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Patients With Any Advanced Solid TumorsPhase 1PEMBIBNCT02856425

Trial Of Pembrolizumab And Nintedanib

A Phase 1 study testing Nintedanib and Pembrolizumab in people with Patients With Any Advanced Solid Tumors, run by Gustave Roussy, Cancer Campus, Grand Paris at 5 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Both anti-angiogenesis and anti PD1 immunotherapy have shown beneficial efficacy in solid tumors and in particular in NSCLC. Therefore it is of interest to investigate whether the combination of these two approaches is tolerable. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Patients With Any Advanced Solid Tumors
What is being tested?
Nintedanib and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
196 participants
Where
5 sitesFrance
Study dates
10 Nov 2016to 10 Jan 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18
  • Patients with advanced/metastatic cancer who have progressed after at least one line of standard therapy or are intolerant to standard therapy. Patients must fit into one of the following groups:
  • Colorectal adenocarcinoma (not mismatch repair deficient by either PCR and/or IHC) Gastric or gastroesophageal adenocarcinoma (not mismatch repair deficient by either PCR and/or IHC Patients with advanced or metastatic Urothelial cancer (UC) Patients with advanced Renal Cell cancer (RCC) Patients with advanced Mesothelioma (MPM) Patients with advanced squamous cell carcinoma in Cervical Cancer (CC) Patients with advanced Hepatocellular (HCC) Patients with advanced Thymic Carcinoma (TC) Patients with advanced cancers and high tumor mutational burden (TMB-High) on their circulating tumor DNA (ctDNA) as defined by more than twenty mutations per megabase (≥20Mut/Mb) on FoundationOne Liquid CDx assay. Patients should be without known therapeutic options to provide clinical benefit.
  • ECOG performance status of score 0 or 1
  • Adequate organ function as defined by the following criteria :
  • Proteinuria ≤ Grade 2 NCI CTCAE v4.03
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  • Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min
  • Total bilirubin within normal range (≤ 1.5 x ULN if HCC)
  • AST and ALT ≤ 1.5 x upper limit of normal (ULN); if liver metastases AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN if HCC)
  • Coagulation parameter : International normalized ratio (INR) < 2, prothrombin time (PT) and partial thromboplastin time (PTT) < 50% of deviation of ULN
  • Absolute Neutrophils count (ANC) ≥ 1000 cells/mm^3
  • Platelets ≥100 000 cells/mm^3
  • Hemoglobin ≥ 9.0 g/dL
  • At least one measurable lesion according to RECIST v1.1 (Appendix 4) criteria and modified RECIST for mesothelioma only (Appendix 6) or any other baseline prerequisite for the assessment of the principal judgment criteria.
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment. Both sexually active females and males (and their female partners) patients must agree to use two methods of effective contraception, one of them being a barrier method, or to abstain from sexual activity during the study and for at least 4 months after last study drug administration.
  • Signed and dated written informed consent prior to admission to the study
  • Patient affiliated to a social security regimen or beneficiary of the same

Who cannot join

  • Prior treatment with nintedanib
  • Known hypersensitivity to trial drugs or their excipients, peanut or soya or to contrast media
  • Prior treatment with pembrolizumab or any other anti PD1 or anti-PDL1 agents
  • Concurrent steroid medication (except topical or aerosol steroids). Any steroid medication should have been stopped for more than 7 days prior beginning of therapy.
  • History of autoimmune/immune mediated inflammatory disease, including but not limited to colitis, pneumonitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, systemic lupus erythematous, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, vasculitis, or glomerulonephritis (see Appendix 3). Patients with a history of auto-immune endocrinopathy (hypo/hyper thyroiditis, type 1 diabetes mellitus, …) and who are stable on hormone replacement therapy are eligible for the study. Patients with a history of vitiligo, pelade, cutaneous psoriasis and grade 1-2 Sjogren syndrome are eligible.
  • Chemo-, hormono-, radio- (except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks or 5 half-life times (whatever the shortest) prior to treatment with the trial drugs.
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  • Administration of a live, attenuated vaccine within 4 weeks before registration
  • Treatment with systemic immunosuppressive medications (including but not limited to steroids azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to registration
  • Radiotherapy to the target lesion (unless a progression after radiotherapy has been documented)
  • Persistence of clinically relevant treatment-related toxicity from previous chemotherapy, targeted therapy and/or radiotherapy
  • Active brain metastases or leptomeningeal disease. Clinically asymptomatic brain metastases and clinically asymptomatic leptomeningeal disease are allowed (treatment with steroids prior initiation of the trial is not allowed). Patients with Diffuse Intrinsic Pontine Gliomas, even asymptomatic, are not allowed.
  • Radiographic evidence of cavitary tumors with local invasion of major blood vessels and/or at risk for perforation
  • History of clinically significant hemoptysis within the past 3 months (more than one teaspoon of fresh blood per day)
  • Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial
  • Therapeutic anticoagulation with drugs requiring INR monitoring (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325mg per day)
  • Major injuries and/or surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period
  • History of clinically significant hemorrhagic or thromboembolic event in the past 6 months
  • Known inherited (genetic) predisposition to bleeding or thrombosis (such deficit in protein C/S) or acquired predisposition to thrombosis (such as anti-phospholipid syndromes)
  • History of significant cardiovascular diseases ( i.e. supraventricular tachycardia, uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)
  • Ongoing uncontrolled auto-immune thyroiditis. Ancient thyroiditis currently stable with substitutive therapy should not be excluded from the trial.
  • Other malignancies within the past 5 years other than basal cell skin cancer or carcinoma in situ of the cervix. A history of more than 3 years of local prostate cancer treated by surgery and without PSA elevation since surgery, or local breast carcinoma treated by surgery without relapse are eligible.
  • Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy
  • Known to be human immunodeficiency virus (HIV) positive;
  • Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
  • Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study.
  • Pregnancy or breast feeding,
  • Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
  • Active alcohol or drug abuse
  • Intake of Ganoderma Lucidum mushroom and/or herbal remedies and/or traditional medicines within the past 4 weeks prior to start of study treatment or concomitantly with the trial

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

France5 sites

  • Institut Bergonié

    Bordeaux, 33000

  • Centre Léon Bérard

    Lyon, 69008

  • Hôpital Bichat

    Paris, 75018

  • IUCT--O

    Toulouse, 31059

  • Gustave Roussy

    Villejuif, Val De Marne, 94805

Other trials in France

About this study

Official title: Phase Ib Trial Of Pembrolizumab And Nintedanib

Both anti-angiogenesis and anti PD1 immunotherapy have shown beneficial efficacy in solid tumors and in particular in NSCLC. Therefore it is of interest to investigate whether the combination of these two approaches is tolerable. Moreover, comprehensive pre-clinical and clinical rationale sustain the hypothesis that anti-VEGF could synergize with immunotherapy for the benefit of the patients.

Being tested
Nintedanib, Pembrolizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NintedanibDrug

    Nintedanib oral tablets. An angiokinase inhibitor targeting VEGFR 1-3, FGFR 1-3, and PDGFR α/β as well as RET. Refer to current IB for product details

  • PembrolizumabDrug

    Pembrolizumab, Intravenous. An IgG4 anti-PD-1 blocking monoclonal antibody. Refer to current IB for product details

Study groups in NCT02856425
Study groupRoleWhat they receive
Colorectal adenocarcinoma (not mismatch repair deficient by either PCR and/or IHC)ExperimentalNot described
Receives: Drug: Nintedanib; Drug: Pembrolizumab
Gastric or gastroesophageal adenocarcinoma (not mismatch repair deficient by either PCR and/or IHCExperimentalNot described
Receives: Drug: Nintedanib; Drug: Pembrolizumab
Urothelial cancerExperimentalNot described
Receives: Drug: Nintedanib; Drug: Pembrolizumab
Renal Cell cancer (RCC)ExperimentalNot described
Receives: Drug: Nintedanib; Drug: Pembrolizumab
Mesothelioma (MPM)ExperimentalNot described
Receives: Drug: Nintedanib; Drug: Pembrolizumab
Cervical Cancer (CC)ExperimentalNot described
Receives: Drug: Nintedanib; Drug: Pembrolizumab
Hepatocellular (HCC)ExperimentalNot described
Receives: Drug: Nintedanib; Drug: Pembrolizumab
Thymic Carcinoma (TC)ExperimentalNot described
Receives: Drug: Nintedanib; Drug: Pembrolizumab
Patients with advanced cancers and high tumor mutational burden (TMB-High)ExperimentalHigh tumor mutational burden (TMB-High) on their circulating tumor DNA (ctDNA) as defined by more than twenty mutations per megabase (≥20Mut/Mb) on FoundationOne Liquid CDx assay
Receives: Drug: Nintedanib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD of Nintedanib

    The primary endpoint is to determine the MTD of nintedanib based on the assessment of DLT occurrence during treatment Course 1.

    Measured: Assessed within 24 months after study start

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2016 (estimated)
  2. Study start10 Nov 2016
  3. Primary completion10 Jan 2025
  4. Study completion10 Jan 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
196 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02856425
Sponsor's protocol ID
2015-004511-21
Other IDs
2015/2329, 2015
Acronym
PEMBIB
Status last verified
Jan 2026
First submitted
2 Aug 2016
Last updated
20 Jan 2026
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Baldini C, Danlos FX, Varga A, Texier M, Halse H, Mouraud S, Cassard L, Champiat S, Signolle N, Vuagnat P, Martin-Romano P, Michot JM, Bahleda R, Gazzah A, Boselli L, Bredel D, Grivel J, Mohamed-Djalim C, Escriou G, Grynszpan L, Bigorgne A, Rafie S, Abbassi A, Ribrag V, Postel-Vinay S, Hollebecque A, Susini S, Farhane S, Lacroix L, Parpaleix A, Laghouati S, Zitvogel L, Adam J, Chaput N, Soria JC, Massard C, Marabelle A. Safety, recommended dose, efficacy and immune correlates for nintedanib in combination with pembrolizumab in patients with advanced cancers. J Exp Clin Cancer Res. 2022 Jul 7;41(1):217. doi: 10.1186/s13046-022-02423-0.

    PubMed 35794623

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nintedanib and Pembrolizumab in people with Patients With Any Advanced Solid Tumors, run by Gustave Roussy, Cancer Campus, Grand Paris at 5 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD of Nintedanib (time frame: Assessed within 24 months after study start). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02856425, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026.

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