Sacituzumab + Pembrolizumab + Chemotherapy for Esophageal Cancer

Recruiting at 43 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

Trial Summary

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.

What data supports the effectiveness of the drug combination Sacituzumab, Pembrolizumab, and Chemotherapy for treating esophageal cancer?

Pembrolizumab, one of the drugs in the combination, has been shown to be effective when used with chemotherapy for advanced esophageal cancer, improving survival rates. Additionally, pembrolizumab has been approved for use in esophageal cancer, indicating its effectiveness in this context. ^{1 2 3 4 5}

Is the combination of Sacituzumab, Pembrolizumab, and Chemotherapy safe for humans?

Pembrolizumab (Keytruda) has been approved for use in esophageal cancer and has shown clinical activity in various solid tumors, indicating it is generally considered safe for human use. However, specific safety data for the combination with Sacituzumab and chemotherapy in esophageal cancer is not provided in the available research. ^{1 2 6 7 8}

What makes the drug combination of Sacituzumab, Pembrolizumab, and Chemotherapy unique for esophageal cancer?

This treatment is unique because it combines Sacituzumab, an antibody-drug conjugate that targets cancer cells, with Pembrolizumab, an immunotherapy that helps the immune system attack cancer, and chemotherapy, which kills fast-growing cells. This combination aims to enhance the effectiveness of treatment by using different mechanisms to target the cancer. ^{1 2 4 5 9}

What is the purpose of this trial?

This is a phase 1/2, multicenter, open-label umbrella platform study that will evaluate the safety and tolerability of sacituzumab tirumotecan with pembrolizumab and fluoropyrimidine chemotherapy for the first-line (1L) treatment of participants with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma. 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, and to establish a recommended Phase 2 dose (RP2D) for sacituzumab tirumotecan in combination with chemotherapy and immunotherapy. There is no formal hypothesis in this study.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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 haven't had major heart or brain vessel issues in the last 6 months.

I have not received a live vaccine in the last 30 days.

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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 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 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]

References

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

2. China pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020]

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

Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer. [2023]

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

Long-term efficacy and predictors of pembrolizumab-based regimens in patients with advanced esophageal cancer in the real world. [2023]

5. China 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

Phase II Study of Irinotecan Plus Panitumumab as Second-Line Therapy for Patients with Advanced Esophageal Adenocarcinoma. [2019]

8. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

9. England 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. [2021]