INDICATION & DOSING

WARNING: NEUTROPENIA AND DIARRHEA

  • Severe neutropenia may occur. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay [see Warnings and Precautions (5.1)].
  • Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide [see Warnings and Precautions (5.2)]. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤ Grade 1 and reduce subsequent doses [see Dosage and Administration (2.3)].

1INDICATIONS AND USAGE

TRODELVY is indicated for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease.

This indication is approved under accelerated approval based on tumor response rate and duration of response [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

2DOSAGE AND ADMINISTRATION

2.1 Important Use Information

Do NOT substitute TRODELVY for or use with other drugs containing irinotecan or its active metabolite SN-38.

2.2 Recommended Dose and Schedule

The recommended dose of TRODELVY is 10 mg/kg administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles. Continue treatment until disease progression or unacceptable toxicity. Do not administer TRODELVY at doses greater than 10 mg/kg.

Administer TRODELVY as an intravenous infusion only. Do not administer as an intravenous push or bolus.

First infusion: Administer infusion over 3 hours. Observe patients during the infusion and for at least 30 minutes following the initial dose, for signs or symptoms of infusion-related reactions [see Warning and Precautions (5.3)].

Subsequent infusions: Administer infusion over 1 to 2 hours if prior infusions were tolerated. Observe patients during the infusion and for at least 30 minutes after infusion.

Premedication

Prior to each dose of TRODELVY, premedication for prevention of infusion reactions and prevention of chemotherapy-induced nausea and vomiting (CINV) is recommended.

2.3 Dose Modifications for Adverse Reactions

Infusion-related Reactions

Slow or interrupt the infusion rate of TRODELVY if the patient develops an infusion-related reaction. Permanently discontinue TRODELVY for life-threatening infusion-related reactions [see Warning and Precautions (5.3)]

Dose Modifications for Adverse Reactions

Withhold or discontinue TRODELVY to manage adverse reactions as described in Table 1. Do not re-escalate the TRODELVY dose after a dose reduction for adverse reactions has been made.

Table 1: Dose Modifications for Adverse Reactions
Adverse ReactionOccurrenceDose Modification
Severe Neutropenia [see Warning and Precautions (5.1)]
Grade 4 neutropenia ≥7 days,
OR
Grade 3 febrile neutropenia
(absolute neutrophil count <1000/mm3 and fever ≥38.5°C),
OR
At time of scheduled treatment, Grade 3-4 neutropenia which delays dosing by 2 or 3 weeks for recovery to ≤ Grade 1
First25% dose reduction and administer granulocyte-colony stimulating factor (G‑CSF)
Second50% dose reduction
ThirdDiscontinue treatment
At time of scheduled treatment, Grade 3-4 neutropenia which delays dosing beyond 3 weeks for recovery to ≤ Grade 1FirstDiscontinue treatment
Severe Non-Neutropenic Toxicity

Grade 4 non-hematologic toxicity of any duration,

OR

Any Grade 3-4 nausea, vomiting or diarrhea due to treatment that is not controlled with antiemetics and anti-diarrheal agents [see Warning and Precautions (5.2), (5.4)],

OR

Other Grade 3-4 non-hematologic toxicity persisting >48 hours despite optimal medical management,

OR
At time of scheduled treatment, Grade 3-4 non-neutropenic hematologic or non-hematologic toxicity, which delays dose by 2 or 3 weeks for recovery to ≤ Grade 1
First25% dose reduction
Second50% dose reduction
ThirdDiscontinue treatment
In the event of Grade 3-4 non-neutropenic hematologic or non-hematologic toxicity, which does not recover to ≤ Grade 1 within 3 weeksFirstDiscontinue treatment

2.4 Preparation for Administration

Reconstitution

Dilution

Do Not Freeze or Shake. Protect from Light.

Administration

3DOSAGE FORMS AND STRENGTHS

For injection: 180 mg off-white to yellowish lyophilized powder in a single-dose vial.

Next: Safety
INDICATION

TRODELVY™ (sacituzumab govitecan-hziy) is indicated for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION
WARNING: NEUTROPENIA AND DIARRHEA

Severe neutropenia may occur. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.

Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤Grade 1 and reduce subsequent doses.

Contraindications

TRODELVY is contraindicated in patients who have experienced a severe hypersensitivity reaction to TRODELVY.

Hypersensitivity

TRODELVY can cause severe and life-threatening hypersensitivity. Anaphylactic reactions have been observed in clinical trials with TRODELVY.

Hypersensitivity reactions within 24 hours of dosing occurred in 37% (151/408) of patients treated with TRODELVY. Grade 3-4 hypersensitivity occurred in 1% (6/408) of patients treated with TRODELVY. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 1% (3/408).

Pre-infusion medication for patients receiving TRODELVY is recommended. Observe patients closely for infusion-related reactions during each TRODELVY infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use.

Nausea and Vomiting

TRODELVY is emetogenic. Nausea occurred in 69% (74/108) of patients with mTNBC and 69% (281/408) of all patients treated with TRODELVY. Grade 3 nausea occurred in 6% (7/108) and 5% (22/408) of these populations, respectively.

Vomiting occurred in 49% (53/108) of patients with mTNBC and 45% (183/408) of all patients treated with TRODELVY. Grade 3 vomiting occurred in 6% (7/108) and 4% (16/408) of these patients, respectively.

Premedicate with a two or three drug combination regimen (e.g. dexamethasone with either a 5-HT3 receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV).

Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting at the time of scheduled treatment administration and resume with additional supportive measures when resolved to Grade ≤1.

Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Use in Patients with Reduced UGT1A1 Activity

Individuals who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia and may be at increased risk for other adverse reactions following initiation of TRODELVY treatment.

In 84% (343/408) of patients who received TRODELVY (up to 10 mg/kg on Days 1 and 8 of a 21-day cycle) and had retrospective UGT1A1 genotype results available, the incidence of Grade 4 neutropenia was 26% (10/39) in patients homozygous for the UGT1A1*28 allele, 13% (20/155) in patients heterozygous for the UGT1A1*28 allele and 11% (16/149) in patients homozygous for the wild-type allele.

Closely monitor patients with reduced UGT1A1 activity for severe neutropenia. The appropriate dose for patients who are homozygous for UGT1A1*28 is not known and should be considered based on individual patient tolerance to treatment.

Embryo-Fetal Toxicity

Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose.

Lactation

There is no information regarding the presence of sacituzumab govitecan-hziy 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, advise women not to breastfeed during treatment and for 1 month after the last dose of TRODELVY.

Adverse Reactions

Most common adverse reactions (incidence ≥25%) in patients with mTNBC are nausea (69%), neutropenia (64%), diarrhea (63%), fatigue (57%), anemia (52%), vomiting (49%), alopecia (38%), constipation (34%), rash (31%), decreased appetite (30%), abdominal pain (26%), and respiratory infection (26%).

Please see full Prescribing Information, including boxed Warning, and Patient Information.