Sacituzumab Govitecan + Talazoparib for Breast Cancer

Recruiting at 1 trial location

Overseen By Aditya Bardia, MD, MPH

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Massachusetts General Hospital

Must not be taking: CYP3A inhibitors, P-gp inhibitors

Disqualifiers: CNS metastasis, Heart disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days per cycle

75 Participants Needed

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. ^{1 2 3 4 5}

What is known about the safety of Sacituzumab Govitecan and Talazoparib for breast cancer?

Talazoparib has been studied in patients with advanced breast cancer and has shown a safety profile that is generally manageable, with side effects similar to those seen with chemotherapy. Common side effects include low blood cell counts, fatigue, and nausea. ^{6 7 8 9 10}

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. ^{1 4 11 12 13}

Research Team

Laura M Spring, M.D.

Principal Investigator

Massachusetts General Hospital

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.

Your blood sugar levels when fasting and your average blood sugar over the past few months are within specific ranges.

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

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
• Talazoparib

Trial Overview The 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

Group I: Sacituzumab Govitecan+Talazoparib Experimental Treatment 2 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

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

In a phase 3 trial involving 543 patients with pretreated, endocrine-resistant HR+ and HER2- metastatic breast cancer, sacituzumab govitecan significantly improved overall survival compared to chemotherapy, with a median survival of 14.4 months versus 11.2 months.

Sacituzumab govitecan also showed a higher objective response rate (21% vs 14%) and better quality of life outcomes, indicating it is a promising new treatment option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Rugo, HS., Bardia, A., Marmé, F., et al.[2023]

Sacituzumab govitecan-hziy (TRODELVY) received accelerated FDA approval for treating metastatic triple-negative breast cancer (mTNBC) based on a trial involving 108 patients, showing an objective response rate of 33.3% and a median duration of response of 7.7 months.

The safety profile was assessed in a larger group of 408 patients, with common side effects including nausea, neutropenia, and fatigue, occurring in 25% or more of patients, indicating that while effective, the treatment can have significant adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. Wahby, S., Fashoyin-Aje, L., Osgood, CL., et al.[2022]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and delivers a topoisomerase I inhibitor, showing promise in treating metastatic triple-negative breast cancer (mTNBC) after at least two prior therapies.

In April 2020, it received accelerated approval in the USA for mTNBC, and it is currently undergoing further clinical trials for various cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. Syed, YY.[2021]

Sacituzumab govitecan (SG) has been approved in the EU for treating adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have undergone at least two prior systemic therapies, showing significant improvements in progression-free survival (4.8 months vs. 1.7 months) and overall survival (11.8 months vs. 6.9 months) compared to treatment of physician's choice.

The most common side effects of SG include diarrhea, neutropenia, nausea, fatigue, alopecia, anemia, constipation, and vomiting, occurring in more than 30% of patients, indicating that while SG is effective, it also has notable adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer. Michaleas, S., Moreno Oliver, A., Mueller-Berghaus, J., et al.[2022]

Talazoparib is an oral PARP inhibitor recently approved in the USA for treating adults with specific types of breast cancer, particularly those with BRCA mutations, highlighting its targeted efficacy in a defined patient population.

The drug is also being explored for use in other cancers, including metastatic castration-resistant prostate cancer and early triple negative breast cancer, indicating its potential versatility in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib: First Global Approval. Hoy, SM.[2020]

Talazoparib, a PARP inhibitor, has been approved for treating metastatic breast cancer in patients with germline BRCA1/2 mutations, showing superior progression-free survival compared to standard chemotherapy in a phase III trial.

The review discusses talazoparib's safety profile and explores its potential effectiveness when combined with standard cytotoxic drugs and novel therapies, highlighting its role in enhancing treatment options for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence to date: talazoparib in the treatment of breast cancer. Exman, P., Barroso-Sousa, R., Tolaney, SM.[2020]

In a phase III trial, talazoparib, a PARP inhibitor, showed promising results for patients with advanced or metastatic HER2-negative breast cancer and BRCA1/2 mutations, leading to some complete responses and prolonged progression-free survival.

Patients treated with talazoparib also experienced improved overall quality of life compared to those receiving chemotherapy, highlighting its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib Bests Chemo for Breast Cancer. [2019]

In the EMBRACA phase III study involving 412 patients, talazoparib significantly improved progression-free survival compared to physician's choice of chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer.

Talazoparib was generally well tolerated, with manageable hematologic toxicities that rarely led to permanent discontinuation (<2% of patients), and it resulted in better patient-reported outcomes and lower healthcare resource utilization compared to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib in Patients with a Germline BRCA-Mutated Advanced Breast Cancer: Detailed Safety Analyses from the Phase III EMBRACA Trial. Hurvitz, SA., Gonçalves, A., Rugo, HS., et al.[2022]

In a study of 20 patients with operable BRCA-positive breast cancer, talazoparib treatment for 6 months resulted in a 53% rate of complete pathologic response (RCB-0) and a 63% rate of minimal residual disease (RCB-0/I), indicating significant efficacy without chemotherapy.

While talazoparib was effective, it also caused manageable side effects, with 40% of patients experiencing grade 3 anemia and requiring transfusions, highlighting the importance of monitoring and managing toxicity during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant. Litton, JK., Scoggins, ME., Hess, KR., et al.[2021]

Sacituzumab govitecan (SG) demonstrated effectiveness in treating relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC), with a median overall survival of 12.9 months and an objective response rate of 34% based on an analysis of 412 patients across three trials.

The treatment was associated with significant adverse effects, particularly myelosuppression, with 46% of patients experiencing grade ≥3 neutropenia, and there were four treatment-related deaths reported, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer. Cheng, SX., Chen, QC., Lin, GH., et al.[2023]

In a phase 1/2 trial involving 108 patients with heavily pretreated metastatic triple-negative breast cancer, sacituzumab govitecan-hziy demonstrated a response rate of 33.3%, with a median duration of response of 7.7 months, indicating its efficacy in this challenging patient population.

The treatment was associated with significant myelotoxic effects, including anemia and neutropenia, but overall survival was promising at a median of 13.0 months, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. Bardia, A., Mayer, IA., Vahdat, LT., et al.[2019]

Sacituzumab govitecan (SG) significantly improved progression-free survival (PFS) in patients with endocrine-resistant HR+/HER2- metastatic breast cancer, showing a 34% reduction in the risk of progression or death compared to standard chemotherapy.

The safety profile of SG was manageable, with notable grade ≥ 3 adverse events including neutropenia and diarrhea, but it still represents a promising treatment option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. Rugo, HS., Bardia, A., Marmé, F., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

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]

3. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. [2021]

5. England pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Talazoparib: First Global Approval. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Evidence to date: talazoparib in the treatment of breast cancer. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Talazoparib Bests Chemo for Breast Cancer. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Talazoparib in Patients with a Germline BRCA-Mutated Advanced Breast Cancer: Detailed Safety Analyses from the Phase III EMBRACA Trial. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. [2023]