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

NCT07196384 | Not Yet Recruiting Phase 1

• 2 other identifiers: UMCG 211642024-520090-12-00
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Esophageal Cancer

Outcome Measures

Primary Outcomes (2)

• Feasiblity

  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.

  Up to 14 months

• Safety of dual tracer administratio

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

  Up to 14 months

Secondary Outcomes (9)

• Safety of dual tracer administration

  Up to 14 months

• Safety of dual tracer administration

  Up to 14 months

• Safety of dual tracer administration

  Up to 14 months

• Safety of dual tracer administration

  Up to 14 months

• Correlation between in vivo signal and ex vivo pathology

  Up to 14 months

Study Arms (2)

25 mg durvalumab-680LT + 15 mg nivolumab-800CW in esophageal cancer

EXPERIMENTAL

Device: Spectroscopy system; Drug: Nivolumab-800CW; Drug: Durvalumab-680LT

25 mg durvalumab-680LT + 25 mg nivolumab-800CW in esophageal cancer

EXPERIMENTAL

Device: Spectroscopy system; Drug: Nivolumab-800CW; Drug: Durvalumab-680LT

Interventions

Spectroscopy system DEVICE

System that measures the fluorescence intensity in tissue in vivo.

25 mg durvalumab-680LT + 15 mg nivolumab-800CW in esophageal cancer; 25 mg durvalumab-680LT + 25 mg nivolumab-800CW in esophageal cancer

Nivolumab-800CW DRUG

Fluorescent tracer

25 mg durvalumab-680LT + 15 mg nivolumab-800CW in esophageal cancer; 25 mg durvalumab-680LT + 25 mg nivolumab-800CW in esophageal cancer

Durvalumab-680LT DRUG

Fluorescent tracer

25 mg durvalumab-680LT + 15 mg nivolumab-800CW in esophageal cancer; 25 mg durvalumab-680LT + 25 mg nivolumab-800CW in esophageal cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Martini Hospital Groningen: collaborator

MeSH Terms

Conditions

Esophageal Neoplasms

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2025
• First Posted: September 29, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: November 21, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share