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NCT Number: NCT07196384

Optical PD-1 and PD-L1 Imaging in Locally Advanced Esophageal Cancer Using Durvalumab-680LT and Nivolumab-800CW

Radiation and chemotherapy can shrink the tumor. For certain types of cancer, immunotherapy is added to further reduce the tumor size. Immunotherapy works for some patients and can sometimes keep the cancer under control for a long time. Unfortunately, immunotherapy does not work for every patient. That's why researchers around the world are looking for new ways to predict who will benefit from immunotherapy and who will not.

It is likely that immunotherapy is more effective when the tumor or immune cells have specific targets, such as the proteins PD-L1 or PD-1. Unfortunately, clinicians cannot reliably detect these proteins through blood tests or tissue samples, because their presence can vary throughout the tumor.

With this study, the investigators hope to use a new technique called 'fluorescence endoscopy' during an endoscopic ultrasound of the esophagus to visualize whether the PD-L1 or PD-1 proteins are present in esophageal cancer or immune cells. Additionally, the investigators aim to investigate whether the presence of these proteins changes before and after chemotherapy and/or radiation. This will help us determine the best timing for measuring these proteins in the future.

What is fluorescence endoscopy? To determine whether the proteins are present, participants in this study will receive two 'tracers' via an IV beforehand. The first tracer is a fluorescent substance-a kind of 'glow-in-the-dark' compound-attached to a drug that binds to PD-L1 proteins in esophageal cancer. The second fluorescent tracer binds to PD-1 proteins on immune cells.

During fluorescence endoscopy, the investigators use special equipment to detect these tracers in the esophagus. This information may help us better identify which patients are suitable for immunotherapy treatment and which are not.

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Key information

Conditions

Esophageal Cancer Digestive System Diseases Digestive System Neoplasms Esophageal Diseases Esophageal Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Neoplasms Neoplasms Neoplasms by Site

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Lesion suspected for locally advanced EC (cT1b-4a N0-3 M0);
  • Indication for neoadjuvant therapy or definitive chemo-radiation therapy;
  • Age ≥ 18 years;
  • Written informed consent.

Exclusion criteria

  • Medical or psychiatric conditions that compromise the patient's ability to give informed consent according to treating medical physician;
  • Concurrent uncontrolled medical conditions according to treating medical physician;
  • Medical history of auto-immune disease and on active treatment;
  • Pregnancy or breast feeding. A negative pregnancy test must be available for women of childbearing potential (i.e. premenopausal women with intact reproductive organs and women less than two years after menopause);
  • Irradical endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of the primary tumor prior to start of neoadjuvant therapy according to the patient's medical history;
  • Received an investigational drug within 30 days prior to the tracer administration according to the patient's medical history;
  • History of infusion reactions to durvalumab or nivolumab or other monoclonal antibodies according to the patient's medical history;

Treatment and study plan

Spectroscopy system

Device

System that measures the fluorescence intensity in tissue in vivo.

Nivolumab-800CW

Drug

Fluorescent tracer

Durvalumab-680LT

Drug

Fluorescent tracer

Primary outcomes

  1. Feasiblity

    Time frame: Up to 14 months

    To determine the feasibility of our newly built dual-wavelength spectroscopy system in combination with the fluorescent tracers durvalumab-680LT and nivolumab-800CW. The spectroscopy system is considered feasible if at least 4 out of 10 patients demonstrate a higher tumor-to-healthy tissue ratio based on spectroscopy measurements. This ratio is calculated by dividing the spectroscopy value of the tumor region by that of the adjacent healthy tissue. The threshold of 4 out of 10 patients was selected based on literature data, which indicate that approximately 43.5% to 48.1% of patients exhibit high PD-1/PD-L1 expression in the tumor area. The investigators therefore expect a similar proportion of patients to show elevated spectroscopy values corresponding to increased target expression.

  2. Safety of dual tracer administratio

    Time frame: Up to 14 months

    • To assess the safety of dual tracer administration of nivolumab-800CW and durvalumab-680LT by evaluating heart rate in beats per minute.

Secondary outcomes

  1. Safety of dual tracer administration

    Time frame: Up to 14 months

    • To assess the safety of dual tracer administration of nivolumab-800CW and durvalumab-680LT by evaluating blood pressure in mmHg

  2. Safety of dual tracer administration

    Time frame: Up to 14 months

    To assess the safety of dual tracer administration of nivolumab-800CW and durvalumab-680LT by evaluating number of AE's

  3. Safety of dual tracer administration

    Time frame: Up to 14 months

    To assess the safety of dual tracer administration of nivolumab-800CW and durvalumab-680LT by evaluating number of SAE'S

  4. Safety of dual tracer administration

    Time frame: Up to 14 months

    To assess the safety of dual tracer administration of nivolumab-800CW and durvalumab-680LT by evaluating number of SUSARS.

  5. Correlation between in vivo signal and ex vivo pathology

    Time frame: Up to 14 months

    • To investigate the correlation between fluorescence signals detected in vivo with ex vivo histopathology, immunohistochemistry; This correlation will be measured by comparing the percentage of staining on immunohistochemistry staining and the hight of the fluorescence signals detected in vivo (unit: Q • μfa,x).

  6. Correlation of fluorescence intensity before and after neoadjuvant therapy

    Time frame: Up to 14 months

    • To compare the fluorescence intensity of the fluorescent tracer durvalumab-680LT and nivolumab-800CW before and after neoadjuvant therapy. These measurements will be taken with a spectroscopy device at two different time points. The first before neoadjuvant treatment, the second after neoadjuvant treatment. The unit of the fluorescence intensity is Q • μfa,x. Both measurements will be compared with each other.

  7. Correlation between in vivo signal and ex vivo analysis

    Time frame: Up to 14 months

    • To compare fluorescence signals detected in vivo taken with a spectroscopy device during study-specific procedures with the percentage of fluorescence staining assessed by fluorescence microscopy

  8. Investigate the sub-cellular location of the drugs.

    Time frame: Up to 14 months

    • To assess the (sub)-cellular location and distribution of durvalumab-680LT and nivolumab-800CW by ex vivo fluorescence microscopy. The investigators image a slide of a biopsy block with the fluorescence microscope, after imaging the investigators introduce fluorescence markers targeting certain cell types on the same slide. These slides can be imaged with the fluorescence microscope again. Afterwards the two slides can be compared with each other to look for overlap.

  9. Optimal dose determination of nivolumab-800CW

    Time frame: up to 12 months

    • To determine the most optimal dose of nivolumab-800CW for fluorescence molecular endoscopy.

Sponsors and collaborators

Lead sponsor

University Medical Center Groningen

Other

Collaborators

  • Martini Hospital Groningen

Registry information

Official study title

Optical PD-1 and PD-L1 Imaging Using Dual-wavelength Quantitative Fluorescence Endoscopy in Locally Advanced Esophageal Cancer Using Durvalumab-680LT and Nivolumab-800CW

Acronym: GLOW

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Sep 29, 2025
Registry last updated
Nov 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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