New drug combo aims to outperform chemo in Tough-to-Treat stomach cancer

NCT ID NCT04879368

Disease control Sponsor: Australasian Gastro-Intestinal Trials Group Source: ClinicalTrials.gov ↗

First seen Jun 26, 2026 · Last updated Jun 27, 2026 · Updated 1 time

Summary

This phase 3 trial tested whether a combination of two drugs, regorafenib and nivolumab, helps people with advanced gastro-oesophageal cancer live longer than standard chemotherapy. The study included 462 adults whose cancer had stopped responding to prior treatments. The goal was to see if this new approach could improve overall survival.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: regorafenib and nivolumab
What this could lead to: If this combination works, it could offer a new treatment option for people with advanced gastro-oesophageal cancer that has stopped responding to standard chemotherapy.
What could go wrong: This is a phase 3 trial, but the results are not yet known. The combination may not improve survival compared to standard chemo, and side effects from both drugs could be significant.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 3

Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.

Participants

462 people

The number who actually took part.

Started

May 2021

Finished

Apr 2025

Lead sponsor

A research network

The lead sponsor is a research network or cooperative group.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Adults (18 years or over) with metastatic or locally recurrent gastro-oesophageal cancer which: 1. has arisen in any primary gastro-oesophageal site (oesophago-gastric junction (GOJ) or stomach); and 2. is of adenocarcinoma or undifferentiated carcinoma histology; and 3. is evaluable according to Response Evaluation Criteria in Solid Tumours (RECIST Version 1.1) by computed tomography (CT) scan performed within 21 days prior to randomisation. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion prior to study enrolment; and 4. has failed or been intolerant to a minimum of 2 lines of prior anti-cancer therapy for recurrent/metastatic disease which must have included at least one platinum agent and one fluoropyrimidine analogue. Note: Neoadjuvant or adjuvant chemotherapy or chemoradiotherapy will be considered as first line treatment where people have relapsed or progressed within 6 months of completing treatment; Radiosensitising chemotherapy given solely for this purpose concurrent with palliative radiation will not be considered as a line of treatment. Ramucirumab monotherapy, or immunotherapy with a checkpoint inhibitor, will be considered a line of treatment. 5. HER2-positive participants must have received trastuzumab 2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix 1). 3. Ability to swallow oral medication. 4. Adequate bone marrow function (Platelets ≥100x109/L; Absolute Neutrophil Count (ANC) ≥1.5x109/L and Haemoglobin ≥ 9.0g/dL). 5. Adequate renal function (Creatinine clearance \>50 ml/min) based on either the Cockcroft-Gault formula (Appendix 2), 24-hour urine or Glomerular Filtration Rate (GFR) scan; and serum creatinine ≤1.5 x Upper Limit of Normal (ULN). 6. Adequate liver function (Serum total bilirubin ≤1.5 x ULN, and INR ≤ 1.5 x ULN, and Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) ≤2.5 x ULN (≤ 5 x ULN for participants with liver metastases)). Participants being treated with an anti-coagulant, such as warfarin or heparin, will be allowed to participate provided that no prior evidence of an underlying abnormality in these parameters exists. 7. Willing and able to comply with all study requirements, including treatment, timing, and/or nature of required assessments and follow-up. 8. Study treatment both planned and able to start within 7 days after randomisation (note: subjects randomised on a Friday should commence treatment no earlier than the following Monday) 9. Signed, written informed consent Exclusion Criteria: 1. Known allergy to the investigational product drug class or excipients in the regorafenib and/or nivolumab 2. Poorly-controlled hypertension (systolic blood pressure \>140mmHg or diastolic pressure\> 90mmHg despite optimal medical management). 3. Participants with known, uncontrolled malabsorption syndromes 4. Any prior anti-VEGF targeted therapy using small molecule VEGF TKIs (e.g. apatinib). Prior anti-VEGF targeted monoclonal antibody therapies (e.g. bevacizumab and ramucirumab) are permitted. 5. Any prior use of more than one immune checkpoint inhibitor 6. Treatment with any previous drug therapy within 2 weeks prior to first dose of study treatment. This includes any investigational therapy. 7. Use of biological response modifiers, such as granulocyte colony stimulating factor (G-CSF), within 3 weeks prior to randomisation. 8. Concurrent treatment with strong CYP3A4 inhibitors or inducers. 9. Palliative radiotherapy, unless more than 14 days have elapsed between completion of radiation and the date of registration, and adverse events resulting from radiation have resolved to \< Grade 2 according to CTCAE V5.0 10. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization 11. Arterial thrombotic or ischaemic events, such as cerebrovascular accident, within 6 months prior to randomization. 12. Venous thrombotic events and pulmonary embolism within 3 months prior to randomization 13. Any haemorrhage or bleeding event ≥ Grade 3 according to CTCAE v5.0 within 4 weeks prior to randomization. 14. Non-healing wound, ulcer, or bone fracture. 15. Interstitial lung disease with ongoing signs and symptoms 16. Clinical hyperthyroidism or hypothyroidism. Note: non-clinically significant abnormal TFTs (abnormal TSH and abnormal T3 and/or abnormal T4) considered to be due to sick euthyroid syndrome is allowed. 17. Persistent proteinuria of ≥ Grade 3 according to CTCAE v5.0 (equivalent to \> 3.5g of protein over 24 hour measured on either a random specimen or 24 hour collection. 18. Uncontrolled metastatic disease to the central nervous system. To be eligible, known CNS metastases should have been treated with surgery and/or radiotherapy and the patient should have been receiving a stable dose of steroids for at least 2 weeks prior to randomization, with no deterioration in neurological symptoms during this time. 19. History of another malignancy within 2 years prior to randomization. Participants with the following are eligible for this study: 1. curatively treated cervical carcinoma in situ, 2. non-melanomatous carcinoma of the skin, 3. superficial bladder tumours (T1a \[Non-invasive tumour\], and Tis \[Carcinoma in situ\]), 4. treated thyroid papillary cancer 20. Any significant active infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated. Participants with known Hepatitis B/C infection will be allowed to participate providing evidence of viral suppression has been documented and the patient remains on appropriate anti-viral therapy. 21. Patients with acute coronary syndrome (including myocardial infarction and unstable angina), and with a history of coronary angioplasty or stent placement performed within 6 months before enrolment 22. Patients with a ≥ grade 3 active infection according to CTCAE version 5.0 23. Patients with concurrent autoimmune disease, or a history of chronic or recurrent autoimmune disease 24. Patients who require systemic corticosteroids (excluding temporary usage for tests, prophylactic administration for allergic reactions, or to alleviate swelling associated with radiotherapy; if used as replacement therapy e.g. ≤ 10 mg prednisolone or dexamethasone ≤ 2 mg per day) or immunosuppressants, or who have received such a therapy \< 14 days prior to randomisation 25. Patients with a seizure disorder who require pharmacotherapy 26. Serious medical or psychiatric condition(s) that might limit the ability of the patient to comply with the protocol. 27. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to randomization. Men must have been surgically sterilized or use a barrier method of contraception.

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Conditions

The condition(s) this trial relates to.

adenocarcinoma carcinoma gastroesophageal adenocarcinoma gastroesophageal cancer Neoplasm Metastasis

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Gastro-oesophageal cancer

Contacts and locations

Locations

Asan Medical Centre

Seoul, South Korea
Austin Health

Melbourne, Victoria, 3084, Australia
Azienda USL-IRCCS Di Reggio Emilia

Reggio Emilia, Italy
Ballarat Oncology and Haematology Services

Wendouree, New South Wales, 3355, Australia
Border Medical Oncology Research Unit

East Albury, New South Wales, 2640, Australia
Caritas Klinikum Saarbrücken St. Theresia

Saarbrücken, Germany
Charité Universitätsmedizin Berlin

Berlin, Germany
China Medical University Hospital (CMUH)

Taichung, Taiwan
Chung-Ang University Hospital

Seoul, South Korea
Chungbuk National University Hospital

Cheongju-si, South Korea
Coffs Harbour Health Campus

Coffs Harbour, New South Wales, 2450, Australia
Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia
Dong-A University Hospital

Busan, South Korea
Evang. Klinikum Bethel Bielefeld

Gütersloh, North Rhine-Westphalia, Germany
Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia
Fred Hutchinson Cancer Research Centre - South Lake Union Clinic

Seattle, Washington, 98109, United States
Gosford Hospital

Gosford, New South Wales, 2250, Australia
Gyeongsang National University Hospital

Jinju, South Korea
Haeundae Paik Hospital

Busan, South Korea
Hallym University Sacred Heart Hospital

Anyang, South Korea
Helios Bad Saarow

Bad Saarow, Germany
Hokkaido University Hospital

Sapporo, Kita, Japan
Hospital Clinico Universitario De Valencia

Valencia, Spain
Hospital Universitario de Navarra

Pamplona, Spain
IRCCS Fondazione Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy
Institut für Klinisch Onkol Forschung am Krankenhaus Nordwest

Frankfurt, Germany
Istituto Nazionale Tumori di Napoli-IRCCS Fondazione G. Pascale

Naples, Italy
Jeonbuk National University Hospital

Jeonju, South Korea
KEM/Evang. Kliniken Essen Mitte gGmbH

Essen, Germany
Kangbuk Samsung Hospital

Seoul, South Korea
Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan
Kliniken der Stadt Köln

Cologne, Germany
Klinikum Bayreuth

Bayreuth, Germany
Klinikum Leverkusen gGmbH

Leverkusen, Germany
Klinikum Ludwigburg

Ludwigsburg, Germany
Klinikum Magdeburg gGmbH

Magdeburg, Germany
Klinikum rechts der Isar der TU München

München, Germany
Korea University Anam Hospital

Seoul, South Korea
Korea University Guro Hospital

Seoul, South Korea
Kyushu Cancer Center

Fukuoka, Japan
Landesklinikum Wiener Neustadt

Wiener Neustadt, Austria
Landeskrankenanstalten-Betriebsgesellschaft-KABEG

Klagenfurt, Austria
Mayo Clinic Arizona

Scottsdale, Arizona, 85054, United States
Medizinische Universitaet Wien

Vienna, Austria
Monash Health

Clayton, Victoria, 3168, Australia
Monument Health Rapid City Hospital

Rapid City, South Dakota, 57701, United States
National Cancer Centre Hospital East

Chiba, Kashiwa, Japan
National Cheng Kung University Hospital

Taipei, Taiwan
National Taiwan University Hospital (NTUH)

Taipei, Taiwan
Newcastle Private Hospital

New Lambton Heights, New South Wales, 2035, Australia
Norddeutsches Studienzentrum für Innovative Onkologie (NIO)

Hamburg, Germany
Ordensklinikum Linz GmbH Barmherzige schwestern

Linz, Austria
Philipps-Universitat Marburg

Marburg, Germany
Port Macquarie Base Hospital

Port Macquarie, New South Wales, 2444, Australia
Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia
Royal Brisbane and Womens Hospital

Herston, Queensland, 4029, Australia
Royal Darwin Hospital

Tiwi, Northern Territory, 0810, Australia
Royal Hobart Hospital

Hobart, Tasmania, 700, Australia
Royal North Shore Private Hospital

Sydney, New South Wales, 2065, Australia
SMG-SNU Boramae Medical Center

Seoul, South Korea
Saitama Cancer Center

Saitama, Japan
San Camillo Forlanini Hospitals

Roma, Italy
Seoul National University Bundang Hospital

Seoul, South Korea
Seoul National University Hospital

Seoul, South Korea
Shikoku Cancer Center

Matsuyama, Japan
Shizuoka Cancer Center

Shizuoka, Japan
Siouxland Regional Cancer Center

Sioux City, Iowa, 51101, United States
Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia
St Elizabeth Healthcare

Edgewood, Kentucky, 41017, United States
St George Hospital

Kogarah, New South Wales, 2217, Australia
St John of God Hospital Subiaco

Subiaco, Western Australia, 6008, Australia
St Vincent's Public Hospital

Darlinghurst, New South Wales, 2010, Australia
Studienzentrum Onkologie Ravensburg

Ravensburg, Germany
Sunshine Coast University Hospital

Sunshine Coast, Queensland, 4560, Australia
Taipei Veterans General Hospital (TPVGH)

Taipei, Taiwan
The Catholic University of Korea - Seoul St. Mary's Hospital

Seoul, South Korea
The Catholic University of Korea - Yeouido St. Mary's Hospital

Seoul, South Korea
The Queen Elizabeth Hospital

Adelaide, South Australia, 5011, Australia
The Townsville Hospital

Douglas, Queensland, 4814, Australia
The Tweed Hospital

Tweed Heads, New South Wales, 2485, Australia
USC Norris

Los Angeles, California, 90001, United States
Universita Cattolica del Sacro Cuore, University Hospital Gemelli

Roma, Italy
Universitae degli studi della Campania "Luigi Vanvitelli"

Naples, Italy
Universitätsklinikum Bonn

Bonn, Germany
Universitätsklinikum Greifswald

Greifswald, Germany
Universitätsklinikum Heidelberg

Heidelberg, Germany
Universitätsklinikum Jena

Jena, Germany
Universitätsklinikum Leipzig

Leipzig, Germany
Universitätsklinikum Mainz

Mainz, Germany
Universitätsklinikum Ulm

Ulm, Germany
Vall d'Hebron University Hospital

Barcelona, Spain
Westmead Hospital

Westmead, New South Wales, 2145, Australia
Yonsei University Health System - Gangnam Severance Hospital

Seoul, South Korea
Yonsei University Health System - Severance Hospital

Seoul, South Korea