Neoplasms

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Mesothelioma, Malignant

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Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

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Thoracic Neoplasms

Pleural Neoplasms

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Malignant Mesothelioma

All Drugs and Chemicals

Antineoplastic Agents

Sargramostim

Vaccines

Nivolumab

Ipilimumab

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Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Immunologic Factors

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.

UV1 vaccine + leukine

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

ipilimumab

nivolumab

Åslaug Helland, Prof, MD

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.

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.

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.

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

Nivolumab and Ipilimumab +/- UV1 Vaccination as Second Line Treatment in Patients With Malignant Mesothelioma (the NIPU-study)

Generating TCR repertoire data and comparing differences pre- and post treatment between the two treatment arms

Characterization of TMB pre- and post-treatment by DNA analyses of tumor and normal tissue to identify tumor-specific somatic mutations, and comparing results to clinical outcome data.

By characterizing qualitative and quantitative differences in markers of immune activation within tumor samples pre and post therapy by immunohistochemistry.

By detection of vaccine-specific T cells in PBMC harvested from patients by T cell proliferation assays

The trial will compare DTH measurements With vaccine-specific T-cell response in blood.

Stool samples will be collected and data on microbial gut composition for each patient will be correlated With treatment outcome.

Progression-free survival (PFS) per Modified Response Evaluation Criteria in Solid Tumors (RECIST) as determined by blinded independent central review (BICR) assessed by radiologic assessments

Comparison of response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1 (Modified RECIST), in patients who receive nivolumab and ipilimumab with patients who receive nivolumab and ipilimumab in combination with UV1.

To evaluate changes from baseline in patient-reported outcomes (PROs) in patients who receive nivolumab and ipilimumab compared to patients who receive nivolumab and ipilimumab in combination with UV1.

To determine the safety and tolerability of patients receiving ipilimumab and nivolumab With or without UV1 vaccination by monitoring AEs and study drug discontinuation due to AEs.

tolerability in patients who receive nivolumab and ipilimumab compared to patients who receive nivolumab and ipilimumab in combination with UV1, measured by adverse events (AE) and study drug discontinuations due to AEs.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Nivolumab and Ipilimumab +/- UV1 Vaccination as Second Line Treatment in Patients With Malignant Mesothelioma	NCT04300244	Cancer Cancer, Lung Cancer of Lung Mesothelioma Mesothelioma; L... Mesothelioma; P... Mesotheliomas P...	UV1 vaccine + l... ipilimumab nivolumab	18 Years -	Oslo University Hospital
Nivolumab and Ipilimumab +/- UV1 Vaccination as Second Line Treatment in Patients With Malignant Mesothelioma	NCT04300244	Cancer Cancer, Lung Cancer of Lung Mesothelioma Mesothelioma; L... Mesothelioma; P... Mesotheliomas P...	UV1 vaccine + l... ipilimumab nivolumab	18 Years -	Oslo University Hospital

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