Trial Condition(s):

Solid tumors

A trial to learn whether Regorafenib in combination with Nivolumab can improve tumor responses and how safe it is for participants with solid tumors

Bayer Identifier:

21136 Identifier:


EudraCT Number:


EU CT Number:

Not Available

Recruitment Complete

Trial Purpose

Researchers are looking for a better way to treat people with solid tumors. Before a treatment can be approved for people to take, researchers do clinical trials to better understand its safety and how it works.
In this trial, the researchers want to learn about regorafenib taken together with nivolumab in a small number of participants with different types
of tumors. These include tumors in the head and neck, the esophagus, the pancreas, the brain, and the biliary tract. The biliary tract includes gall bladder and bile ducts.
The trial will include about 200 participants who are at least 18 years old. All of the participants will take 90 mg of regorafenib as a tablet by mouth. The dose of regorafenib can be adjusted up to 120 mg or down to 60 mg by the doctor based on how well a participant tolerates treatment. All of the participants will receive 480 milligrams (mg) of nivolumab through a needle put into a vein (IV infusion).
The participants will take treatments in 4-week periods called cycles. They will take regorafenib once a day for 3 weeks, then stop for 1 week. In each cycle, the participants will receive nivolumab one time. These 4-week cycles will be repeated throughout the trial. The participants can take nivolumab and regorafenib until their cancer gets worse, until they have medical problems, or until they leave the trial. The longest nivolumab can be given is up to 2 years.
During the trial, the doctors will take pictures of the participants’ tumors using CT or MRI and will take blood and urine samples. The doctors will also do physical examinations and check the participants’ heart health using an electrocardiogram (ECG). They will ask questions about how the participants are feeling and if they have any medical problems.

Inclusion Criteria
- Histologically confirmed selected recurrent or metastatic solid tumor types that have progressed after treatment with standard therapies and for which there are no curative intent surgery or chemoradiation.
- Cohort 1: subjects with HNSCC (Head and neck squamous-cell carcinoma) who have not received prior PD-1/PD-L1 inhibitor therapy.
- Cohort 2: subjects with HNSCC who have progressed on or after prior systemic therapy, at least one of which included a PD-1/PD-L1 inhibitor alone or in combination with chemotherapy.
- Cohort 3: subjects with ESCC (Esophageal Squamous Cell Carcinoma) who progressed on or after platinum and/or fluoropyrimidine based regimen.
- Cohort 4: subjects with PDAC (Pancreatic ductal adenocarcinoma) who have progressed on or after gemcitabine or fluoropyrimidine based regimens.
- Cohort 5: subjects with BTC (Biliary tract carcinoma) (intrahepatic or extrahepatic cholangiocarcinoma or gall bladder cancer) who have progressed on gemcitabine or fluoropyrimidine or platinum therapy or a combination of these agents.
- Cohort 6: subjects with Grade IV GBM (Glioblastoma multiforme) or Grade III AA (Anaplastic astrocytoma) (World Health Organization [WHO] criteria) with unequivocal first progression after surgery followed by radiotherapy and temozolomide. 
- Documented HPV (Human papilloma virus) / p16 status for oropharyngeal cancer.
- Capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
- Adult participants of legal maturity (18 years or older).
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1.
- Adequate hematologic and organ function as assessed by the following laboratory tests performed within 7 d before start of study treatment including:
-- Total bilirubin ≤1.5 x the upper limit of normal (ULN). Total bilirubin (≤3 x ULN) is allowed if Gilbert’s syndrome is documented
-- Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN (≤5 x ULN for participants with liver involvement of their cancer)
- Measurable disease by baseline CT or MRI per RECIST 1.1 or RANO.
- Participants must consent to provide recent biopsy/tumor tissue of a primary tumor lesion or from metastases (e.g. liver, lung) for HNSCC (IO treated) for Stage 1 and 2 and in HNSCC (IO naïve) cohort for Stage 2. 
- Anticipated life expectancy greater than 3 months.
- Be able to swallow and absorb oral tablets.
Exclusion Criteria
- Presence of symptomatic central nervous system (CNS) metastases, leptomeningeal metastases or spinal cord compression. Previously-treated lesions should be stable for at least 6 weeks prior to study entry.
- Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. 
- Prior therapy with PD-1/PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, or any form of immunotherapy to treat cancer (except cohort 2). 
- Cohort 2: More than one prior therapy with PD-1/PD-L1 or CTLA-4 inhibitors, or any other form of immunotherapy to treat cancer. 
-- patients with apparent tumor invasion on organs located adjacent to the esophageal disease (e.g., the aorta or respiratory tract).
-- patients who have previously received taxane agents for recurrent/metastatic cancer.  
-- Primary tumors localized to the brainstem or spinal cord.
-- Presence of diffuse leptomeningeal disease or extracranial disease.
-- Participants requiring > 4 mg of dexamethasone or biologic equivalent per day to control symptoms related to brain tumor and cerebral edema within 21 days of starting study treatment.
- Participants who have known dMMR/MSI-H cancers or NTRK (tropomyosin receptor kinase) fusions.
- Prior therapy with regorafenib.
- Systemic anti-cancer treatment within 14 days or less than 5 half-lives (whichever is shorter) of the first dose of study treatment.
- Participants who have permanent discontinuation of PD-1/PD-L1 therapy due to toxicity. 
- Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within 6 months before the start of study treatment. Active pulmonary emboli or deep vein thrombosis that are significant or not adequately controlled on anticoagulation regimen as per investigator’s judgement.
- History of cardiac disorders as defined by:
-- Congestive heart failure ≥ New York Heart Association (NYHA) class 2: 
-- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), myocardial infarction less than 6 months before start of study drug.
-- Uncontrolled cardiac arrhythmias.
- Poorly controlled hypertension, defined as a blood pressure consistently above 140/90 mmHg despite optimal medical management.
- Participants with an active, known or suspected autoimmune disease. 
- History of (non-infectious) pneumonitis that required steroids, current pneumonitis or interstitial lung disease.
- Active infection > NCI-CTCAE Grade 2.
- Positive test (from historical data or tested during screening) for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- Any positive test result for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating presence of virus, e.g. Hepatitis B surface antigen (HBsAg, Australia antigen) positive (except for participants on anti-viral therapy for HBV with a viral load < 100 IU/mL), or Hepatitis C antibody (anti-HCV) positive (except if HCV-ribonucleic acid [RNA] negative).
- Pregnancy or breast feeding.
- Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial or interfere with the participation for the full duration of the trial.
- Participants with a current or past history of interstitial lung disease or pulmonary fibrosis diagnosed based on imaging or clinical findings.

Trial Summary

Enrollment Goal
Trial Dates
Could I receive a placebo?
Accepts Healthy Volunteers

Where to Participate


Sarah Cannon Cancer Center

Nashville, United States, 37203


University of Texas MD Anderson Cancer Center

Houston, United States, 77030


Istituto Oncologico Veneto IRCCS (IOV)

Padova, Italy, 35128


ASST Grande Ospedale Metropolitano Niguarda

Milano, Italy, 20162


UZ Antwerpen

EDEGEM, Belgium, 2650


Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.

Milano, Italy, 20089


AUSL di Bologna

Bologna, Italy, 40139


CHU de Liège

LIEGE, Belgium, 4000


Hôpital Erasme/Erasmus Ziekenhuis

Brussels, Belgium, 1070


Fondazione IRCCS Istituto Neurologico Carlo Besta

Milano, Italy, 20133


Seoul National University Hospital

Seoul, South Korea, 3080


Severance Hospital, Yonsei University Health System

Seoul, South Korea, 3722


Rocky Mountain Cancer Centers / Aurora, CO

Aurora, United States, 80012


City of Hope National Medical Center

Duarte, United States, 91010


Taipei Veterans General Hospital

Taipei, Taiwan, China, 11217


H. Lee Moffitt Cancer Center & Research Institute

Tampa, United States, 33612


Saitama Cancer Center

Kita-Adachigun, Japan, 362-0806


National Cancer Center Hospital

Chuo-ku, Japan, 104-0045


The Cancer Institute Hospital of JFCR

Koto-ku, Japan, 135-8550


Aichi Cancer Center Hospital

Nagoya, Japan, 464-8681


Kobe University Hospital

Kobe, Japan, 650-0017


China Medical University Hospital

Taichung, Taiwan, China, 40447


Chi-Mei Medical Center, Liouyine

Tainan, Taiwan, China


Institut Claudius Regaud - iUCT Oncopole

TOULOUSE CEDEX 9, France, 31059


Institut Bergonié - Unicancer Nouvelle Aquitaine

Bordeaux, France, 33076


Institut Gustave Roussy - Département de Médecine Oncologique

VILLEJUIF CEDEX, France, 94805


Baylor Charles A. Sammons Cancer Center at Dallas

Dallas, United States, 75246


Centre Léon Bérard

lyon, France, 69008


Royal Marsden Hospital (London)

London, United Kingdom, SW3 6JJ


Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 0YN


University Hospitals Coventry and Warwickshire NHS Trust

Coventry, United Kingdom, CV22DX


Royal Marsden NHS Trust (Surrey)

Sutton, United Kingdom, SM2 5PT


Institut de Cancérologie de l'Ouest - Saint Herblain

Saint-Herblain, France, 44800


Hôpital de la Pitié-Salpétrière

PARIS, France, 75651

Trial Design