Sacituzumab Tirumotecan + Pembrolizumab for Breast Cancer

Recruiting at 12 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: CNS metastases, Cardiovascular disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to ~61 months

1000 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must not have received prior systemic treatment for the specific type of breast cancer being studied.

What data supports the effectiveness of the drug combination of Sacituzumab Tirumotecan and Pembrolizumab for breast cancer?

Pembrolizumab, when combined with chemotherapy, has shown to improve progression-free survival in patients with advanced triple-negative breast cancer whose tumors express PD-L1. Additionally, pembrolizumab has been effective in treating other cancers like melanoma and lung cancer, suggesting its potential benefit in breast cancer treatment. ^{1 2 3 4 5}

What is known about the safety of Sacituzumab Govitecan and Pembrolizumab in humans?

Sacituzumab Govitecan has been associated with adverse events like neutropenia (low white blood cell count), diarrhea, colitis (inflammation of the colon), and sepsis (a severe infection), with most occurring within 30 days of treatment. Pembrolizumab is generally well tolerated, but there is a small risk of fatal adverse events, particularly when combined with chemotherapy, with common issues being infections, heart problems, and lung inflammation. ^{6 7 8 9 10}

How is the drug Sacituzumab Tirumotecan + Pembrolizumab unique for breast cancer treatment?

This drug combination is unique because it combines pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with sacituzumab tirumotecan, which is designed to deliver chemotherapy directly to cancer cells. This approach aims to enhance the immune response while directly targeting cancer cells, potentially offering a new option for patients with limited treatment choices. ^{1 11 12 13 14}

What is the purpose of this trial?

Researchers want to know if sacituzumab tirumotecan given alone or with pembrolizumab can treat triple negative breast cancer (TNBC). The main goal of this study is to learn if people treated with sacituzumab tirumotecan alone or with pembrolizumab live longer overall or without the cancer growing or spreading compared to people treated with chemotherapy.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with triple-negative breast cancer that's locally advanced and can't be removed by surgery or has spread, who haven't had systemic treatment for this stage. They should have finished any previous early-stage cancer treatments at least 6 months prior and must be able to receive one of the standard chemotherapies offered.

Inclusion Criteria

My triple-negative breast cancer cannot be surgically removed and is advanced.

I haven't had systemic treatment for my advanced triple-negative breast cancer.

I finished my early-stage breast cancer treatment at least 6 months ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab tirumotecan alone or in combination with pembrolizumab, or treatment of physician's choice until disease progression, toxicity, or discontinuation

Up to ~61 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to ~61 months

Treatment Details

Interventions

• Pembrolizumab
• Sacituzumab tirumotecan

Trial Overview The study tests Sacituzumab Tirumotecan alone or combined with Pembrolizumab against standard chemotherapy options. The goal is to see if these new treatments help patients live longer without their cancer growing compared to those receiving only chemotherapy.

Participant Groups

Group I: Arm B: Sacituzumab Tirumotecan + Pembrolizumab Experimental Treatment 3 Interventions

Participants receive sacituzumab tirumotecan IV 4 mg/kg Q2W until disease progression, toxicity or discontinuation PLUS pembrolizumab IV 400 mg every 6 weeks (Q6W) for up to 18 administrations (up to \~2 years). Additionally, participants may receive rescue medication per approved product label, at the discretion of the investigator.

Group II: Arm A: Sacituzumab Tirumotecan Experimental Treatment 2 Interventions

Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) until disease progression, toxicity or discontinuation. Additionally, participants may receive rescue medication per approved product label, at the discretion of the investigator.

Group III: Arm C: Treatment of Physician's Choice (TPC) Active Control 4 Interventions

Participants receive physician's choice of chemotherapy agent(s): paclitaxel IV 80 mg/m\^2 once every week (Q1W) OR paclitaxel IV 90 mg/m\^2 on Days 1, 8, and 15, every 4 weeks (Q4W) OR nab-paclitaxel IV 100 mg/m\^2 on Days 1, 8, and 15, Q4W OR gemcitabine IV 1000 mg/m\^2 on Days 1 and 8, every 3 weeks (Q3W) PLUS carboplatin IV area under the curve (AUC) 2 mg/mL/min on Days 1 and 8, Q3W, until disease progression, toxicity or discontinuation.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Pembrolizumab is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. du Rusquec, P., de Calbiac, O., Robert, M., et al.[2023]

In a phase 2 study involving 216 patients with stage III non-small cell lung cancer (NSCLC), the combination of pembrolizumab and concurrent chemoradiation therapy (cCRT) showed a high objective response rate of approximately 70.5% in cohort A and 70.6% in cohort B, indicating strong antitumor activity.

The treatment was associated with manageable safety, with grade 3 or higher pneumonitis occurring in 8.0% of cohort A and 6.9% of cohort B, suggesting that while there are risks, the benefits of this treatment approach may outweigh them for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. Jabbour, SK., Lee, KH., Frost, N., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, was found to be well tolerated and more effective than placebo in treating early-stage triple-negative breast cancer (TNBC), regardless of PD-L1 status, based on a systematic review of 15 clinical trials.

In advanced-stage TNBC, pembrolizumab demonstrated similar efficacy to single-agent chemotherapy but with a better safety profile, and when combined with chemotherapy, it significantly improved median progression-free survival compared to chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab based therapies in triple-negative breast cancer: A systematic review of clinical trials. Ali, MA., Aiman, W., Shah, SS., et al.[2022]

In a meta-analysis of 11 clinical trials involving 3713 patients, the overall incidence of fatal adverse events (FAEs) associated with pembrolizumab was found to be 1.2%, indicating a relatively low risk of severe complications from this immune checkpoint inhibitor.

The incidence of FAEs varied significantly by tumor type, with breast cancer patients experiencing a higher risk (3.1%) compared to melanoma patients (0.2%), and the combination of pembrolizumab with chemotherapy resulted in a much higher incidence of FAEs (7.0%) compared to pembrolizumab alone (0.7%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal Adverse Events Associated with Pembrolizumab in Cancer Patients: A Meta-Analysis. Sher, AF., Golshani, GM., Wu, S.[2020]

In a phase 3 trial involving 622 patients with metastatic triple-negative breast cancer, pembrolizumab did not significantly improve overall survival compared to standard chemotherapy, with median survival times of 9.9 months for pembrolizumab and 10.8 months for chemotherapy.

Pembrolizumab showed a manageable safety profile, with fewer severe treatment-related adverse events compared to chemotherapy, suggesting it may be safer for some patients despite not demonstrating superior efficacy overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Winer, EP., Lipatov, O., Im, SA., et al.[2021]

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]

A total of 1,884 adverse event reports related to sacituzumab govitecan were analyzed, identifying 114 adverse event signals, with most occurring within 30 days of treatment initiation, highlighting the importance of monitoring for early reactions.

Risk factors for hospitalization due to adverse events included being male and experiencing conditions like colitis, febrile neutropenia, and sepsis, indicating specific patient profiles that may require closer observation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). Li, X., Zhang, L., Hu, S., et al.[2023]

In the KEYNOTE-355 trial, the combination of pembrolizumab and chemotherapy significantly improved progression-free and overall survival in patients with advanced triple-negative breast cancer with a PD-L1 combined positive score of at least 10.

Patient-reported outcomes showed no significant differences in quality of life or functioning between the pembrolizumab and placebo groups at week 15, indicating that while pembrolizumab is effective, it does not negatively impact patients' quality of life compared to standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life With Pembrolizumab+Chemotherapy Versus Placebo+Chemotherapy for Advanced Triple-Negative Breast Cancer: KEYNOTE-355. Cescon, DW., Schmid, P., Rugo, HS., et al.[2023]

In a phase Ib study involving 64 patients with Stage IV non-small cell lung cancer (NSCLC), the combination of necitumumab and pembrolizumab showed a confirmed overall response rate of 23.4%, indicating modest efficacy in this patient population.

The treatment was well-tolerated, with no dose-limiting toxicities reported, and the safety profile was consistent with typical effects of epidermal growth factor receptor inhibitors and immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of necitumumab and pembrolizumab combination therapy in patients with Stage IV non-small cell lung cancer. Besse, B., Garrido, P., Cortot, AB., et al.[2021]

In the KEYNOTE-355 trial, patients with previously untreated metastatic triple-negative breast cancer (mTNBC) who received pembrolizumab combined with chemotherapy experienced a significant improvement in quality-adjusted survival, gaining an average of 3.7 months more time without symptoms or treatment toxicity compared to those receiving chemotherapy alone.

The benefits of pembrolizumab plus chemotherapy increased over time, with a 20% relative gain in quality-adjusted survival at a maximum follow-up of 52 months, indicating both efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. Huang, M., O'Shaughnessy, J., Haiderali, A., et al.[2023]

Pembrolizumab (P) can be safely combined with various chemotherapy agents, including gemcitabine and liposomal doxorubicin, in patients with advanced solid tumors, as shown in a phase Ib trial involving 49 patients.

The combination treatment resulted in eight partial responses across different tumor types, indicating potential efficacy, but further studies are needed to confirm if the response duration is better than chemotherapy or immunotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). Weiss, GJ., Waypa, J., Blaydorn, L., et al.[2022]

References

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

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. [2023]

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

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. [2022]

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

Pemetrexed and Platinum Plus Pembrolizumab in Patients With Metastatic Nonsquamous NSCLC by Tumor Burden at Baseline: A Post Hoc Efficacy Analysis of KEYNOTE-189. [2022]

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

Remarkable response with pembrolizumab plus albumin-bound paclitaxel in 2 cases of HER2-positive metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy. [2020]

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

Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab based therapies in triple-negative breast cancer: A systematic review of clinical trials. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Fatal Adverse Events Associated with Pembrolizumab in Cancer Patients: A Meta-Analysis. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. [2021]

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

Sacituzumab Govitecan: First Approval. [2021]

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

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). [2023]

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

Health-Related Quality of Life With Pembrolizumab+Chemotherapy Versus Placebo+Chemotherapy for Advanced Triple-Negative Breast Cancer: KEYNOTE-355. [2023]

12. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of necitumumab and pembrolizumab combination therapy in patients with Stage IV non-small cell lung cancer. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. [2023]

14. England pubmed.ncbi.nlm.nih.gov

A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). [2022]