Trodelvy

• TRODELVY can cause severe, life-threatening, or fatal neutropenia. Withhold TRODELVY for absolute neutrophil count below 1500/mm³ or neutropenic fever. Monitor blood cell counts periodically during treatment. Primary prophylaxis with G-CSF is recommended for all patients at increased risk of febrile neutropenia

  [see

  2.3 Dose Modifications for Adverse Reactions

  Management of adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of TRODELVY as described in Tables 1 and 2. Do not re-escalate the TRODELVY dose after a dose reduction for adverse reactions has been made.

  Table 1: Dosage Reduction Levels

  Dose Level	Dosage and Schedule
  Recommended starting dose	10 mg/kg once weekly on Days 1 and 8 of 21-day treatment cycles
  First dose reduction	Reduce to 7.5 mg/kg
  Second dose reduction	Reduce to 5 mg/kg
  Requirement for further dose reduction	Permanently discontinue TRODELVY

  The recommended dosage modifications for adverse reactions are provided in Table 2.

  Table 2: Dose Modifications for Adverse Reactions

  Adverse reactions	Severity	Dose Modification
  Neutropenia [see Warnings and Precautions (5.1)]	Grade 3–4 neutropenia (Absolute Neutrophil Count [ANC] <1000/mm3) or febrile neutropenia	Withhold TRODELVY until ANC ≥1500/mm3for Day 1 dose or ANC ≥1000/mm3for Day 8 Dose Administer G-CSF during treatment as clinically indicated. Reduce one dose level for each occurrence of febrile neutropenia or prolonged Grade 3–4 neutropenia, or discontinue according to Table 1.
  Nausea/Vomiting/ Diarrhea [see Warnings and Precautions (5.2, 5.4)]	Grade 3–4 nausea, vomiting or diarrhea that is not controlled with antiemetics or anti-diarrheal agents	Withhold TRODELVY until resolved to ≤ Grade 1 Reduce one dose level with each occurrence, or discontinue according to Table 1.
  Infusion-Related Reaction [see Warnings and Precautions (5.3)]	Grade 1–3 infusion-related reactions	Slow infusion rate or interrupt the infusion
  	Grade 4 infusion-related reactions	Discontinue TRODELVY.
  Other Toxicities	Other Grade 3–4 toxicities of any duration despite optimal medical management	Withhold TRODELVY until resolved to ≤ Grade 1 Reduce one dose level with each occurrence or discontinue according to Table 1.

  ]

  . Initiate anti-infective treatment in patient with febrile neutropenia without delay

  [see

  5.1 Neutropenia

  TRODELVY can cause severe, life-threatening, or fatal neutropenia as early as the first cycle of treatment. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3–4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6% of patients. The median time to first onset of neutropenia (including febrile neutropenia) was 16 days (range: 1 to 435 days). Neutropenia occurred earlier in patients with reduced UGT1A1 activity

  [see Warnings and Precautions (5.5)]

  . Neutropenic colitis occurred in 1.4% of patients.

  Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in all patients at increased risk of febrile neutropenia, including older patients, patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbidities.

  Monitor absolute neutrophil count (ANC) during treatment. Withhold TRODELVY for ANC below 1500/mm³on Day 1 of any cycle or below 1000/mm³on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Dose modifications may be required due to neutropenia. Treat neutropenia with G-CSF and administer prophylaxis in subsequent cycles as clinically indicated or indicated in Table 2

  [see Dosage and Administration (2.3)]

  .

  ].
• TRODELVY can cause severe diarrhea. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide

  [see

  5.2 Diarrhea

  TRODELVY can cause severe diarrhea. Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3–4 diarrhea occurred in 11% of all patients treated with TRODELVY. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients.

  Withhold TRODELVY for Grade 3–4 diarrhea at the time of scheduled treatment administration and resume when resolved to ≤ Grade 1

  [see Dosage and Administration (2.3)].

  At the onset of diarrhea, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated.

  Patients who exhibit an excessive cholinergic response to treatment with TRODELVY (e.g., abdominal cramping, diarrhea, salivation, etc.) can receive appropriate premedication (e.g., atropine) for subsequent treatments.

  ].

  If severe diarrhea occurs, withhold TRODELVY until resolved to
  ≤
  Grade 1 and reduce subsequent doses

  [see

  2.3 Dose Modifications for Adverse Reactions

  Management of adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of TRODELVY as described in Tables 1 and 2. Do not re-escalate the TRODELVY dose after a dose reduction for adverse reactions has been made.

  Table 1: Dosage Reduction Levels

  Dose Level	Dosage and Schedule
  Recommended starting dose	10 mg/kg once weekly on Days 1 and 8 of 21-day treatment cycles
  First dose reduction	Reduce to 7.5 mg/kg
  Second dose reduction	Reduce to 5 mg/kg
  Requirement for further dose reduction	Permanently discontinue TRODELVY

  The recommended dosage modifications for adverse reactions are provided in Table 2.

  Table 2: Dose Modifications for Adverse Reactions

  Adverse reactions	Severity	Dose Modification
  Neutropenia [see Warnings and Precautions (5.1)]	Grade 3–4 neutropenia (Absolute Neutrophil Count [ANC] <1000/mm3) or febrile neutropenia	Withhold TRODELVY until ANC ≥1500/mm3for Day 1 dose or ANC ≥1000/mm3for Day 8 Dose Administer G-CSF during treatment as clinically indicated. Reduce one dose level for each occurrence of febrile neutropenia or prolonged Grade 3–4 neutropenia, or discontinue according to Table 1.
  Nausea/Vomiting/ Diarrhea [see Warnings and Precautions (5.2, 5.4)]	Grade 3–4 nausea, vomiting or diarrhea that is not controlled with antiemetics or anti-diarrheal agents	Withhold TRODELVY until resolved to ≤ Grade 1 Reduce one dose level with each occurrence, or discontinue according to Table 1.
  Infusion-Related Reaction [see Warnings and Precautions (5.3)]	Grade 1–3 infusion-related reactions	Slow infusion rate or interrupt the infusion
  	Grade 4 infusion-related reactions	Discontinue TRODELVY.
  Other Toxicities	Other Grade 3–4 toxicities of any duration despite optimal medical management	Withhold TRODELVY until resolved to ≤ Grade 1 Reduce one dose level with each occurrence or discontinue according to Table 1.

  ].

TRODELVY is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

• Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. (
  1.1 Locally Advanced or Metastatic Breast Cancer

  • TRODELVY is indicated for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
  • TRODELVY is indicated for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
  ,
  14.1 Locally Advanced or Metastatic Triple-Negative Breast Cancer

  ASCENT

  Efficacy was evaluated in a multicenter, open-label, randomized study (ASCENT; NCT02574455) conducted in 529 patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who had relapsed after at least two prior chemotherapies for breast cancer (one of which could be in the neoadjuvant or adjuvant setting provided progression occurred within a 12 month period). All patients received previous taxane treatment in either the adjuvant, neoadjuvant, or advanced stage unless there was a contraindication or intolerance to taxanes during or at the end of the first taxane cycle. Magnetic resonance imaging (MRI) to determine brain metastases was required prior to enrollment for patients with known or suspected brain metastases. Patients with brain metastases were allowed to enroll up to a pre-defined maximum of 15% of patients in the ASCENT study. Patients with known Gilbert's disease or bone-only disease were excluded.

  Patients were randomized (1:1) to receive TRODELVY 10 mg/kg as an intravenous infusion on Days 1 and 8 of a 21-day (n=267) or physician's choice of single agent chemotherapy (n=262). Single agent chemotherapy was determined by the investigator before randomization from one of the following choices: eribulin (n=139), capecitabine (n=33), gemcitabine (n=38), or vinorelbine (n=52).

  Patients were treated until disease progression or unacceptable toxicity. The major efficacy outcome was progression-free survival (PFS) in patients without brain metastases at baseline (i.e., BMNeg) as measured by a blinded, independent, centralized review assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Additional efficacy measures included PFS for the full population (all patients with and without brain metastases) and overall survival (OS).

  The median age of patients in the full population (n = 529) was 54 years (range: 27 to 82 years); 99.6% were female; 79% were White, 12% were Black/African American; and 81% of patients were < 65 years of age. All patients had an ECOG performance status of 0 (43%) or 1 (57%). Forty-two percent of patients had hepatic metastases, 9% were BRCA1/BRCA2 mutational status positive, and 70% were TNBC at diagnosis. Twelve percent had baseline brain metastases previously treated and stable (n=61; 32 on TRODELVY arm and 29 on single agent chemotherapy arm). Overall, 29% of patients had received prior PD-1/PD-L1 therapy. Thirteen percent of patients in the TRODELVY group in the full population received only 1 prior line of systemic therapy in the metastatic setting.

  The efficacy results are summarized in Table 10 and are shown in Figure 1 and Figure 2. Efficacy results for the subgroup of patients who had received only 1 prior line of systemic therapy in the metastatic setting (in addition to having disease recurrence or progression within 12 months of neoadjuvant/adjuvant systemic therapy) were consistent with those who had received at least two prior lines in the metastatic setting.

  Table 10: Efficacy Results from ASCENT

  	All Randomized Patients
  	TRODELVY n=267	Single Agent Chemotherapy n=262
  CI = Confidence Interval
  Progression-Free SurvivalPFS is defined as the time from the date of randomization to the date of the first radiological disease progression or death due to any cause, whichever comes first.per BICR
  Disease Progression or Death (%)	190 (71%)	171 (65%)
  Median PFS in months (95% CI)	4.8 (4.1, 5.8)	1.7 (1.5, 2.5)
  Hazard ratioStratified log-rank test adjusted for stratification factors: number of prior chemotherapies, presence of known brain metastases at study entry, and region.(95% CI)	0.43 (0.35, 0.54)
  p-value	<0.0001
  Overall Survival
  Deaths (%)	179 (67%)	206 (79%)
  Median OS in months (95% CI)	11.8 (10.5, 13.8)	6.9 (5.9, 7.6)
  Hazard ratio (95% CI)	0.51 (0.41, 0.62)
  p-value	<0.0001

  Figure 1: Kaplan-Meier Plot of PFS by BICR (All Randomized Patients) in ASCENT

  

  Figure 2: Kaplan-Meier Plot of OS (All Randomized Patients) in ASCENT

  

  An exploratory analysis of PFS in patients with previously treated, stable brain metastases showed a stratified HR of 0.65 (95% CI: 0.35, 1.22). The median PFS in the TRODELVY arm was 2.8 months (95% CI: 1.5, 3.9) and the median PFS with single agent chemotherapy was 1.6 months (95% CI: 1.3, 2.9). Exploratory OS analysis in the same population showed a stratified HR of 0.87 (95% CI: 0.47, 1.63). The median OS in the TRODELVY arm was 6.8 months (95% CI: 4.7, 14.1) and the median OS with single agent chemotherapy was 7.4 months (95% CI: 4.7, 11.1).

  Figure 1

  Figure 2

  IMMU-132-01

  The efficacy of TRODELVY was evaluated in a multicenter, single-arm, study (NCT01631552) that enrolled 108 patients with metastatic triple-negative breast cancer (mTNBC) who had received at least two prior anticancer therapies for metastatic disease. Patients with bulky disease, defined as a mass > 7 cm, were not eligible. Patients with treated brain metastases not receiving high dose steroids (> 20 mg prednisone or equivalent) for at least four weeks were eligible. Patients with known Gilbert's disease were excluded.

  Patients received TRODELVY 10 mg/kg intravenously on Days 1 and 8 of a 21-day treatment cycle. Patients were treated with TRODELVY until disease progression or intolerance to the therapy. Tumor imaging was obtained every 8 weeks, with confirmatory CT/MRI scans obtained 4–6 weeks after an initial partial or complete response, until progression requiring treatment discontinuation. Major efficacy outcome measures were investigator assessed overall response rate (ORR) using RECIST 1.1 and duration of response.

  The median age was 55 years (range: 31 to 80 years); 87% of patients were younger than 65 years. The majority of patients were female (99%) and White (76%). At study entry, all patients had an ECOG performance status of 0 (29%) or 1 (71%). Seventy-six percent had visceral disease, 42% had hepatic metastases, 56% had lung/pleura metastases, and 2% had brain metastases. Twelve patients (11%) had Stage IV disease at the time of initial diagnosis.

  The median number of prior systemic therapies received in the metastatic setting was 3 (range: 2 to 10). Prior chemotherapies in the metastatic setting included carboplatin or cisplatin (69%), gemcitabine (55%), paclitaxel or docetaxel (53%), capecitabine (51%), eribulin (45%), doxorubicin (24%), vinorelbine (16%), cyclophosphamide (19%), and ixabepilone (8%).

  Overall, 98% of patients had received prior taxanes and 86% had received prior anthracyclines either in the (neo)adjuvant or metastatic setting.

  Table 11 summarizes the efficacy results.

  Table 11: Efficacy results for patients with mTNBC in IMMU-132-01

  	TRODELVY (N=108)
  CI: confidence interval
  +: denotes ongoing
  Overall Response Rateinvestigator assessment
  ORR (95% CI)	33.3% (24.6, 43.1)
  Complete response	2.8%
  Partial response	30.6%
  Response duration
  Number of responders	36
  Median, Months (95% CI)	7.7 (4.9, 10.8)
  Range, Months	1.9+, 30.4+
  % with duration ≥ 6 months	55.6%
  % with duration ≥ 12 months	16.7%
  )
• Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. (
  1.1 Locally Advanced or Metastatic Breast Cancer

  • TRODELVY is indicated for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
  • TRODELVY is indicated for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
  ,
  14.2 Locally Advanced or Metastatic HR-Positive, HER2-Negative Breast Cancer

  TROPiCS-02 Study

  The efficacy of TRODELVY was evaluated in a multicenter, open label, randomized study (TROPiCS-02; NCT03901339) conducted in 543 patients with unresectable locally advanced or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer whose disease has progressed after the following in any setting: a CDK 4/6 inhibitor, endocrine therapy, and a taxane; patients received at least two prior chemotherapies in the metastatic setting (one of which could be in the neoadjuvant or adjuvant setting if recurrence occurred within 12 months).

  Patients were randomized (1:1) to receive TRODELVY 10 mg/kg as an intravenous infusion on Days 1 and 8 of a 21 day cycle (n=272) or single agent chemotherapy (n=271). Single agent chemotherapy was determined by the investigator before randomization from one of the following choices: eribulin (n=130), vinorelbine (n=63), gemcitabine (n=56), or capecitabine (n=22). Randomization was stratified by the following factors: prior chemotherapy regimens for metastatic disease (2 vs. 3–4), visceral metastasis (Yes or No), and endocrine therapy in the metastatic setting for at least 6 months (Yes or No).

  Patients were treated until disease progression or unacceptable toxicity. Administration of TRODELVY was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered by the investigator to be deriving clinical benefit. The primary efficacy outcome measure was PFS as determined by BICR per RECIST v1.1. Additional efficacy measures included OS, ORR by BICR, and DOR by BICR.

  The median age of patients in the study population was 56 years (range: 27–86 years), 26% of patients were 65 years or over. The majority of patients were female (99%); 67% were White, 4% were Black and 3% were Asian, and 26% were of unknown race. Patients received a median of 7 (range: 3 to 17) prior systemic regimens in any setting and 3 (range: 0 to 8) prior systemic chemotherapy regimens in the metastatic setting. Approximately 42% of patients had 2 prior chemotherapy regimens for treatment of metastatic disease compared to 58% of patients who had 3 to 4 prior chemotherapy regimens and all patients had an ECOG performance status of 0 (45%) or 1 (55%). Ninety-five percent of patients had visceral metastases. Most patients received endocrine therapy in the metastatic setting for ≥ 6 months (86%).

  TRODELVY demonstrated a statistically significant improvement in PFS and OS versus single agent chemotherapy.

  The efficacy results are summarized in Table 12 and Figure 3 and Figure 4.

  Table 12: Efficacy Results from TROPiCS-02

  	All Randomized Patients
  	TRODELVY n=272	Single Agent Chemotherapy n=271
  Progression-Free Survival by BICRPFS is defined as the time from the date of randomization to the date of the first radiological disease progression or death due to any cause, whichever comes first.
  Median PFS in months (95% CI)	5.5 (4.2, 7.0)	4.0 (3.1, 4.4)
  Hazard ratio (95% CI)	0.661 (0.529, 0.826)
  p-valueStratified log-rank test adjusted for stratification factors: prior chemotherapy regimens for metastatic disease (2 vs. 3–4), visceral metastasis (Y/N), and endocrine therapy in the metastatic setting for at least 6 months (Yes or No). BICR = Blinded Independent Central Review; CI = Confidence Interval	0.0003
  Overall SurvivalSecond interim OS analysis (conducted when 390 OS events were observed)
  Median OS in months (95% CI)	14.4 (13.0, 15.7)	11.2 (10.1, 12.7)
  Hazard ratio (95% CI)	0.789 (0.646, 0.964)
  p-value	0.0200
  Objective Response Rate by BICR
  Response Rate, % (95% CI)	21.0 (16.3, 26.3)	14.0 (10.1, 18.7)
  Odds ratio (95% CI)	1.625 (1.034, 2.555)
  p-value	0.0348
  Duration of Response (DOR) by BICR
  Median DOR in months (95% CI)	8.1 (6.7, 9.1)	5.6 (3.8, 7.9)

  Figure 3: Kaplan-Meier Plot of PFS by BICR in TROPiCS-02

  

  Figure 4: Kaplan-Meier Plot of OS in TROPiCS-02

  

  Figure 3

  Figure 4

  )

• Do NOT substitute TRODELVY for or use with other drugs containing irinotecan or its active metabolite SN-38. (
  2.1 Important Use Information

  Do NOT substitute TRODELVY for or use with other drugs containing irinotecan or its active metabolite SN-38.
  )
• For intravenous infusion only. Do not administer as an intravenous push or bolus.
• The recommended dose is 10 mg/kg once weekly on Days 1 and 8 of continuous 21-day treatment cycles until disease progression or unacceptable toxicity. (
  2.2 Recommended Dosage

  The recommended dosage 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.

  • Premedicate with antipyretics, H1 and H2 blockers prior to infusion, and corticosteroids may be used for patients who had prior infusion reactions.
  • Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK₁receptor antagonist, as well as other drugs as indicated).

  Prophylaxis for Neutropenia

  Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is recommended starting in the first cycle for all patients at increased risk of febrile neutropenia

  [see Warnings and Precautions (5.1)]

  .
  )
• Premedication for prevention of infusion reactions and prevention of chemotherapy-induced nausea and vomiting is recommended. (
  2.2 Recommended Dosage

  The recommended dosage 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.

  • Premedicate with antipyretics, H1 and H2 blockers prior to infusion, and corticosteroids may be used for patients who had prior infusion reactions.
  • Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK₁receptor antagonist, as well as other drugs as indicated).

  Prophylaxis for Neutropenia

  Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is recommended starting in the first cycle for all patients at increased risk of febrile neutropenia

  [see Warnings and Precautions (5.1)]

  .
  )
• Primary prophylaxis with G-CSF is recommended starting in the first cycle in all patients at increased risk of febrile neutropenia. (
  2.2 Recommended Dosage

  The recommended dosage 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.

  • Premedicate with antipyretics, H1 and H2 blockers prior to infusion, and corticosteroids may be used for patients who had prior infusion reactions.
  • Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK₁receptor antagonist, as well as other drugs as indicated).

  Prophylaxis for Neutropenia

  Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is recommended starting in the first cycle for all patients at increased risk of febrile neutropenia

  [see Warnings and Precautions (5.1)]

  .
  )
• Monitor patients during the infusion and for at least 30 minutes after completion of infusion. Treatment interruption and/or dose reduction may be needed to manage adverse reactions. (
  2.2 Recommended Dosage

  The recommended dosage 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.

  • Premedicate with antipyretics, H1 and H2 blockers prior to infusion, and corticosteroids may be used for patients who had prior infusion reactions.
  • Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK₁receptor antagonist, as well as other drugs as indicated).

  Prophylaxis for Neutropenia

  Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is recommended starting in the first cycle for all patients at increased risk of febrile neutropenia

  [see Warnings and Precautions (5.1)]

  .
  )
• See Full Prescribing Information for preparation and administration instructions. (
  2.4 Preparation and Administration

  Reconstitution

  • TRODELVY is a hazardous drug.
  • Follow applicable special handling and disposal procedures¹.
  • Calculate the required dose (mg) of TRODELVY based on the patient's current body weight

    [see Dosage and Administration (2.2)]

    .
  • Using a sterile syringe, slowly inject 20 mL of 0.9% Sodium Chloride Injection, USP, into each 180 mg TRODELVY vial. Each vial contains overfill to compensate for liquid loss during preparation and after reconstitution, the total resulting volume delivers a
    concentration of 10 mg/mL
    .
  • Gently swirl vials and allow to dissolve for up to 15 minutes. Do not shake. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be free of visible particulates, clear and yellow. Do not use the reconstituted solution if it is cloudy or discolored.
  • Use immediately to prepare a diluted TRODELVY infusion solution.

  Dilution

  • Calculate the required amount of the reconstituted TRODELVY solution needed to obtain the appropriate dose according to the patient's body weight.
  • Determine the final volume of the infusion solution to deliver the appropriate dose at a TRODELVY concentration range of 1.1 mg/mL to 3.4 mg/mL.
  • Use 0.9% Sodium Chloride Injection, USP only since the stability of the reconstituted TRODELVY solution has not been determined with other infusion-based solutions. Use a polyvinyl chloride, polypropylene/polyethylene, polyolefin, or ethylene vinyl acetate infusion bag.
  • Withdraw and discard the volume of 0.9% Sodium Chloride Injection, USP from the final infusion bag that is necessary to achieve the indicated TRODELVY concentration following the addition of the calculated amount of reconstituted TRODELVY solution.
  • Withdraw the calculated amount of the reconstituted TRODELVY solution from the vial(s) using a syringe. Discard any unused portion remaining in the vial(s).
  • To minimize foaming, slowly inject the calculated amount of reconstituted TRODELVY solution into the infusion bag. Do not shake the contents.
  • If not used immediately, the infusion bag containing TRODELVY solution can be stored refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours protected from light. After refrigeration, administer diluted solution at room temperature up to 25°C (77°F) within 8 hours (including infusion time).

  Do Not Freeze or Shake.

  Administration

  • Administer TRODELVY as an intravenous infusion. Protect infusion bag from light. The infusion bag should be covered during administration to the patient until dosing is complete. It is not necessary to cover the infusion tubing or to use light-protective tubing during the infusion.
  • An infusion pump may be used.
  • Do not mix TRODELVY, or administer as an infusion, with other medicinal products.
  • Upon completion of the infusion, flush the intravenous line with 20 mL 0.9% Sodium Chloride Injection, USP.
  )

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

• Lactation: Advise not to breastfeed. (
  8.2 Lactation

  Risk Summary

  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.
  )