Trial Of Pembrolizumab And Nintedanib

NCT02856425 | Completed Phase 1

• 2 other identifiers: 2015-004511-212015/2329
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 5

Brief 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. Moreover, comprehensive pre-clinical and clinical rationale sustain the hypothesis that anti-VEGF could synergize with immunotherapy for the benefit of the patients.

Conditions

Patients With Any Advanced Solid Tumors

Outcome Measures

Primary Outcomes (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.

  Assessed within 24 months after study start

Study Arms (9)

Colorectal adenocarcinoma (not mismatch repair deficient by either PCR and/or IHC)

EXPERIMENTAL

Drug: Nintedanib; Drug: Pembrolizumab

Gastric or gastroesophageal adenocarcinoma (not mismatch repair deficient by either PCR and/or IHC

EXPERIMENTAL

Drug: Nintedanib; Drug: Pembrolizumab

Urothelial cancer

EXPERIMENTAL

Drug: Nintedanib; Drug: Pembrolizumab

Renal Cell cancer (RCC)

EXPERIMENTAL

Drug: Nintedanib; Drug: Pembrolizumab

Mesothelioma (MPM)

EXPERIMENTAL

Drug: Nintedanib; Drug: Pembrolizumab

Cervical Cancer (CC)

EXPERIMENTAL

Drug: Nintedanib; Drug: Pembrolizumab

Hepatocellular (HCC)

EXPERIMENTAL

Drug: Nintedanib; Drug: Pembrolizumab

Thymic Carcinoma (TC)

EXPERIMENTAL

Drug: Nintedanib; Drug: Pembrolizumab

Patients with advanced cancers and high tumor mutational burden (TMB-High)

EXPERIMENTAL

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

Drug: Nintedanib; Drug: Pembrolizumab

Interventions

Nintedanib DRUG

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

Cervical Cancer (CC); 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; Hepatocellular (HCC); Mesothelioma (MPM); Patients with advanced cancers and high tumor mutational burden (TMB-High); Renal Cell cancer (RCC); Thymic Carcinoma (TC); Urothelial cancer

Pembrolizumab DRUG

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

Cervical Cancer (CC); 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; Hepatocellular (HCC); Mesothelioma (MPM); Patients with advanced cancers and high tumor mutational burden (TMB-High); Renal Cell cancer (RCC); Thymic Carcinoma (TC); Urothelial cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (5)

Gustave Roussy

Villejuif, Val De Marne, 94805, France

Location

Institut Bergonié

Bordeaux, 33000, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hôpital Bichat

Paris, 75018, France

Location

IUCT--O

Toulouse, 31059, France

Location

Related Publications (1)

• 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.

  PMID: 35794623 DERIVED

MeSH Terms

Interventions

nintedanib; pembrolizumab

Study Officials

• Aurélien Marabelle, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2016
• First Posted: August 4, 2016
• Study Start: November 10, 2016
• Primary Completion: January 10, 2025
• Study Completion: January 10, 2026
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)