Sacituzumab + Pembrolizumab + Chemotherapy for Esophageal Cancer

Recruiting at 54 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: CYP3A4 inducers/inhibitors, Immunosuppressants

Disqualifiers: Squamous cell cancer, Severe dry eye, Cardiovascular disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: 6

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced esophageal cancer that cannot be surgically removed. Researchers aim to determine if adding sacituzumab tirumotecan (an experimental treatment) to standard chemotherapy and the immune therapy pembrolizumab is safe and effective. The trial consists of two parts: first assessing safety, then evaluating effectiveness. Suitable participants have untreated esophageal cancer and are unlikely to require surgery soon. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain medications like strong inducers/inhibitors of CYP3A4 or if you have received certain treatments recently. It's best to discuss your specific medications with the trial team.

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

Research shows that pembrolizumab is generally well-tolerated by patients, causing manageable side effects. Common side effects include tiredness and skin rash, while serious side effects are less common.

Sacituzumab tirumotecan, a newer drug, is still under study for safety. In a previous study, it showed promise in treating breast cancer. Patients generally tolerated it well, with some experiencing nausea and hair loss. This study aims to test its safety when combined with pembrolizumab and chemotherapy for esophageal cancer.

The chemotherapy drugs in this trial, such as capecitabine and 5-FU, are already used to treat cancer. They have known side effects, like low blood counts and mouth sores, but doctors monitor these closely.

Overall, this trial is in its early stages and focuses on safety. The goal is to determine how well patients tolerate this combination of treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for esophageal cancer because they combine existing therapies with innovative approaches. Sacituzumab tirumotecan, a key player here, is an antibody-drug conjugate that specifically targets and delivers chemotherapy directly to cancer cells, potentially reducing side effects and improving effectiveness. This differs from traditional chemotherapy, which affects both cancerous and healthy cells indiscriminately. Meanwhile, pembrolizumab, an immunotherapy, helps the immune system better recognize and attack cancer cells. This combination aims to enhance treatment outcomes by merging targeted therapy with immune system support, setting it apart from the standard chemotherapy regimens commonly used today.

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

This trial will compare two treatment arms for esophageal cancer. In one arm, participants will receive Pembrolizumab plus Chemotherapy. In the other arm, participants will receive Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy.

Studies have shown that sacituzumab tirumotecan, when used alone, can significantly improve progression-free survival and overall survival in certain cancers. Research indicates that combining sacituzumab tirumotecan with pembrolizumab has yielded promising results in other cancers, such as advanced prostate cancer resistant to hormone therapy. This suggests potential effectiveness for esophageal cancer as well. Pembrolizumab, an immunotherapy, helps the immune system target cancer cells. Chemotherapy, which directly attacks cancer cells, may enhance these effects. Together, this combination of treatments aims to combat the cancer in multiple ways. ^{1 3 5 6 7}

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 advanced gastroesophageal adenocarcinoma that can't be surgically removed or has spread, and who haven't had previous systemic therapy for it. They should have a life expectancy of at least 6 months, an ECOG performance status of 0 or 1 (meaning they are fully active or restricted in physically strenuous activity but ambulatory), and must have recovered from major side effects of prior therapies.

Inclusion Criteria

My side effects from past cancer treatments have mostly gone away.

My cancer is not HER2 positive.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I am currently being treated for an infection.

Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration

I have an immune system disorder or have been on steroids or other immune-weakening medicines recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Evaluate the safety and tolerability, and establish a recommended Phase 2 dose (RP2D) for sacituzumab tirumotecan in combination with chemotherapy and immunotherapy

4 weeks

Efficacy

Participants receive sacituzumab tirumotecan with pembrolizumab and chemotherapy to evaluate efficacy

Up to 2 years

Every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 55 months

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Pembrolizumab
• Sacituzumab Tirumotecan

Trial Overview The study tests Sacituzumab Tirumotecan combined with Pembrolizumab and chemotherapy drugs like Leucovorin, Capecitabine, Levoleucovorin, and 5-FU in patients with certain types of stomach cancer. It's divided into two phases: first to check safety and tolerability (and find the best dose), then to assess how effective this combination is.

How Is the Trial Designed?

Group I: Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy Experimental Treatment 4 Interventions

Participants will receive sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 6 week cycle until discontinuation, pembrolizumab 400 mg via IV injection on day 1 of every 6 week cycle for up to 18 cycles (up to \~2 years) AND investigator's choice of capecitabine 1000 mg/m\^2 orally twice daily for 14 days Q3W OR 5-FU 400 mg/\^2 via bolus IV plus 2400 mg/m\^2 continuous IV once Q2W.

Group II: Pembrolizumab plus Chemotherapy Active Control 5 Interventions

Participants will receive pembrolizumab 400 mg via intravenous (IV) injection on day 1 of every 6 week cycle for up to 18 cycles (up to \~2 years) AND investigator's choice of CAPOX chemotherapy (capecitabine 1000 mg/m\^2 orally twice daily for 14 days every 3 weeks (Q3W) and oxaliplatin 130 mg/m\^2 via IV infusion Q3W) OR mFOLFOX6 chemotherapy (oxaliplatin 85 mg/m\^2 via IV infusion Q3W; 5-FU 400 mg/\^2 via bolus IV plus 2400 mg/m\^2 continuous IV once every 2 weeks (Q2W); and leucovorin 400 mg/m\^2 via IV infusion Q2W OR levoleucovorin 200 mg/m\^2 Q2W).

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

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) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

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]

In a study of 55 patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC), pembrolizumab combined with chemotherapy or radiotherapy showed favorable long-term survival outcomes, with a 12-month overall survival rate of 78.8%.

The treatment was found to be safe and manageable, with long-term adverse effects reported in only a small number of patients, indicating that pembrolizumab is a promising option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and predictors of pembrolizumab-based regimens in patients with advanced esophageal cancer in the real world. Wang, HC., Huang, X., Chen, J., et al.[2023]

Biologic therapies, particularly those targeting HER2 and VEGF, are showing promise in treating esophageal and gastric cancers, with trastuzumab and ramucirumab currently recommended by the NCCN for specific patient groups.

Recent studies indicate that other agents like pertuzumab, apatinib, and pembrolizumab may improve overall and progression-free survival, suggesting a growing role for targeted biologic therapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. Samson, P., Lockhart, AC.[2020]

The combination of panitumumab and irinotecan was found to be ineffective for treating advanced esophageal adenocarcinoma, with only a 6% partial response rate among 18 evaluable patients in the study.

Despite some patients experiencing stable disease, the overall survival was limited, with a median of only 7.2 months, indicating that this treatment regimen does not provide significant clinical benefit for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Irinotecan Plus Panitumumab as Second-Line Therapy for Patients with Advanced Esophageal Adenocarcinoma. Yoon, H., Karapetyan, L., Choudhary, A., et al.[2019]

In a phase 3 study involving 749 patients, pembrolizumab combined with chemotherapy significantly improved overall survival compared to chemotherapy alone in patients with advanced oesophageal squamous cell carcinoma, particularly those with a PD-L1 combined positive score (CPS) of 10 or more, with median survival times of 13.9 months versus 8.8 months.

Pembrolizumab plus chemotherapy also enhanced progression-free survival, showing a median of 7.5 months compared to 5.5 months for the placebo group, while maintaining a manageable safety profile with similar rates of severe treatment-related adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Sun, JM., Shen, L., Shah, MA., et al.[2021]

The study found that using 89Zr-trastuzumab PET and ctDNA monitoring can help identify early signs of treatment resistance in patients with HER2-positive metastatic esophagogastric cancer, potentially guiding treatment adjustments.

Patients with ERBB2 amplification showed improved progression-free survival (PFS), while those with alterations in MYC and CDKN2A/B had worse PFS, indicating that specific genetic markers can predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer. Maron, SB., Chatila, W., Walch, H., et al.[2023]

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 a study of 39 patients with locally advanced esophageal squamous cell carcinoma (ESCC), pembrolizumab combined with neoadjuvant chemotherapy resulted in a high objective response rate of 87.2% and a disease control rate of 100%.

The treatment led to significant surgical outcomes, with a major pathological response rate of 68.2% and a complete pathological response rate of 45.5% among those who underwent radical surgery, while maintaining a manageable safety profile with only 15.4% experiencing severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab combined with paclitaxel and platinum as induction therapy for locally advanced esophageal squamous cell carcinoma: a retrospective, single-center, three-arm study. Lin, W., Huang, Y., Zhu, L., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06469944

Substudy 06C: A Study of Sacituzumab Tirumotecan (MK- ... This is a phase 1/2, multicenter, open-label umbrella platform study that will evaluate the safety and tolerability of sacituzumab tirumotecan with ...

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

A phase 3, randomized study of adjuvant sacituzumab ... In a prior phase 3 study (OptiTROP-Breast01), sac-TMT alone improved PFS (HR, 0.31; 95% CI, 0.22-0.45; P < 0.00001) and OS (HR, 0.53; 95% CI, ...

3. 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 ...

4. cancernetwork.com cancernetwork.com/view/sac-tmt-combo-produces-encouraging-activity-in-pretreated-metastatic-crpc

Sac-TMT Combo Produces Encouraging Activity in ... Data from a phase 2 study support further development of sacituzumab tirumotecan plus pembrolizumab in metastatic castration-resistant ...

5. merckclinicaltrials.com merckclinicaltrials.com/trial/nct06469944/

Substudy 06C: A Study of Sacituzumab Tirumotecan With ... This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS511

KEYMAKER-U06: Phase 1/2 umbrella platform study of ... Both substudies will have a safety lead-in phase of ≤10 patients to determine the recommended phase 2 dose of sacituzumab tirumotecan when used ...

7. merck.com merck.com/news/merck-to-present-survival-data-and-new-research-on-10-investigational-or-approved-medicines-at-esmo-congress-2024/

Merck to Present Survival Data and New Research on 10 ... Overall survival (OS) data for KEYTRUDA ® (pembrolizumab) in earlier stages of women's cancers, including high-risk early-stage ...