Pembrolizumab + Chemotherapy for Esophageal Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with locally advanced esophageal adenocarcinoma, a type of cancer in the esophagus. Researchers aim to determine if combining pembrolizumab (a medication that helps the immune system fight cancer) with chemotherapy and radiation is safe and effective. Participants are divided into two groups: both receive conventional chemotherapy and radiation, but one group receives pembrolizumab throughout the entire treatment. Individuals with confirmed esophageal adenocarcinoma who are eligible for surgery may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that pembrolizumab, combined with chemotherapy drugs like Taxol and Carboplatin, is generally well-tolerated by patients with esophageal cancer. One study found that this combination helped patients with advanced esophageal cancer live longer. Another study indicated that most patients managed the treatment's side effects, which were not too severe.

Common side effects include tiredness and nausea, typical for most cancer treatments. Importantly, pembrolizumab is already approved for other conditions like lung cancer, indicating a known safety record. Overall, these findings suggest that previous studies have considered the treatment safe and well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab with chemotherapy for esophageal cancer because it represents a promising shift from traditional treatments. Unlike the standard of care, which typically involves surgery and chemotherapy or chemoradiation alone, this approach integrates pembrolizumab, an immunotherapy drug. Pembrolizumab works by targeting and blocking the PD-1 pathway, which can help the immune system better recognize and attack cancer cells. This combination aims to enhance the effectiveness of chemotherapy, potentially leading to better outcomes. By leveraging the body's own immune response, this treatment offers hope for improved survival rates and quality of life for patients.

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

Research shows that pembrolizumab, when combined with chemotherapy, effectively treats esophageal cancer. In this trial, participants in Cohort 1 will receive conventional induction chemotherapy with Taxol and Carboplatin, followed by weekly chemoradiation with pembrolizumab. Studies indicate that pembrolizumab can slow the disease more effectively than chemotherapy alone, with a hazard ratio of 0.85. It also achieves a 60.9% overall response rate and extends patient survival. The combination of Taxol and Carboplatin, administered to participants in both cohorts, is also effective, with a 54% overall response rate and is generally well-tolerated. Together, these treatments offer hope for fighting esophageal cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Manish Shah, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

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 been diagnosed with HIV.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38077159/

Long-term efficacy and predictors of pembrolizumab-based ... Pembrolizumab combined with chemotherapy or radiotherapy resulted in favorable long-term survival in patients with locally advanced or metastatic ESCC.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.438

Efficacy of pembrolizumab in advanced esophageal ... Pembrolizumab use in EC showed a reduced risk of disease progression vs chemotherapy alone [HR: 0.85 (CI: 0.75-0.96) (p < 0.05)] and a 21% ...

3. onclive.com onclive.com/view/dr-shah-on-5-year-outcomes-with-pembrolizumab-chemo-in-esophageal-cancer

Dr Shah on 5-Year Outcomes With Pembrolizumab/Chemo ... The median progression-free survival (PFS) was 6.3 months (95% CI, 6.2-7.1) with pembrolizumab vs 5.8 months (95% CI, 5.0-6.0) with placebo (HR, ...

4. merck.com merck.com/news/mercks-keytruda-pembrolizumab-significantly-improved-overall-survival-os-compared-to-chemotherapy-in-patients-with-advanced-esophageal-or-esophagogastric-junction-carcinoma-whose-tu/

Merck's KEYTRUDA® (pembrolizumab) Significantly ... “In this pivotal trial, KEYTRUDA resulted in a statistically significant and clinically meaningful improvement over standard chemotherapy in overall survival ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11574897/

Effectiveness and safety of first-line pembrolizumab plus ... In general, pembrolizumab plus chemotherapy led to a high ORR (60.9%) and a median PFS and OS of 10.8 and 17.3 months, respectively, with a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9830331/

Pembrolizumab combined with paclitaxel and platinum as ... Pembrolizumab has been shown to have a powerful benefit for locally advanced or metastatic esophageal cancer. The aim of present study was ...

7. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... KEYTRUDA plus carboplatin-paclitaxel or nab-paclitaxel reduced the risk of death by 29% (HR=0.71 [95% CI, 0.59-0.85]) versus chemotherapy alone. The median OS ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.4088

A prospective phase 2 single-arm study to evaluate ... Neoadjuvant treatment with combination pembrolizumab and chemotherapy demonstrated encouraging anti-tumor activities, good surgical outcomes and a manageable ...

9. onclive.com onclive.com/view/pembrolizumab-plus-chemotherapy-elicits-continued-survival-benefit-in-advanced-esophageal-cancer

Pembrolizumab Plus Chemotherapy Elicits Continued ... Combined treatment with pembrolizumab (Keytruda) and chemotherapy has been shown to promote longevity in patients with advanced esophageal cancer.

10. cardiothoracicsurgery.biomedcentral.com cardiothoracicsurgery.biomedcentral.com/articles/10.1186/s13019-024-02500-9

Study on the efficacy and safety of neoadjuvant ... In the KEYNOTE-181 study, Pembrolizumab was found to be superior to chemotherapy in patients with advanced esophageal cancer, with PD-L1 ≥ 10 ...