41	15
Alkaline phosphatase increased	36	0
Creatinine increased	32	5
Magnesium decreased	31	2
Alanine aminotransferase increased	28	2
Lactate dehydrogenase increased	28	0
Potassium decreased	27	0
Aspartate aminotransferase increased	26	2
Coagulation
Activated partial thromboplastin time increased	33	6
*Denominator for each laboratory parameter is based on the number of patients with a baseline and posttreatment laboratory value available (range: 66 to 111 patients).

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other sacituzumab govitecan products may be misleading.

The analysis of immunogenicity of TRODELVY in serum samples from 106 patients with mTNBC was evaluated using an electrochemiluminescence (ECL)-based immunoassay to test for anti-sacituzumab govitecan-hziy antibodies. Detection of the anti-sacituzumab govitecan-hziy antibodies was done using a 3-tier approach: screen, confirm, and titer. Persistent anti-sacituzumab govitecan-hziy antibodies developed in 2% (2/106) of patients.

DRUG INTERACTIONS

Effect Of Other Drugs On TRODELVY

UGT1A1 Inhibitors

Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38 [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Avoid administering UGT1A1 inhibitors with TRODELVY.

UGT1A1 Inducers

Exposure to SN-38 may be substantially reduced in patients concomitantly receiving UGT1A1 enzyme inducers [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Avoid administering UGT1A1 inducers with TRODELVY.

Read the entire FDA prescribing information for Trodelvy (Sacituzumab Govitecan-hziy for Injection, for IV Use)