Nivolumab and Ipilimumab +/- UV1 Vaccination as Second Line Treatment in Patients With Malignant Mesothelioma

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

118 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-04

Study Completion Date

2027-03-15

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The objective of the study is to induce a meaningful progression-free survival benefit in patients with Malign Pleural Mesothelioma (MPM) after progression on first line standard platinum doublet chemotherapy, by treating with nivolumab and ipilimumab with or without UV1 vaccine.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Ipilimumab and Nivolumab in the Treatment of Malignant Pleural Mesothelioma

NCT03048474

Malignant Pleural Mesothelioma

COMPLETED PHASE2

Ipilimumab and Nivolumab in Patients With Anti-PD-1-axis Therapy-resistant Advanced Non-small Cell Lung Cancer.

NCT03262779

Carcinoma, Non-Small-Cell Lung

COMPLETED PHASE2

Long-term Outcomes Among Patients With Programmed Death-ligand 1 <1% Metastatic Non-small Cell Lung Cancer Treated With First-line Nivolumab + Ipilimumab + 2 Cycles of Chemotherapy

NCT07024862

Metastatic Non-small Cell Lung Cancer

ACTIVE_NOT_RECRUITING

Evaluate the Mediators of Sensitivity and Resistance to Nivolumab Plus Ipilimumab in Patients With Advanced NSCLCs

NCT02350764

Advanced Stage Non-small Cell Lung Cancer

COMPLETED PHASE2

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

NCT04263051

Advanced Non-small Cell Lung Cancer

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Several studies have investigated the use of checkpoint inhibition in Malign Pleural Mesothelioma (MPM). Most of them are small studies investigating the efficacy of single-agent immunotherapy in few patients. Given that the combination of anti-PD-1 or anti-PD-L1 therapy with CTLA-4 has been shown in other cancers to enhance treatment effect, combined checkpoint inhibitor treatment has also been investigated in patients with MPM. Although these results are encouraging, the response rates seen are moderate compared to what has been documented for the combination of checkpoint inhibitors in other cancer indications. An approach to further enhance the PFS and response rate in MPM may be to use a vaccine aiming to activate an immune response directed against tumor-related antigens, and to combine the vaccine with checkpoint inhibitors. The proposed study will evaluate the use of the therapeutic cancer vaccine UV1 in combination with nivolumab and ipilimumab after progression on standard first-line chemotherapy in patients with malignant pleural mesothelioma.

The objective of the study is to induce a meaningful progression-free survival benefit in patients with MPM after progression on first line standard platinum doublet chemotherapy, by treating with nivolumab and ipilimumab with or without UV1.

The primary end-point (PFS) is expected to be analyzed in 2023.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cancer Cancer, Lung Cancer of Lung Mesothelioma Mesothelioma; Lung Mesothelioma; Pleura Mesotheliomas Pleural

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

randomized, multi-center, open-label, proof of concept study comparing the efficacy and safety of nivolumab and ipilimumab with or without UV1 in patients with inoperable malignant pleural mesothelioma after first-line platinum-based chemotherapy.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Open label

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm A

Ipilimumab and nivolumab + UV1

Group Type EXPERIMENTAL

UV1 vaccine + leukine

Intervention Type BIOLOGICAL

The mode of action of UV1 is to activate the immune system to induce T cells directed against telomerase (hTERT). UV1 vaccination amplifies the pool of hTERT specific tumor-reactive T cells from the naive repertoire and has the potential to increase the breadth and diversity of the tumor-reactive T cell response (epitope spreading). Vaccination with UV1 can thus provide the basis for increased efficacy of checkpoint inhibition therapy, by augmenting the pool of tumor specific T cells in patients with limited or insufficient numbers of T cell clones spontaneously primed by tumor antigens. Reciprocally, the efficacy of UV1 vaccination may be enhanced in combination with checkpoint inhibitors, since the clonal expansion and effector activity of UV1 induced T cells will otherwise be restricted by intrinsic immune regulatory and tumor induced suppressor mechanisms.

ipilimumab

Intervention Type BIOLOGICAL

The responses to ipilimumab and nivolumab combination therapy seen in MPM is encouraging.

nivolumab

Intervention Type BIOLOGICAL

The responses to ipilimumab and nivolumab combination therapy seen in MPM is encouraging.

Arm B

Ipilimumab and nivolumab

Group Type ACTIVE_COMPARATOR

ipilimumab

Intervention Type BIOLOGICAL

The responses to ipilimumab and nivolumab combination therapy seen in MPM is encouraging.

nivolumab

Intervention Type BIOLOGICAL

The responses to ipilimumab and nivolumab combination therapy seen in MPM is encouraging.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

UV1 vaccine + leukine

The mode of action of UV1 is to activate the immune system to induce T cells directed against telomerase (hTERT). UV1 vaccination amplifies the pool of hTERT specific tumor-reactive T cells from the naive repertoire and has the potential to increase the breadth and diversity of the tumor-reactive T cell response (epitope spreading). Vaccination with UV1 can thus provide the basis for increased efficacy of checkpoint inhibition therapy, by augmenting the pool of tumor specific T cells in patients with limited or insufficient numbers of T cell clones spontaneously primed by tumor antigens. Reciprocally, the efficacy of UV1 vaccination may be enhanced in combination with checkpoint inhibitors, since the clonal expansion and effector activity of UV1 induced T cells will otherwise be restricted by intrinsic immune regulatory and tumor induced suppressor mechanisms.

Intervention Type BIOLOGICAL

ipilimumab

The responses to ipilimumab and nivolumab combination therapy seen in MPM is encouraging.

Intervention Type BIOLOGICAL

nivolumab

The responses to ipilimumab and nivolumab combination therapy seen in MPM is encouraging.

Intervention Type BIOLOGICAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Yervoy Opdivo

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Histologically and/or cytologically confirmed malignant pleural mesothelioma.
* Unresectable disease
* Measurable disease, defined as at least 1 lesion (measurable) that can be accurately assessed at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for repeated assessment (modified RECIST).
* Available unstained archived tumor tissue sample in sufficient quantity to allow for analyses. At least fifteen unstained slides or a tumor block (preferred). NOTE: A fine needle aspiration sample is not sufficient to make the patient eligible for enrollment. Given the complexity of mesothelioma pathological diagnosis , it is expected that they will have a core needle biopsy or surgical tumor biopsy as part of their initial diagnostic work up.
* Age ≥ 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
* Willing to provide archived tumor tissue and blood samples for research.
* Adequate organ function as defined below

1. Haemoglobin ≥ 9.0 g/dL
2. Absolute neutrophil count (ANC) 1.5 (or 1.0) x (\> 1500 per mm3)
3. Platelet count ≥100 (or 75) x 109/L (\>75,000 per mm3)
4. Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).
5. AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
6. Measured creatinine clearance (CL)

1. \>40 mL/min
2. Calculated creatinine CL\>40 mL/min (Cockcroft-Gault formula)
3. 24-hour urinecollection for determination of CL
* Males: Creatinine CL (mL/min) =Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
* Females:Creatinine CL (mL/min)=Weight (kg) x (140 - Age)x0.85 72 x serum creatinine (mg/dL)
* Previously treated with at least one line of platinum -pemetrexed

Exclusion Criteria

* Disease suitable for curative surgery
* Previous treatment with a PD-1 or PD-L1 inhibitor, including nivolumab or any other agent targeting immune checkpoints.
* Non-pleural mesothelioma e.g. mesothelioma arising in peritoneum, tunica vaginalis or any serosal surface other than the pleura.
* Active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ.
* Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids (prednisone \>10 mg or equivalent). Surgery, radiation and/or corticosteroids (any dose \>10 mg prednisone equivalent) must have been completed ≥ 2 weeks prior to registration.
* Uncontrolled seizures.
* Current or prior use of immunosuppressive medication within 28 days before the first dose of nivolumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Standard steroid premedication given prior to chemotherapy or as prophylaxis for imaging contrast allergy should not be counted for this criterion.
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome) within the past 2 years. Subjects with vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic treatment (within the past 3 years) are not excluded.
* History of primary immunodeficiency.
* History of allogeneic organ transplant.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
* Active infection including tuberculosis (clinical evaluation including: physical examination findings, radiographic findings, positive PPD test, etc.), hepatitis B (known positive HBV surface antigen \[HBsAg\] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies as defined by a positive ELISA test). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. HIV testing is not required in the absence of clinical suspicion.
* Known history of leptomeningeal carcinomatosis.
* Pregnant or lactating women
* Live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving nivolumab.
* Any condition that, in the opinion of the investigator, would interfere with the evaluation of study treatment or interpretation of patient safety or study results.
* History of allergy or hypersensitivity to any of the active substances or excipients in the study drug.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No