Trodelvy (sacituzumab govitecan-hziy) - 2 indications

Scroll down for more information on each indication:

• for adults with metastatic triple-negative breast cancer; approved April 2020
• for adults with locally advanced or metastatic urothelial cancer; approved April 2021

General Information

Trodelvy (sacituzumab govitecan-hziy) is aTrop-2-directed antibody and topoisomerase inhibitor conjugate.

Trodelvy is specifically indicated for the following:

• the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease;
• the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PDL1) inhibitor.

Trodelvy is supplied as a solution for intravenous administration. The recommended dose of Trodelvy is 10mg/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 10mg/kg.

• 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.
• 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.

Mechanism of Action

Trodelvy (sacituzumab govitecan-hziy) is a Trop-2-directed antibody-drug conjugate. Sacituzumab is a humanized antibody that recognizes Trop-2. The small molecule, SN-38, is a topoisomerase I inhibitor, which is covalently attached to the antibody by a linker.  Pharmacology data suggest that sacituzumab govitecan-hziy binds to Trop-2-expressing cancer cells and is internalized with the subsequent release of SN-38 via hydrolysis of the linker. SN-38 interacts with topoisomerase I and prevents re-ligation of topoisomerase I-induced single strand breaks. The resulting DNA damage leads toapoptosis and cell death. Sacituzumab govitecan-hziy decreased tumor growth in mouse xenograft models of triple-negative breast cancer.

Side Effects

Adverse effects associated with the use of Trodelvy may include, but are not limited to, the following:

•  nausea
• neutropenia
• diarrhea
• fatigue
• anemia
• vomiting
• alopecia
• constipation
• rash
• decreased appetite
• abdominal pain

The Trodelvy drug label comes with the following Black Box Warning: 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.

Indication 1 - for adults with metastatic triple-negative breast cancer

approved April 2020

Clinical Trial Results

Trodelvy was 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.

The FDA approval of Trodelvy was based on study IMMU-132-01, a multicenter, single-arm, trial that enrolled 108 patients with metastatic triple-negative breast cancer (mTNBC) who had received at least two prior treatments for metastatic disease. 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. Trodelvy demonstrated an ORR of 33.3% and a median DoR of 7.7 months, as determined by local assessment.

Indication 2 - for adults with locally advanced or metastatic urothelial cancer

approved April 2021

Clinical Trial Results

Trodelvy was approved under accelerated approval based on tumor response rate and duration of response. Continued approval is contingent upon verification and description of clinical benefit in a confirmatory trial.

FDA accelerated approval was based on data from the international Phase 2, single-arm TROPHY study. The international, multi-center, open-label, multi-cohort, single-arm study evaluated Trodelvy monotherapy or combination therapy in patients with metastatic UC after progression on a platinum-based regimen and anti-PD-1/PD-L1-based immunotherapy. In Cohorts 1 and 2, patients received Trodelvy 10 mg/kg administered intravenously on Days 1 and 8 of a 21-day cycle to be continued until disease progression or loss of clinical benefit. Accelerated approval was based on the objective response rate (ORR) and duration of response (DoR) established in Cohort 1.Of the 112 patients who were evaluable for efficacy, 27.7% of those treated with Trodelvy responded to treatment, with 5.4% experiencing a complete response and 22.3% experiencing a partial response. The median duration of response was 7.2 months.