Clinical Trials /

Evaluation of UCPVax Plus Nivolumab as Second Line Therapy in Advanced Non Small Cell Lung Cancer

NCT04263051

Description:

Lung cancer is the most commonly diagnosed malignancy and the leading cause of cancer-related mortality both in men and women worldwide. The past few years have demonstrated great progress in the field of tumor immunotherapy through agents that address mechanisms of immune escape notably, so called immune checkpoint inhibitors (ICB). Indeed, ICB have emerged as a fatal weapon in the anticancer treatment arsenal. Anti-PD-1 and anti-PD-L1 antibodies have shown promising results in several cancers including Non-small Cell Lung Cancer (NSCLC) patients. Although such ICB extend patient's survival compared with conventional systemic therapies, they fail to control cancer progression in a significant proportion of patients which can reach up to 50-60% in NSCLC. Recent literature highlights a range of factors involved in the heterogeneous responses and failures to ICB therapies. The challenge is how can ICB treatment efficacy be extended to majority patients? To respond to this question, to increase the success of immunotherapy, immuno-oncology community develops combinations approaches. The aim of these project is to evaluate the efficacy of Nivolumab plus a novel CD4Th1 inducer anti-cancer vaccine in NSCLC patients. Nivolumab (NIVO), which is an anti-PD-1 antibody, has shown promising results in 2nd line treatment for advanced NSCLC. UCPVax is a therapeutic anti-cancer vaccine based on the telomerase-derived helper peptides designed to induce strong TH1 CD4 T cell responses in cancer patients (NCT02818426).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Evaluation of UCPVax Plus Nivolumab as Second Line Therapy in Advanced Non Small Cell Lung Cancer
  • Official Title: Evaluation of UCPVax Plus Nivolumab as Second Line Therapy in Advanced Non Small Cell Lung : a Randomized Non Comparative Phase II Trial

Clinical Trial IDs

  • ORG STUDY ID: P/2019/451
  • NCT ID: NCT04263051

Conditions

  • Advanced Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
UCPVax + NivolumabUCPVax + Nivolumab
standard chemotherapyStandard second line chemotherapy

Purpose

Lung cancer is the most commonly diagnosed malignancy and the leading cause of cancer-related mortality both in men and women worldwide. The past few years have demonstrated great progress in the field of tumor immunotherapy through agents that address mechanisms of immune escape notably, so called immune checkpoint inhibitors (ICB). Indeed, ICB have emerged as a fatal weapon in the anticancer treatment arsenal. Anti-PD-1 and anti-PD-L1 antibodies have shown promising results in several cancers including Non-small Cell Lung Cancer (NSCLC) patients. Although such ICB extend patient's survival compared with conventional systemic therapies, they fail to control cancer progression in a significant proportion of patients which can reach up to 50-60% in NSCLC. Recent literature highlights a range of factors involved in the heterogeneous responses and failures to ICB therapies. The challenge is how can ICB treatment efficacy be extended to majority patients? To respond to this question, to increase the success of immunotherapy, immuno-oncology community develops combinations approaches. The aim of these project is to evaluate the efficacy of Nivolumab plus a novel CD4Th1 inducer anti-cancer vaccine in NSCLC patients. Nivolumab (NIVO), which is an anti-PD-1 antibody, has shown promising results in 2nd line treatment for advanced NSCLC. UCPVax is a therapeutic anti-cancer vaccine based on the telomerase-derived helper peptides designed to induce strong TH1 CD4 T cell responses in cancer patients (NCT02818426).

Trial Arms

NameTypeDescriptionInterventions
UCPVax + NivolumabExperimentalUCPVax vaccine (1 mg) Nivolumab (240 mg)
  • UCPVax + Nivolumab
Standard second line chemotherapyOtherStandard second line chemotherapy at the choice of the investigator. This arm will permit to assess the good calibration of the hypothesis on the experimental arm.
  • standard chemotherapy

Eligibility Criteria

        Inclusion Criteria:

          -  Signed informed consent

          -  Age ≥ 18 years

          -  Histologically or cytologically confirmed NSCLC (adenocarcinoma, squamous cell
             carcinoma, large cell carcinoma, undifferentiated carcinoma or other)

          -  Advanced NSCLC cancer patient previously treated with a first line of combo
             chemotherapy plus anti-PD-1 or chemotherapy plus anti-PDL-1 combination

          -  Measurable disease defined according to iRECIST v1.1 guidelines

          -  Patients must have a mandatory treatment-free interval of at least 21 days following
             previous systemic anti-cancer treatments

          -  Patients who have received previous systemic anticancer treatment and/or radiotherapy
             should have recovered from any treatment related toxicity, to a level of ≤ grade 1
             with the exception of Grade 2 alopecia

          -  Performance status 0 or 1 on the ECOG scale

          -  Females must be using highly effective contraceptive measures and have a negative
             pregnancy test prior to the start of dosing if of childbearing potential, or must have
             evidence of non-childbearing potential. Females of childbearing potential should use
             reliable methods of contraception from the time of the screening until 5 months after
             discontinuing study treatment. Male patients with a female partner of childbearing
             potential should be willing to use barrier contraception during the study and for 7
             months following discontinuation of study drug. Patients should refrain from donating
             sperm from the start of dosing until 7 months after discontinuing study treatment.

          -  Registration in a national health care system.

          -  Ability to comply with the study protocol, in the Investigator's judgment

        Exclusion Criteria:

          -  Diagnosis of additional malignancy within 2 years prior to the inclusion with the
             exception of curatively treated basal cell carcinoma of the skin and/or curatively
             resected in situ cervical or breast cancer

          -  Patient with any medical or psychiatric condition or disease, which would make the
             patient inappropriate for entry into this study

          -  Participation in a clinical study with an investigational product within 4 weeks prior
             to the start of the study treatment

          -  Patient under guardianship, curatorship or under the protection of justice

          -  Uncontrolled tumor-related pain

          -  Uncontrolled pleural effusion, pericardial effusion, ascites or symptomatic fistula

          -  Known active central nervous system metastases and/or carcinomatous meningitis

          -  Uncontrolled brain metastases

          -  Presence of EGFR mutation, ALK or ROS1 translocation

          -  Inadequate organ functions: known cardiac failure of unstable coronaropathy,
             respiratory failure, or uncontrolled infection or another life-risk condition

          -  Active or chronic hepatitis B or C and/or HIV positive or a known history of active
             Tuberculosis bacillus

          -  Any immunosuppressive therapy (i.e. corticosteroids >10mg of hydrocortisone or
             equivalent dose) within 14 days before the planned start of study therapy

          -  Active autoimmune disease that has required a systemic treatment in past 2 years (i.e.
             corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine,
             insulin) is allowed

          -  Active or history of autoimmune disease or immune deficiency

          -  Prior allogeneic bone marrow transplantation or prior solid organ transplantation

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Known hypersensitivity or allergy to Chinese hamster ovary cell products or any
             component of Nivolumab formulation

          -  History of idiopathic or secondary pulmonary fibrosis or evidence of active
             pneumonitis requiring a systemic treatment with 28 days before the planned start of
             study therapy

          -  Major surgical procedure other than for diagnosis within 4 weeks prior to initiation
             of study treatment, or anticipation of need for a major surgical procedure during the
             course of the study

          -  Severe infection within 4 weeks prior to initiation of study treatment, including, but
             not limited to, hospitalization for complications of infection, bacteremia, or severe
             pneumonia

          -  Treatment with therapeutic oral or IV antibiotics within 4 weeks prior to initiation
             of study treatment

          -  Receipt of a live, attenuated vaccine within 4 weeks prior to the initiation of
             treatment or anticipation that such a live, attenuated vaccine will be required during
             the study

          -  Patients requiring oxygen therapy

          -  Patients with LEVF <40%

          -  Preexistent peripheral neuropathy or impaired audition,

          -  Inadequate hematology, hepatic, renal functions or others inadequate laboratory values
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:6 months Progression-Free Survival (PFS) rate
Time Frame:6 months after the date of initiation of treatment (1st day of 1st cycle of chemotherapy)
Safety Issue:
Description:PFS is defined by the duration from the date of initiation of the treatment to the disease progression (RECIST) or death from any cause whichever occurs first, censoring cases without progression at the date of last disease assessment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Centre Hospitalier Universitaire de Besancon

Last Updated

February 17, 2020