Testing a new cancer drug for advanced esophageal cancer

Plain-English translation of NCT06644781 on ClinicalTrials.gov ↗ · Source last updated January 2026 · Translation generated July 2026 · How we translate trials

Phase 3 — Testing in thousands of people, comparing the treatment against what doctors currently use. This is the last big step before approval.

What is this trial?

This study is testing a new cancer drug called (I-DXd) to see if it can help people with advanced esophageal squamous cell carcinoma live longer than those who receive standard chemotherapy options. The medication works by targeting a specific protein on cancer cells and delivering medicine directly to them. About 510 people will participate, with half receiving the new medication and half receiving one of three standard chemotherapy drugs, chosen by their doctor.

People with advanced esophageal cancer that has grown after prior chemotherapy and immunotherapy treatments have very limited options. Researchers believe this medication might be more effective because it targets cancer cells in a different way, potentially offering better survival and fewer side effects than current standard treatments.

Do you qualify?

You likely qualify if…

you are at least 18 years old
you have been diagnosed with advanced or metastatic esophageal squamous cell carcinoma that cannot be surgically removed
your cancer has gotten worse after treatment with platinum-based chemotherapy and immunotherapy, and you have received no more than one prior chemotherapy regimen
you have tumor samples available that doctors can test
you have at least one measurable tumor lesion visible on a CT or MRI scan
you are in generally good health with an ECOG performance status of 0 or 1

You likely don't qualify if…

you have previously received this medication or other B7-H3 targeted drugs
you have previously received topoisomerase inhibitor drugs
your cancer is a subtype called adenosquamous carcinoma
you have untreated brain metastases, spinal cord compression, or cancer in the fluid around your brain that is causing symptoms
your tumor is invading nearby vital organs like the aorta or lungs in a way that puts you at high risk for serious bleeding or fistula

What participation looks like

If you join this trial, you will be randomly assigned to receive either the new medication (intravenous infusion every 3 weeks) or one of three standard chemotherapy drugs, also given intravenously every 3 weeks. You will have regular doctor visits, imaging scans to measure your tumor, and blood tests to monitor your health and how you are responding to treatment. The study will follow you to see how long you live and how well the medication controls your cancer compared to standard chemotherapy.

AI-generated summary from trial data · Jul 3, 2026 · Not medical advice

Trial locations(88 sites)

United States

Providence Medical Foundation, Fullerton, California

Henry Ford Health System, Detroit, Michigan

Baptist Cancer Center, Memphis, Tennessee

SCRI Oncology Partners, Nashville, Tennessee

John Peter Smith Hospital, Fort Worth, Texas