April 13, 2021 – Sacituzumab govitecan (TRODELVY, Immunomedics Inc.) for advanced urothelial cancer.

April 7, 2021 – Sacituzumab govitecan (TRODELVY, Immunomedics Inc.) for 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.

April 22, 2020 - Sacituzumab govitecan-hziy (TRODELVY, Immunomedics, Inc.) for adult patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease (with Pharmacist’s Applications to Practice).

April 13, 2021

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761115s009lbl.pdf

On April 13, 2021, the Food and Drug Administration granted accelerated approval to sacituzumab govitecan (TRODELVY, Immunomedics Inc.) for patients with locally advanced or metastatic urothelial cancer (mUC) who previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor.

Efficacy and safety were evaluated in TROPHY (IMMU-132-06; NCT03547973), a single-arm, multicenter trial that enrolled 112 patients with locally advanced or mUC who received prior treatment with a platinum-containing chemotherapy and either a PD-1 or PD-L1 inhibitor. Patients received sacituzumab govitecan, 10 mg/kg intravenously, on days 1 and 8 of a 21-day treatment cycle.

The main efficacy endpoints were objective response rate (ORR) and duration of response (DOR), evaluated by independent review using RECIST 1.1 criteria. The confirmed ORR was 27.7% (95% CI:19.6, 36.9) with 5.4% complete responses and 22.3% partial responses. The median DOR was 7.2 months (n=31; 95% CI: 4.7, 8.6; range 1.4+, 13.7).

Most common adverse reactions (incidence >25%) in patients receiving sacituzumab govitecan are neutropenia, nausea, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, decreased appetite, rash, and abdominal pain.

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

View full prescribing information for Trodelvy.

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 a confirmatory trial.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 6 weeks ahead of the FDA goal date.

This application was granted priority review and fast track designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email This email address is being protected from spambots. You need JavaScript enabled to view it..

April 7, 2021

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761115s005s013lbl.pdf

On April 7, 2021, the Food and Drug Administration granted regular approval to sacituzumab govitecan (TRODELVY, Immunomedics Inc.) for 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.

In April 2020, sacituzumab govitecan received accelerated approval for patients with mTNBC who have received at least two prior therapies for metastatic disease. The following trial was the confirmatory trial for the accelerated approval.

Efficacy and safety were evaluated in a multicenter, open-label, randomized trial (ASCENT; NCT02574455) conducted in 529 patients with unresectable locally advanced or mTNBC who had relapsed after at least two prior chemotherapies, one of which could be in the neoadjuvant or adjuvant setting, if progression occurred within 12 months. Patients were randomized (1:1) to receive sacituzumab govitecan, 10 mg/kg as an intravenous infusion, on days 1 and 8 of a 21-day (n=267) cycle or physician’s choice of single agent chemotherapy (n=262).

The primary  efficacy endpoint was progression-free survival (PFS) in patients without brain metastases at baseline as measured by a blinded, independent, centralized review assessed using RECIST 1.1 criteria. Additional efficacy endpoints included PFS for the full population (with and without brain metastases) and overall survival (OS).

Among all randomized patients (with and without brain metastases), median PFS for patients receiving sacituzumab govitecan was 4.8 months (95% CI: 4.1, 5.8) compared with 1.7 months (95% CI: 1.5, 2.5) in those  receiving chemotherapy (HR 0.43; 95% CI: 0.35, 0.54; p<0.0001). Median OS was 11.8 months (95% CI: 10.5, 13.8) and 6.9 months (95% CI: 5.9, 7.6) respectively (HR 0.51; 95% CI: 0.41, 0.62; p<0.0001).

Most common adverse reactions (incidence >25%) in patients receiving sacituzumab govitecan are nausea, neutropenia, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, rash, decreased appetite, and abdominal pain.

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

View full prescribing information for Trodelvy.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies. 

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 6 weeks ahead of the FDA goal date.

This application was granted priority review and breakthrough designation . A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email This email address is being protected from spambots. You need JavaScript enabled to view it..

April 22, 2020

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761115s000lbl.pdf.

On April 22, 2020, the Food and Drug Administration granted accelerated approval to sacituzumab govitecan-hziy (TRODELVY, Immunomedics, Inc.) for adult patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease.

Efficacy was demonstrated in IMMU-132-01 (NCT 01631552), a multicenter, single-arm, trial enrolling 108 patients with metastatic triple negative breast cancer (mTNBC) who received at least two prior treatments for metastatic disease. Patients received sacituzumab govitecan-hziy 10 mg/kg intravenously on days 1 and 8 every 21days. Tumor imaging was obtained every 8 weeks, and patients were treated until disease progression or intolerance to therapy.

The primary efficacy outcome measures were investigator assessed overall response rate (ORR) using RECIST 1.1 and response duration. The ORR was 33.3% (95% CI: 24.6, 43.1). The median response duration was 7.7 months (95% CI: 4.9, 10.8).

The most common adverse reactions (≥25% of patients) were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain. Sacituzumab govitecan-hziy can also cause severe neutropenia and diarrhea.

The recommended sacituzumab govitecan-hziy dose is 10 mg/kg administered by intravenous infusion administered on days 1 and 8 every 21 days until disease progression or unacceptable toxicity.

View full prescribing information for TRODELVY.

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

FDA granted sacituzumab govitecan-hziy orphan drug, fast track, and breakthrough therapy designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email This email address is being protected from spambots. You need JavaScript enabled to view it..

For information on the COVID-19 pandemic, see the following resources:

• FDA: Coronavirus Disease 2019 (COVID-19)
• NCI: Coronavirus: What People With Cancer Should Know
• CDC: Coronavirus (COVID-19)

Follow the Oncology Center of Excellence on Twitter @FDAOncology

Pharmacist’s Applications to Practice

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

Author: Hiba Ahmad, PharmD, BCOP
Clinical Oncology Pharmacist II
Yale-New Haven Hospital Smilow Cancer Center
New Haven, CT

What is the potential role for sacituzumab govitecan-hziy in the treatment of breast cancer?

• Sacituzumab govitecan-hziy is a new treatment option for patients with metastatic triple-negative breast cancer (mTNBC) who have received two or more prior therapies in the metastatic setting.¹  This indication was granted accelerated FDA-approval based on overall response rates and duration of response.²
• Sacituzumab govitecan-hziy is a novel antibody drug conjugate (ADC) comprised of Trop 2, a humanized anti-trophoblast cell-surface antigen 2 monoclonal antibody (hRS7 IgG1k) and connected via cleavable linker (CL2A) to SN-38, a topoisomerase 1 inhibitor conjugate and active metabolite of irinotecan. Trop-2 is overexpressed in several epithelial cell cancer types including TNBC cancer cells, and is linked to tumor cell proliferation. Once sacituzumab govitecan-hziy latches to Trop-2, hRS7 is internalized and exerts cytotoxic effects by the subsequent release of SN-38 in both intra- and extracellular tumor environments, leading to tumor cell DNA damage and apoptosis.^1-4
• TNBC, tumors lacking in human epidermal growth factor receptor 2 (HER2) and estrogen/progesterone receptors, represents approximately 15% of invasive breast cancer diagnoses and is an aggressive tumor subtype with historically limited treatment options. It is more often found in younger females and black women, commonly associated with visceral metastases, and poorer overall prognosis.^4-7 In the past two decades, overall survival (OS) data in this patient population has not improved.^4,5
• While immunotherapy has recently emerged as an NCCN-preferred treatment option in PD-L1 positive TNBC, for those patients who do not express this biomarker, sequential single-agent chemotherapy remains the mainstay of treatment with response rates between 10-15% and progression-free survival (PFS) of 2-3 months. Preferred chemotherapy regimens include doxorubicin, liposomal doxorubicin, paclitaxel, capecitabine, gemcitabine, vinorelbine, and eribulin.^4-8
• Accelerated approval of sacituzumab govitecan-hziy was based on the IMMU-132-01 study, a phase 1/2 single-arm open-label multicenter basket design trial involving 108 heavily pretreated patients with relapsed/refractory mTNBC. Patients were treated with sacituzumab govitecan-hziy 10 mg/kg intravenous infusion on days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity with a median treatment duration of 5.1 months.^2,4
  • Efficacy^1,4 
    • Investigator assessed overall response rate (ORR) was 33.3% (95% CI 24.6-43.1) with 2.8% complete response (CR).
    • Median duration of response (DoR) was 7.7 months (95% CI 4.9-10.8) with 55.6% of patients with a DoR ≥ 6 months and 16.7% of patients with a DoR ≥ 12 months.
    • Median PFS was 5.5 months (95% CI 4.1-6.3).
    • Median OS was 13 months (95% CI 11.2-13.7).
    • Clinical benefit rate was reported at 45.4%.
  • Safety data
    • Out of the 108 patients enrolled in the study, an average of 18.7 doses or 9.6 cycles of sacituzumab govitecan-hziy were administered. Pre-infusion medications were administered in 92% of the patients which included, acetaminophen, antihistamines, H₂ antagonists, glucocorticoids, antiemetics, anxiolytics, and atropine.^1,4
    • The most common (≥ 10%) all grade adverse events (AEs) included nausea, diarrhea, vomiting, constipation, abdominal pain, fatigue, neutropenia, anemia, decreased appetite, alopecia, rash, and respiratory infection.
    • The most common (≥ 10%) grade 3 or higher AEs included anemia (12%) and neutropenia (43%).
    • Febrile neutropenia (FN) of all grades occurred in 9% of the patient population. Grade 3 FN occurred in 6% and grade 4 FN occurred in 2% of patients.^1,4
    • All grade diarrhea occurred in 62% of patients, including 14% grade 2 and 8% grade 3.^1,4
    • Growth factors or blood transfusions were permitted per investigator discretion during treatment, but not prior to initiation of the first dose.¹
    • Treatment interruptions due to adverse events occurred in 44% of the population, with the most common reason being neutropenia.
    • Overall, the IMMU-132-01 study reported diarrhea and neutropenia as the adverse events of greatest concern, leading to black box warnings.^1,4
  • Sacituzumab govitecan-hziy is currently listed as a National Comprehensive Cancer Network (NCCN) “other recommended regimen” as a systemic therapy option for recurrent or stage IV (M1) invasive breast cancer.⁸

What role can the pharmacist play in the management of patients on sacituzumab govitecan-hziy?

• Ensure accurate dosing schedule of 10 mg/kg intravenous (IV) on days 1 and 8 of a 21 day cycle; and adequate pre-medications are given including an antipyretic, H1 and H2 blocker for  the prevention of infusion-related reactions, and a 2-3 drug anti-emetic combination regimen as  Sacituzumab govitecan-hziy is associated with moderate emetic potential.^1,4
• Monitor hematologic and non-hematologic toxicities for appropriate dose reductions^1,4
  • Due to risk of severe or life-threatening neutropenia, dose-adjustments and interruptions are recommended based on ANC on day 1 and day 8 of any cycle, and neutropenic fever
  • Severe non-hematologic toxicity needing dose modifications or interruptions include grade 4 non-hematologic toxicity of any period, or any grade 3/4 nausea, vomiting or diarrhea caused by treatment which remains uncontrolled after administration of antiemetic and anti-diarrheal medications, or other grade 3/4 non-hematologic toxicities lasting >48 hours despite best medical management strategies, or grade 3/4 non-neutropenic hematologic or non-hematologic toxicity delaying dose by 2-3 weeks for recovery to ≤ grade 1 at time of scheduled treatment
• Check for drug interactions as sacituzumab govitecan-hziy is a uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) substrate. UGT1A1 inducers and inhibitors may decrease and increase the sacituzumab govitecan-hziy active metabolite serum concentrations (i.e. SN-38), respectively.^1,4
• Ensure proper preparation and communicate expiration of compounded product with nursing staff
  • Reconstitution¹
    • Only 0.9% normal saline should be used for purposes of reconstitution and dilution.
    • Warm the required vials to room temperature. Reconstitute each 180 mg vial of drug with 20 mL of 0.9% normal saline injection to result in a concentration of 10 mg/mL. Swirl vials gently up to 15 minutes until completely dissolved. The vials should be clear and yellow and void of particulates. Use immediately to prepare diluted infusion solution.
  • Dilution¹
    • The volume of the infusion bag may be adjusted with 0.9% normal saline to achieve a concentration between 1.1 mg/mL-3.4 mg/mL, not to exceed a total volume of 500mL. Total doses should be divided equally between two 500 mL infusion bags and infused sequentially for patients more than 170 kg in weight.
  • Stability¹
    • If the infusion bag is not used immediately, it can be refrigerated for up to 4 hours between 2°C to 8°C (36°F to 46°F). The infusion bag should be administered within 4 hours (including infusion time), after refrigeration.
    • Do not freeze. Protect from light.
• Assist with financial aid applications. Immunomedics provides a patient assistance program. Eligible patients who are uninsured or underinsured may be eligible to receive sacituzumab govitecan-hziy at no cost. The form can be found here: https://www.trodelvy.com/pdf/PAP_Enrollment.pdf⁹

Clinical Pearls

• Sacituzumab govitecan-hziy is a cytotoxic drug and should be administered intravenously. Do not administer as IV push or bolus. Do not mix sacituzumab govitecan-hziy or administer concurrently with other drugs. Once administered, flush the IV line with 20 mL 0.9% normal saline. ¹
• The first infusion should be administered over 3 hours. Patients should be monitored for signs/symptoms of infusion-related reactions during the infusion and at least 30 minutes after the first dose. Subsequent infusions may be administered over 1-2 hours if previous infusion was tolerated without issue. Patients should be monitored for signs/symptoms of infusion-related reactions for at least 30 minutes after infusion. ¹
• Sacituzumab govitecan-hziy has two black box warnings of neutropenia and diarrhea. Close monitoring of hematologic laboratory parameters, electrolytes, and toxicities throughout treatment is needed. ^1,4
• Patients who are homozygous for the UGT1A1*28 allele (reduced UGT1A1 activity) are at higher risk for neutropenia and may be at higher risk for other adverse reactions. The most common adverse reactions and/or severe toxicity concerns related to sacituzumab govitecan-hziy are neutropenia, diarrhea, nausea/vomiting, and hypersensitivity reactions.^1,4
• For prevention of infusion-related reactions, patients should be pre-medicated with antipyretics, H1 and H2 blockers, and dexamethasone before the infusion. If an infusion-related reaction occurs, the infusion rate can be slowed down or interrupted. Severe infusion reactions require permanent discontinuation of sacituzumab govitecan-hziy.^1.4

References

1. Trodelvy (sacituzumab govitecan-hziy) [package insert]. Morris Plains, NJ: Immunomedics, Inc.; April 2020. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761115s000lbl.pdf
2. U.S. Food and Drug Administration. FDA grants accelerated approval to sacituzumab govitecan-hziy for metastatic triple negative breast cancer. Silver Spring, MD: US Food and Drug Administration; Updated 2020 April 22; Accessed 2020 August 8. Available at https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-sacituzumab-govitecan-hziy-metastatic-triple-negative-breast-cancer
3. Sacituzumab Govitecan (IMMU-132): Background & Clinical Trials. Immunomedics. Morris Plains, NJ: Immunomedics, Inc. Accessed 2020 August 8. Available at https://www.immunomedics.com/sacituzumab-govitecan-immu-132/
4. Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med. 2019;380(8):741-751.
5. Plasilova ML, Hayse B, Killelea BK, et al. Features of triple-negative breast cancer: Analysis of 38,813 cases from the National Cancer Database. Medicine (Baltimore). 2016;95(35):e4614.
6. Kohler BA, Sherman RL, Howlader N, et al. Annual report to the nation on the status of cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J Natl Cancer Inst. 2015;107(6):djv048.
7. Cardoso F, Costa A, Senkus E, et al. 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3). Breast 2017;31:244-59.
8. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version 6.2020. Accessed 11 October 2020. Available at https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
9. Immunomedics patient assistance program. Immunomedics, Inc. Available at https://www.trodelvy.com/pdf/PAP_Enrollment.pdf