sac-TMT + Pembrolizumab for Breast Cancer

Recruiting at 311 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Pembrolizumab

Must not be taking: CYP3A4 inducers/inhibitors, Olaparib

Disqualifiers: BRCA mutation, Cardiovascular disease, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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: 6

Duration: 24 weeks

1530 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs: sacituzumab tirumotecan (an experimental treatment) and pembrolizumab (an immunotherapy drug), for individuals with triple-negative breast cancer (TNBC) who did not fully respond to initial treatment before surgery. The goal is to determine if this combination can prevent cancer recurrence more effectively than the usual treatments selected by doctors. Suitable participants typically have TNBC, have completed surgery, and did not achieve a full response to their pre-surgery treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires a 2-week period without taking strong inducers or inhibitors of CYP3A4 before starting sacituzumab tirumotecan. If you are on such medications, you may need to stop them. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that sacituzumab tirumotecan, when combined with pembrolizumab, is generally safe. Earlier studies with patients who had solid tumors found that most side effects were not serious. Common side effects included mild to moderate fatigue and nausea.

Pembrolizumab has approval for treating various cancers, indicating its well-established safety. Whether used alone or with sacituzumab tirumotecan, it is usually well-tolerated.

In summary, while some side effects can occur, they are typically manageable and not severe. Always consult a healthcare professional to understand what this means for individual circumstances. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sacituzumab tirumotecan combined with pembrolizumab for breast cancer because it offers a unique approach compared to traditional treatments like chemotherapy or hormone therapy. Unlike most treatments, sacituzumab tirumotecan is an antibody-drug conjugate that specifically targets cancer cells, delivering chemotherapy directly to them, which could potentially reduce side effects and enhance effectiveness. Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. This combination could offer a powerful, more targeted option for patients, possibly leading to better outcomes and fewer adverse effects.

What evidence suggests that this trial's treatments could be effective for triple-negative breast cancer?

Research has shown that combining sacituzumab tirumotecan with pembrolizumab, which participants in this trial may receive, can lead to better outcomes for patients with triple-negative breast cancer (TNBC). Studies have found that this combination helps patients live longer without the cancer returning or spreading, compared to other treatments. Specifically, using sacituzumab tirumotecan with pembrolizumab has extended the time patients remain free from invasive cancer in similar high-risk cases. Early results suggest this combination might be more effective than using pembrolizumab alone or with other chemotherapy drugs like capecitabine, another treatment option in this trial. This treatment targets cancer cells more precisely, potentially improving disease control. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for individuals with triple-negative breast cancer (TNBC) who didn't fully respond to neoadjuvant therapy and surgery. Participants must have completed any required radiation, be able to continue on pembrolizumab, and not show signs of cancer relapse. Strict contraception or abstinence is required for both male and female participants during the trial and for a period after.

Inclusion Criteria

I am HBsAg positive but have been on HBV therapy for 4+ weeks with an undetectable viral load.

My surgery did not remove all of my cancer.

I can continue taking pembrolizumab as a follow-up treatment.

Exclusion Criteria

I've had cancer treatment like chemotherapy or immunotherapy after my main treatment, except for radiation.

I have severe nerve damage in my hands or feet.

I had radiation therapy less than 3 weeks ago or need steroids for radiation side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab every 6 weeks in combination with sacituzumab tirumotecan every 2 weeks for 24 weeks, or pembrolizumab with or without capecitabine for 24 weeks

24 weeks

Bi-weekly visits for sacituzumab tirumotecan, every 6 weeks for pembrolizumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to ~77 months

Long-term Follow-up

Participants are monitored for overall survival and distant recurrence-free survival

Up to ~101 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Sacituzumab Tirumotecan

Trial Overview The study compares sacituzumab tirumotecan (sac-TMT) combined with pembrolizumab against the physician's choice of treatment in TNBC patients post-surgery without a pathological complete response. The main goal is to see if sac-TMT plus pembrolizumab improves disease-free survival compared to other treatments.

How Is the Trial Designed?

Group I: Pembrolizumab + sacituzumab tirumotecan Experimental Treatment 2 Interventions

Participants receive pembrolizumab every 6 weeks (q6w) in combination with sacituzumab tirumotecan every 2 weeks (q2w) for 24 weeks. In addition, participants receive an antihistamine, an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to sacituzumab tirumotecan infusions.

Group II: Treatment of Physician's Choice Active Control 2 Interventions

Participants receive pembrolizumab q6w or pembrolizumab q6w in combination with capecitabine (twice daily \[BID\] on Days 1 to 14 and 22 to 35 every 42 days x 4 \[2 weeks 1, 1 week off\]) for 24 weeks.

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

Published Research Related to This Trial

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[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 (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

In a study of 120 patients with advanced melanoma, the combination of pembrolizumab with dabrafenib and trametinib (triplet therapy) significantly improved progression-free survival (PFS) to 16.9 months compared to 10.7 months with the doublet therapy (dabrafenib and trametinib) alone.

While triplet therapy showed better outcomes in PFS and duration of response, it also resulted in a higher incidence of severe treatment-related adverse events (58% vs. 25% in the doublet group), indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-022 part 3: a randomized, double-blind, phase 2 study of pembrolizumab, dabrafenib, and trametinib in BRAF-mutant melanoma. Ferrucci, PF., Di Giacomo, AM., Del Vecchio, M., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06841354

A Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) ... 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 ...

2. onclive.com onclive.com/view/sacituzumab-tirumotecan-plus-pembrolizumab-is-set-to-be-evaluated-in-tnbc

Sacituzumab Tirumotecan Plus Pembrolizumab Is Set to ... T-DXd significantly improved iDFS over T-DM1 in patients with high-risk HER2-positive early breast cancer post neoadjuvant therapy. The safety ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS616

A phase 3, randomized study of adjuvant sacituzumab ... This study (NCT06393374) evaluates adjuvant sac-TMT + pembrolizumab vs treatment of physician's choice (TPC; pembrolizumab ± capecitabine) in participants with ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06966700

A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, ... Live longer without the cancer growing, spreading, or coming back compared to people who receive only pembrolizumab with chemotherapy. Official Title. A Phase 3 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12142944/

Results of a phase 1/2 study of sacituzumab tirumotecan in ... We report results from the phase 1 dose-escalation cohorts in advanced solid tumors and phase 2 expansion cohorts for metastatic triple-negative breast cancer ...

6. msdclinicaltrials.com msdclinicaltrials.com/trial/nct06393374/

Sacituzumab Tirumotecan Plus Pembrolizumab Versus TPC ... This is a randomized, open-label study comparing the efficacy and safety of adjuvant sacituzumab tirumotecan (MK-2870) in combination with pembrolizumab ...