Nivolumab for Esophageal Cancer

(CheckMate 577 Trial)

Recruiting at 403 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Disqualifiers: Cervical carcinoma, Stage IV, others

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: Unknown

Duration: 46 months

794 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if Nivolumab, a drug that helps the immune system fight cancer, can help cancer patients stay free of the disease longer. Nivolumab has been shown to improve survival in various cancers, including melanoma and esophageal cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Nivolumab for esophageal cancer?

Research shows that Nivolumab improves disease-free survival in patients with resected esophageal or gastroesophageal junction cancer, extending it to 22.4 months compared to 11.0 months with a placebo. Additionally, Nivolumab has shown long-term effectiveness in Japanese patients with advanced esophageal cancer, with a median overall survival of 10.78 months. ^{1 2 3 4 5}

Is Nivolumab safe for treating esophageal cancer?

Nivolumab is generally considered safe for treating esophageal cancer, but it can cause some side effects. In studies, fewer patients experienced severe side effects with Nivolumab compared to standard chemotherapy, though there is a risk of esophageal fistula (an abnormal connection in the esophagus) and a higher chance of pneumonitis (lung inflammation) in esophageal cancer patients. ^{1 5 6 7 8}

How does the drug Nivolumab differ from other treatments for esophageal cancer?

Nivolumab is unique because it is an immunotherapy drug that works by blocking a protein called PD-1, which helps the immune system attack cancer cells more effectively. Unlike traditional chemotherapy, which directly kills cancer cells, Nivolumab enhances the body's immune response to fight the cancer, and it has shown improved survival rates in patients with esophageal cancer compared to standard treatments. ^{1 2 3 5 9}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for people who've had surgery for Stage II/III esophageal or gastroesophageal junction cancer and still have some signs of the disease. They must have finished chemo radiotherapy before surgery. It's not open to those with other conditions that could interfere.

Inclusion Criteria

I had surgery for cancer with clear margins but still have some disease left.

I finished chemo and radiation before surgery.

My cancer is in the esophagus or where the stomach meets the esophagus, and it's at an advanced stage but not the most severe.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Nivolumab or placebo to assess disease-free survival

46 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

46 months

Treatment Details

Interventions

• Nivolumab
• Placebo

Trial Overview The study is testing if Nivolumab, an immune therapy drug, can keep cancer from coming back better than a placebo (a treatment with no active drug). Participants will be randomly assigned to receive either Nivolumab or the placebo.

Participant Groups

Group I: Nivolumab Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Ono Pharmaceutical Co. Ltd

Industry Sponsor

Trials

182

Recruited

97,100+

Shinji Takai

Ono Pharmaceutical Co. Ltd

Chief Medical Officer since 2023

MD from an unspecified institution

Gyo Sagara

Ono Pharmaceutical Co. Ltd

Chief Executive Officer since 2024

PhD in Pharmaceutical Sciences from Kyoto University

Findings from Research

Nivolumab and pembrolizumab, both PD-1 inhibitors, have shown significant improvements in overall survival (OS) for patients with esophageal carcinoma, particularly in combination with chemotherapy or ipilimumab, based on multiple landmark trials.

In the second-line treatment setting, monotherapy with nivolumab, pembrolizumab, and other PD-1 inhibitors also demonstrated improved OS compared to traditional chemotherapy, highlighting the effectiveness of immunotherapy in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in Squamous Cell Cancer of the Esophagus. Thuss-Patience, P., Stein, A.[2022]

In a study of 58 esophageal squamous cell carcinoma (ESCC) patients treated with nivolumab after chemotherapy failure, the objective response rate was 19.3%, with a median response duration of 6.5 months, indicating that nivolumab can be an effective second-line therapy.

Patients with higher PD-L1 expression (CPS ≥ 20) experienced significantly longer progression-free survival (7.5 months) compared to those with lower expression, suggesting that PD-L1 levels may help predict treatment outcomes with nivolumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for esophageal squamous cell carcinoma and the predictive role of PD-L1 or CD8 expression in its therapeutic effect. Lee, J., Kim, B., Jung, HA., et al.[2021]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A population-based study in resected esophageal or gastroesophageal junction cancer aligned with CheckMate 577. [2022]

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

Long-term efficacy and predictive correlates of response to nivolumab in Japanese patients with esophageal cancer. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy in Squamous Cell Cancer of the Esophagus. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

Exploration of predictors of benefit from nivolumab monotherapy for patients with pretreated advanced gastric and gastroesophageal junction cancer: post hoc subanalysis from the ATTRACTION-2 study. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Nivolumab for esophageal squamous cell carcinoma and the predictive role of PD-L1 or CD8 expression in its therapeutic effect. [2021]

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

Efficacy and safety of Nivolumab in patients with advanced esophageal, gastroesophageal, and gastric cancers: a meta-analysis of randomized controlled trials. [2023]

7. 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]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of Nivolumab in the Treatment of Resected Esophageal Squamous Cell Carcinoma: A Review of the Clinical Data. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. [2023]