Pembrolizumab + Chemotherapy for Esophageal Cancer

Recruiting at 3 trial locations

Overseen By Carina Puello, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Metastatic disease, Active TB, Autoimmune, others

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

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

42 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if adding pembrolizumab to standard treatments can help patients with advanced esophageal cancer. Pembrolizumab boosts the immune system to better fight cancer. The goal is to see if this combination improves patient outcomes. Pembrolizumab has been used in various cancers, including melanoma, lung cancer, and head and neck cancer, showing durable responses and significant advancements in treatment options.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop these at least 7 days before starting the trial treatment.

What data supports the effectiveness of the drug Pembrolizumab combined with chemotherapy for esophageal cancer?

Pembrolizumab combined with chemotherapy has been shown to be effective as a first-line therapy for patients with advanced esophageal cancer, and it has been approved for treating metastatic or locally advanced esophageal or gastroesophageal junction cancer. ^{1 2 3 4 5}

Is the combination of pembrolizumab and chemotherapy safe for treating esophageal cancer?

Pembrolizumab, also known as Keytruda, has been studied for safety in combination with chemotherapy for esophageal cancer. Research has shown it to be generally safe, with ongoing studies further confirming its safety when used before surgery in esophageal cancer patients. ^{1 2 6 7 8}

How is the drug pembrolizumab combined with chemotherapy unique for treating esophageal cancer?

Pembrolizumab combined with chemotherapy is unique because it is approved for use in advanced esophageal cancer, offering a new option that targets the immune system to help fight cancer cells, unlike traditional chemotherapy alone. This combination is particularly notable for its use regardless of PD-L1 expression, which is a protein that can affect how well the immune system can attack cancer cells. ^{1 2 4 9 10}

Research Team

Manish Shah, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for adults over 18 with locally advanced esophageal adenocarcinoma, who haven't had prior cancer treatments for their current diagnosis. They must have certain blood cell counts and organ function levels, be willing to provide tissue samples, and agree to use birth control. Exclusions include active infections, other recent cancers except some skin or prostate cancers, autoimmune diseases needing treatment in the last 2 years, known HIV or hepatitis B/C.

Inclusion Criteria

I am using two birth control methods or am not having sex to join this study.

Platelets≥100,000 / mcL

Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion within 7 days of assessment

Exclusion Criteria

I have not received a live vaccine within the last 30 days, except for the flu shot.

I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

I have or had lung inflammation not caused by an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive induction chemotherapy with taxol/carboplatin

6-8 weeks

Chemoradiation

Participants receive weekly chemoradiation with taxol/carboplatin and pembrolizumab

6-8 weeks

Surgery

Participants undergo surgery following chemoradiation

1 week

Adjuvant Pembrolizumab

Pembrolizumab is administered every 3 weeks for 1 year post-surgery

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Pembrolizumab
• Taxol and Carboplatin

Trial Overview The study tests Pembrolizumab combined with chemotherapy (Taxol and Carboplatin) and chemoradiation on patients with esophageal adenocarcinoma. It's a phase II trial aiming to see how safe this combination is and how well it works by looking at disease-free survival after one year.

Participant Groups

Group I: Cohort 2 Experimental Treatment 3 Interventions

Subjects in Cohort 2 receive pembrolizumab along with induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion.

Group II: Cohort 1 Experimental Treatment 3 Interventions

Subjects in Cohort 1 receive conventional induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion.

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?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Merck Sharp & Dohme LLC

Industry 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]

Preoperative treatment with pembrolizumab combined with chemoradiotherapy was found to be safe for 20 patients with resectable esophageal squamous cell carcinoma, with a high pathologic complete response (pCR) rate of 55.6%.

Despite some patients experiencing significant adverse events, including grade III lymphopenia in 65% of cases, the treatment did not delay surgery, indicating its feasibility for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). Li, C., Zhao, S., Zheng, Y., et al.[2021]

In a meta-analysis of 1231 patients, pembrolizumab and paclitaxel showed no significant difference in effectiveness for treating advanced gastroesophageal cancer, with similar objective response rates.

Both treatments can be considered viable options for patients, as they provide comparable time to response and similar rates of partial response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus paclitaxel for previously treated, advanced gastro-esophageal junction cancer: A systematic review and meta-analysis of randomized clinical trials. Swed, S., Shaheen, N., Hafez, W., 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]

Nivolumab (OPDIVO) was approved by the FDA for treating unresectable advanced esophageal squamous cell carcinoma (ESCC) after prior chemotherapy, showing a significant improvement in overall survival (10.9 months for nivolumab vs. 8.4 months for chemotherapy).

Patients treated with nivolumab experienced fewer treatment-emergent adverse events compared to those receiving chemotherapy, although there was a new risk of esophageal fistula and a higher incidence of pneumonitis in the ESCC population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-Risk Summary of Nivolumab for the Treatment of Patients with Unresectable Advanced, Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma After Prior Fluoropyrimidine- and Platinum-Based Chemotherapy. Pelosof, L., Saung, MT., Donoghue, 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]

A post hoc analysis of the JUPITER-06 study demonstrated that adding PD-1 antibodies (like pembrolizumab or nivolumab) to chemotherapy significantly improves overall survival and progression-free survival in patients with advanced esophageal squamous cell carcinoma (ESCC), even in those with low PD-L1 expression (TPS < 1%).

The study found that patients with low PD-L1 expression also experienced a notable increase in objective response rates when treated with PD-1 antibodies plus chemotherapy, indicating that this combination therapy is effective regardless of PD-L1 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Benefit of First-Line Programmed Death-1 Antibody Plus Chemotherapy in Low Programmed Cell Death Ligand 1-Expressing Esophageal Squamous Cell Carcinoma: A Post Hoc Analysis of JUPITER-06 and Meta-Analysis. Wu, HX., Pan, YQ., He, Y., et al.[2023]

References

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). [2021]

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

Pembrolizumab versus paclitaxel for previously treated, advanced gastro-esophageal junction cancer: A systematic review and meta-analysis of randomized clinical trials. [2022]

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

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

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

Benefit-Risk Summary of Nivolumab for the Treatment of Patients with Unresectable Advanced, Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma After Prior Fluoropyrimidine- and Platinum-Based Chemotherapy. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial design. [2022]

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

Clinical Benefit of First-Line Programmed Death-1 Antibody Plus Chemotherapy in Low Programmed Cell Death Ligand 1-Expressing Esophageal Squamous Cell Carcinoma: A Post Hoc Analysis of JUPITER-06 and Meta-Analysis. [2023]

10. England pubmed.ncbi.nlm.nih.gov

KEYNOTE-590: Phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer. [2019]