NCT04757363

A Phase II Study of Nivolumab in Combination With FOLFOX and Regorafenib in Patients With HER2-Negative Metastatic Esophagogastric Cancer

Active, enrolled Phase 2 Last updated 2 March 2026

What this trial tests

Phase 2 trial testing regorafenib in Esophagogastric Cancer in 39 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

11 February 2021

Primary endpoint
1 February 2027

1 February 2027

Quick facts

Lead sponsor	Memorial Sloan Kettering Cancer Center
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	39
Start date	11 February 2021
Primary completion	1 February 2027
Estimated completion	1 February 2027
Sites	7 locations across United States

Drugs / interventions tested

• regorafenib — full drug profile →
• nivolumab (nivolumab) — full drug profile →
• FOLFOX chemotherapy with oxaliplatin — full drug profile →

Conditions studied

• Esophagogastric Cancer — all drugs for Esophagogastric Cancer →
• HER2-Negative — all drugs for HER2-Negative →

Sponsor

Memorial Sloan Kettering Cancer Center — full company profile →

Who can join

18 and older, any sex, with Esophagogastric Cancer or HER2-Negative. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 6-month progression free Survival
  Time frame: 6 months
  will be defined according to RECIST 1.1.

Sponsor's own description

The purpose of this study is to find out whether combining nivolumab, FOLFOX, and regorafenib may be a safe and effective treatment for people who have HER2-negative metastatic esophagogastric cancer.

Nivolumab is an antibody, like the proteins made by the immune system to protect the body from harm. Nivolumab blocks the protein PD-1 (programmed cell death receptor-1) that usually acts as a "brake" on the immune system. Blocking this protein is like releasing the brakes, so that the immune system can target cancer cells and destroy them.

FOLFOX is a combination of three standard chemotherapy drugs (leucovorin, 5-fluorouracil, and oxaliplatin) commonly used to treat your type of cancer. The drugs work by damaging the DNA in cancer cells, which can cause the cells to stop growing and die.

Regorafenib is a type of drug called a tyrosine kinase inhibitor (TKI). This drug targets the tyrosine kinase protein found in or on the surface of cancer cells that the cells need to survive and grow. Blocking this protein may stop cancer cells from growing, or cause them to grow more slowly or to shrink.

The study researchers think that combining nivolumab, FOLFOX, and regorafenib may be a more effective treatment for HER2-negative metastatic esophagogastric cancer than the usual chemotherapy treatment(s) alone.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Neoadjuvant immunotherapy for resectable esophageal cancer: A review.
   Li Q, Liu T, Ding Z. · · 2022 · cited 43× · PMID 36569908 · DOI 10.3389/fimmu.2022.1051841
2. First-line regorafenib with nivolumab and chemotherapy in advanced oesophageal, gastric, or gastro-oesophageal junction cancer in the USA: a single-arm, single-centre, phase 2 trial.
   Cytryn SL, Moy RH, Cowzer D, Shah RH, et al · · 2023 · cited 35× · PMID 37666264 · DOI 10.1016/s1470-2045(23)00358-3
3. Current status and perspectives of esophageal cancer: a comprehensive review.
   Jiang W, Zhang B, Xu J, Xue L, et al · · 2025 · cited 28× · PMID 39723635 · DOI 10.1002/cac2.12645
4. Trial Watch: combination of tyrosine kinase inhibitors (TKIs) and immunotherapy.
   Petrazzuolo A, Maiuri MC, Zitvogel L, Kroemer G, et al · · 2022 · cited 23× · PMID 35655707 · DOI 10.1080/2162402x.2022.2077898
5. Current state of the art: immunotherapy in esophageal cancer and gastroesophageal junction cancer.
   Li N, Sohal D. · · 2023 · cited 22× · PMID 37995002 · DOI 10.1007/s00262-023-03566-5
6. Overcoming physical stromal barriers to cancer immunotherapy.
   Chung SW, Xie Y, Suk JS. · · 2021 · cited 20× · PMID 34351575 · DOI 10.1007/s13346-021-01036-y
7. Immunotherapy in the neoadjuvant treatment of gastrointestinal tumors: is the time ripe?
   Gervaso L, Ciardiello D, Oliveira RA, Borghesani M, et al · · 2024 · cited 12× · PMID 38782539 · DOI 10.1136/jitc-2023-008027
8. Leveraging the synergy between anti-angiogenic therapy and immune checkpoint inhibitors to treat digestive system cancers.
   Xu Q, Shao D. · · 2024 · cited 9× · PMID 39691707 · DOI 10.3389/fimmu.2024.1487610