Sacituzumab Tirumotecan + Pembrolizumab for Breast Cancer

Recruiting at 319 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Steroids

Disqualifiers: Curative cancer, Autoimmune 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: 2

Duration: Up to ~38 months

1200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether the drug sacituzumab tirumotecan, administered alone or with pembrolizumab (an immunotherapy drug), is more effective than standard treatments selected by doctors for certain types of advanced breast cancer. It focuses on patients with hormone receptor-positive (HR+) and HER2-negative breast cancer that cannot be surgically removed or has metastasized. The trial seeks participants whose cancer has worsened despite previous hormone treatments and who are eligible for chemotherapy. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants must have adequate organ function and that those with HIV or Hepatitis B/C must have controlled viral loads, which might imply some medication management.

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

Research has shown that sacituzumab tirumotecan is generally safe and well-tolerated by patients with advanced solid tumors. Common side effects, such as tiredness and nausea, are manageable.

Pembrolizumab has undergone extensive study and received FDA approval for treating other cancers. It has a good safety record, with common side effects including tiredness, nausea, and mild itching.

These treatments aim to help breast cancer patients. While side effects can occur, research suggests that both drugs are safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sacituzumab Tirumotecan and its combination with Pembrolizumab for breast cancer because they offer a fresh approach to treatment. Sacituzumab Tirumotecan is a next-generation antibody-drug conjugate that targets the Trop-2 protein, which is often found at high levels on breast cancer cells. This allows it to deliver chemotherapy directly to the cancer cells, potentially reducing damage to healthy cells. Meanwhile, Pembrolizumab is an immune checkpoint inhibitor that helps the immune system better recognize and attack cancer cells. This combination could enhance the effectiveness of treatment by both directly targeting cancer cells and boosting the body's immune response, offering hope for better outcomes compared to standard chemotherapy options like paclitaxel or capecitabine.

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

In this trial, participants will receive different treatments to evaluate their effectiveness in treating HR+/HER2- breast cancer. Research has shown that sacituzumab tirumotecan, administered to participants in Arm A, may slow the disease more effectively than standard chemotherapy. In Arm B, participants will receive a combination of sacituzumab tirumotecan and pembrolizumab. Early signs suggest this combination might offer additional benefits, as pembrolizumab enhances the immune system's ability to fight cancer cells. Together, these treatments might control the cancer longer than current options. Arm C involves treatment of the physician's choice, using standard chemotherapy options. ^{6 7 8 9 10}

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 adults with HR+/HER2- advanced or metastatic breast cancer that's worsened after hormone therapy, including one with a CDK4/6 inhibitor. They should be able to undergo chemotherapy, have good physical function (ECOG 0-1), and controlled HIV if positive. Hepatitis B patients can join if treated for 4 weeks and virus undetectable; same for Hepatitis C with no detectable virus.

Inclusion Criteria

My breast cancer cannot be surgically removed, is HR+ and HER2-.

I had Hepatitis C but my viral load is now undetectable.

My organs are functioning well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab tirumotecan as a single agent or in combination with pembrolizumab, or Treatment of Physician's Choice (TPC) until progressive disease or discontinuation

Up to ~38 months

Every 2 weeks for sacituzumab tirumotecan, every 6 weeks for pembrolizumab, variable for TPC

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to ~77 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Sacituzumab Tirumotecan

Trial Overview

The study tests Sacituzumab Tirumotecan alone and combined with Pembrolizumab against doctors' choice of treatment in participants. It aims to see which option better stops the cancer from progressing using standard criteria assessed by independent reviewers who don't know which treatment was given.

How Is the Trial Designed?

Group I: Arm B:Pembrolizumab + Sacituzumab tirumotecan Experimental Treatment 2 Interventions

Participants receive 4 mg/kg of sacituzumab tirumotecan Q2W via IV infusion until progressive disease or discontinuation PLUS 400 mg of pembrolizumab once every 6 weeks (Q6W) via IV infusion for up to 18 administrations (up to \~2 years).

Group II: Arm A: Sacituzumab tirumotecan Experimental Treatment 1 Intervention

Participants receive 4 mg/kg of sacituzumab tirumotecan once every 2 weeks (Q2W) via intravenous (IV) infusion until progressive disease or discontinuation.

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

At the physician's discretion, participants receive chemotherapy of 80 mg/m\^2 of paclitaxel once every week (Q1W) via IV infusion OR 90 mg/m\^2 of paclitaxel once every 4 weeks (Q4W) via IV infusion OR 100 mg/m\^2 of nab-paclitaxel Q4W via IV infusion OR 1000 mg/m\^2 of capecitabine every 3 weeks (Q3W) orally OR 50 mg/m\^2 of liposomal doxorubicin once every 4 weeks (Q4W) via IV infusion, until progressive disease or discontinuation.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

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

Sacituzumab govitecan (SG) showed promising efficacy in treating advanced epithelial cancers, with partial response rates of 22.2% in endometrial cancer and 17.7% in small-cell lung cancer, indicating its potential as a treatment option.

The safety profile of SG was consistent with previous studies, with common treatment-related adverse events including neutropenia (57.8%) and nausea (62.6%), and a notable incidence of grade ≥3 neutropenia in patients with specific genetic variations (UGT1A1∗28 homozygotes).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Bardia, A., Messersmith, WA., Kio, EA., et al.[2021]

In a study of 43 patients with metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan, the median overall survival was 13.1 months, indicating its effectiveness in a real-world setting.

Common adverse events included alopecia, diarrhea, and neutropenia, with 27.9% of patients experiencing Grade 3 neutropenia, highlighting the need for careful management of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of sacituzumab govitecan in patients with metastatic triple-negative breast cancer in real-world settings: first observations from an interdisciplinary breast cancer centre in Germany. Reinisch, M., Bruzas, S., Spoenlein, J., et al.[2023]

Sacituzumab govitecan (IMMU-132) has been shown to prolong progression-free survival in patients with advanced triple-negative breast cancer, indicating its efficacy as a treatment option.

The treatment is well tolerated, resulting in fewer and more manageable side effects compared to traditional irinotecan, suggesting a safer profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An ADC for Triple-Negative Breast Cancer. [2018]

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]

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]

In the KEYNOTE-189 study involving 616 patients with metastatic non-squamous non-small-cell lung cancer, the combination of pembrolizumab and pemetrexed-platinum significantly maintained quality of life (GHS/QOL) scores compared to placebo, with a notable improvement at week 21.

Patients receiving pembrolizumab also experienced a longer median time to deterioration in symptoms like cough and chest pain, although this result was not statistically significant, indicating potential benefits in symptom management with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Garassino, MC., Gadgeel, S., Esteban, E., et al.[2020]

Sacituzumab govitecan (SG) is a promising treatment for metastatic triple-negative breast cancer (mTNBC) that has progressed after first-line therapy, showing significant efficacy as an antibody-drug conjugate targeting Trop-2.

SG has received breakthrough therapy status from the FDA, highlighting its potential as a novel therapeutic option for patients with limited treatment choices in mTNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan: antibody-drug conjugate in triple-negative breast cancer and other solid tumors. Fenn, KM., Kalinsky, K.[2020]

Sacituzumab govitecan, an antibody-drug conjugate targeting TROP-2, shows promise in treating malignant pleural mesothelioma (MPM), particularly in TROP-2-positive cell lines, as it effectively induces cell cycle arrest and cell death.

TROP-2 was expressed in 6 out of 17 MPM cell lines, and sensitivity to the drug SN38 was observed in 10 of these lines, suggesting that TROP-2 expression could serve as a biomarker for selecting patients who may benefit from sacituzumab govitecan therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROP2 expression and SN38 antitumor activity in malignant pleural mesothelioma cells provide a rationale for antibody-drug conjugate therapy. Hegedüs, L., Okumus, Ö., Mairinger, F., et al.[2023]

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, 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]

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]

Sacituzumab govitecan is an antibody-drug conjugate that effectively targets and delivers treatment to Trop-2 expressing cells in patients with metastatic triple negative breast cancer (TNBC), showing promising anti-cancer activity in those who have already undergone at least two prior treatments.

The drug has a manageable safety profile, with common side effects including nausea, neutropenia, and diarrhea, and ongoing studies suggest its efficacy may extend to other types of epithelial cancers beyond TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer. Weiss, J., Glode, A., Messersmith, WA., et al.[2020]

Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, showed promising therapeutic activity in a phase I trial with 25 patients suffering from various metastatic solid cancers, achieving partial responses in two patients and stable disease in 16 others.

The maximum tolerated dose was determined to be 12 mg/kg for the first cycle, with lower doses (8 and 10 mg/kg) being safer for extended treatment, leading to acceptable toxicity levels and disease control for up to 36 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Starodub, AN., Ocean, AJ., Shah, MA., et al.[2022]

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