Sacituzumab Govitecan + Talazoparib for Breast Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Massachusetts General Hospital
Must not be taking: CYP3A inhibitors, P-gp inhibitors
Disqualifiers: CNS metastasis, Heart disease, HIV, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
This research is studying the effect of Antibody-Drug Conjugate Sacituzumab Govitecan in Combination with the Poly (Adenosine Diphosphate \[ADP\]-Ribose) Polymerase (PARP) Inhibitor Talazoparib in Patients with Metastatic Triple-Negative Breast Cancer.
Will I have to stop taking my current medications?
The trial requires that you stop using strong CYP3A inhibitors/inducers or P-gp inhibitors at least 7 days before starting the study. If you are on these medications, you may need to discuss alternatives with your doctor.
What data supports the effectiveness of the drug Sacituzumab Govitecan for breast cancer?
Sacituzumab Govitecan has shown effectiveness in treating metastatic triple-negative breast cancer, with studies indicating it improves progression-free survival and overall survival compared to other treatments. It has been approved for use after patients have tried at least two other therapies, demonstrating a significant response rate and duration of response in clinical trials.12345
What is known about the safety of Sacituzumab Govitecan and Talazoparib for breast cancer?
How is the drug Sacituzumab Govitecan + Talazoparib different from other breast cancer treatments?
Sacituzumab Govitecan is unique because it is an antibody-drug conjugate that specifically targets a protein called Trop-2 on cancer cells, delivering a chemotherapy agent directly to the tumor, which may result in higher concentrations of the drug at the tumor site compared to standard chemotherapy.14111213
Eligibility Criteria
This trial is for adults with stage IV breast cancer that hasn't spread to the brain, who haven't had recent cancer treatments or surgeries, and are not pregnant. They must have a certain level of health, including stable blood sugar levels and an ECOG performance status of 0-1 (fully active or restricted in physically strenuous activity but ambulatory).Inclusion Criteria
My blood tests show my organs and bone marrow are working well.
My breast cancer has spread to other parts of my body.
I am 18 years old or older.
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Exclusion Criteria
Women of child-bearing potential and fertile men, unless using highly effective methods of contraception throughout the study and after study drug discontinuation
I haven't had cancer treatment recently or I've recovered from its side effects.
Pregnant women
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Sacituzumab Govitecan on days 1 and 8 of a 21-day cycle and Talazoparib daily
21 days per cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Sacituzumab Govitecan (Antibody-Drug Conjugate)
- Talazoparib (PARP Inhibitor)
Trial OverviewThe study tests Sacituzumab Govitecan combined with Talazoparib in patients with metastatic triple-negative breast cancer. It aims to see how well these drugs work together against this aggressive form of cancer.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Sacituzumab Govitecan+TalazoparibExperimental Treatment2 Interventions
* Sacituzumab Govitecan is administered on days 1 and 8 of a 21 day cycle.
* Talazoparib is administered daily
Sacituzumab Govitecan is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Trodelvy for:
- Metastatic triple-negative breast cancer
- Locally advanced or metastatic urothelial cancer (withdrawn)
- Metastatic HR+/HER2- breast cancer
🇪🇺 Approved in European Union as Trodelvy for:
- Metastatic triple-negative breast cancer
🇨🇦 Approved in Canada as Trodelvy for:
- Metastatic triple-negative breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General Hospital Cancer CenterBoston, MA
Boston Medical CenterBoston, MA
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
PfizerIndustry Sponsor
References
Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease.
Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. [2023]Sacituzumab govitecan demonstrated significant progression-free survival benefit over chemotherapy in the phase 3 TROPiCS-02 trial in patients with pretreated, endocrine-resistant hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ and HER2-) metastatic breast cancer with limited treatment options. Here, we report the protocol-specified final analysis of overall survival and endpoints by trophoblast cell-surface antigen 2 (Trop-2) expression and other variables.
FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. [2022]On April 22, 2020, the FDA granted accelerated approval to sacituzumab govitecan-hziy (TRODELVY; Immunomedics, Inc.) for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Approval was based on data from the IMMU-132-01 trial, a single-arm, multicohort, multicenter, phase I/II trial of sacituzumab govitecan. The assessment of efficacy was based on 108 patients with mTNBC who had previously received at least two prior lines of therapy in the metastatic setting and who received sacituzumab govitecan 10 mg/kg i.v. The assessment of safety was based on 408 patients with advanced solid tumors who had received sacituzumab govitecan at doses up to 10 mg/kg i.v. The primary efficacy endpoint was investigator-assessed objective response rate (ORR) and duration of response (DoR) was a key secondary endpoint. The ORR was 33.3% [36/108; 95% confidence interval (CI), 24.6-43.1], and median DoR among responders was 7.7 months (95% CI, 4.9-10.8). The most common adverse reactions occurring in ≥25% of patients were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain. This article summarizes the FDA review process and data supporting the approval of sacituzumab govitecan.
Sacituzumab Govitecan: First Approval. [2021]Sacituzumab govitecan (sacituzumab govitecan-hziy; Trodelvy™) is a Trop-2-directed antibody conjugated to a topoisomerase I inhibitor (SN-38) that is being developed by Immunomedics for the treatment of solid tumours, including breast cancer. In April 2020, sacituzumab govitecan received accelerated approval in the USA for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Sacituzumab govitecan is undergoing phase III development for breast cancer in the USA and EU, and phase II development for urothelial cancer. It is also being explored for brain metastases, glioblastoma, endometrial cancer and prostate cancer. This article summarizes the milestones in the development of sacituzumab govitecan leading to this first approval for mTNBC.
The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer. [2022]Sacituzumab govitecan (SG) is an antineoplastic agent which combines a humanized monoclonal antibody binding to trophoblast cell surface antigen-2 (Trop-2)-expressing cancer cells, linked with cytotoxic moiety SN-38 (govitecan) with topoisomerase I inhibitor action. On 22 November 2021, a marketing authorization valid through the European Union (EU) was issued under the European Medicines Agency (EMA)'s accelerated assessment program for SG as monotherapy for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, including at least one of them for advanced disease. The assessment was based on results from an open-label, randomized, phase III trial to evaluate the safety, tolerability, pharmacokinetics and efficacy of SG versus treatment of physician's choice (TPC) in patients with mTNBC who received at least two prior treatments including at least one of them for advanced disease. The efficacy results in the overall population, based on mature data, showed a statistically significant improvement of SG over TPC in progression-free survival (PFS) and overall survival (OS). The median PFS was 4.8 months versus 1.7 months [hazard ratio (HR) = 0.43, n = 529; 95% CI 0.35-0.54; P 30%) side effects of SG were diarrhea, neutropenia, nausea, fatigue, alopecia, anemia, constipation and vomiting. The aim of this manuscript is to summarize the scientific review of the application leading to regulatory approval in the EU.
Talazoparib: First Global Approval. [2020]Talazoparib (TALZENNA™) is an oral inhibitor of the polyadenosine 5'-diphosphoribose polymerase (PARP) enzymes, which play a critical role in repairing DNA single-strand breaks. It has been developed by Pfizer and was recently approved in the USA for the treatment of adults with deleterious or suspected deleterious germline BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer (as detected by a US FDA-approved assay). A regulatory assessment for talazoparib in this patient population is underway in the EU, with talazoparib also undergoing development for use in metastatic castration-resistant prostate cancer and various solid tumours, and as neoadjuvant therapy in early triple negative breast cancer. This article summarizes the milestones in the development of talazoparib leading to its first approval for the treatment of adults with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative, locally advanced or metastatic breast cancer.
Evidence to date: talazoparib in the treatment of breast cancer. [2020]Approximately 5-10% of all patients diagnosed with breast cancer have germline BRCA1/2 mutations, which make their disease more susceptible to DNA-damaging agents and a new class of drugs known as poly(ADP-ribose) polymerase (PARP) inhibitors. Talazoparib is a new PARP inhibitor that has been recently approved for use in patients with metastatic breast cancer with germline BRCA mutations after a phase III trial showed superior progression-free survival when compared to standard chemotherapy. In this review, we analyze the development of talazoparib as well as its safety profile and the potential role of the combination therapy with standard cytotoxic drugs and with novel therapies.
Talazoparib Bests Chemo for Breast Cancer. [2019]Patients with advanced or metastatic HER2-negative breast cancer and germline BRCA1/2 mutations may benefit from talazoparib, according to data from a phase III trial. Compared with chemotherapy, the investigational PARP inhibitor induced some complete responses, prolonged progression-free survival, and improved patients' overall quality of life.
Talazoparib in Patients with a Germline BRCA-Mutated Advanced Breast Cancer: Detailed Safety Analyses from the Phase III EMBRACA Trial. [2022]In the EMBRACA phase III study (NCT01945775), talazoparib was associated with a significantly prolonged progression-free survival (PFS) compared with physician's choice of chemotherapy (PCT) in germline BRCA1/2-mutated HER2-negative advanced breast cancer (ABC). Herein, the safety profile of talazoparib is explored in detail.
Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant. [2021]Label="PURPOSE">Talazoparib has demonstrated efficacy in patients with BRCA-positive metastatic breast cancer. This study evaluated the pathologic response of talazoparib alone for 6 months in patients with a known germline BRCA pathogenic variant (gBRCA-positive) and operable breast cancer.
An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer. [2023]Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets the human trophoblast cell-surface antigen 2 to deliver SN-38 to cancer cells. In this study, we assessed the efficacy and safety of SG in patients with relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC).
Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. [2019]Standard chemotherapy is associated with low response rates and short progression-free survival among patients with pretreated metastatic triple-negative breast cancer. Sacituzumab govitecan-hziy is an antibody-drug conjugate that combines a humanized monoclonal antibody, which targets the human trophoblast cell-surface antigen 2 (Trop-2), with SN-38, which is conjugated to the antibody by a cleavable linker. Sacituzumab govitecan-hziy enables delivery of high concentrations of SN-38 to tumors.
Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. [2023]Hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer.