NIPU: a randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma

Our plain-English summary of NIPU: a randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma, by V.D. Haakensen, A.K. Nowak, E.B. Ellingsen, et al (Journal of Translational Medicine, 2021).

The study

• Authors: V.D. Haakensen, A.K. Nowak, E.B. Ellingsen, S.J. Farooqi, M.M. Bjaanæs, H. Horndalsveen, T. Mcculloch, O. Grundberg, S.M. Cedres, Å. Helland
• Journal: Journal of Translational Medicine
• Published: 2021;19(1):232
• Type of article: Randomized trial
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour. For patients with inoperable disease, few treatment options are available after first line chemotherapy. The combination of ipilimumab and nivolumab has recently shown increased survival compared to standard chemotherapy, but most patients do not respond and improvements are called for. Telomerase is expressed in mesothelioma cells, but only sparsely in normal tissues and is therefore an attractive target for therapeutic vaccination. Vaccination against telomerase is tolerable and has shown to induce immune responses associated with increased survival in other cancer types. There is a well-founded scientific rationale for the combination of a telomerase vaccine and checkpoint inhibition to improve treatment response in MPM patients.

Methods: NIPU is a randomized, multi-centre, open-label, phase II study comparing the efficacy and safety of nivolumab and ipilimumab with or without telomerase vaccine in patients with inoperable malignant pleural mesothelioma after first-line platinum-based chemotherapy. Participants (n = 118) are randomized 1:1 into two treatment arms. All participants receive treatment with nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks) until disease progression, unacceptable toxicity or for a maximum of 2 years. Patients randomised to the experimental arm receive 8 intradermal injections of UV1 vaccine during the first three months of treatment. Tumour tissue, blood, urine, faeces and imaging will be collected for biomarker analyses and exploration of mechanisms for response and resistance to therapy.

Discussion: Checkpoint inhibition is used for treatment of mesothelioma, but many patients still do not respond. Increasing therapy response to immunotherapy is an important goal. Possible approaches include combination with chemotherapy, radiotherapy, targeted therapy and other immunotherapeutic agents. Predictive biomarkers are necessary to ensure optimal treatment for each patient and to prevent unnecessary side effects. This trial seeks to improve treatment response by combining checkpoint inhibition with a telomerase vaccine and also to explore mechanisms for treatment response and resistance. Knowledge gained in the NIPU study may be transferred to the first line setting and to other cancers with limited benefit from immunotherapy.

Trial Registration: ClinicalTrials.gov: NCT04300244, registered March 8th, 2020, https://clinicaltrials.gov/ct2/show/NCT04300244?term=NIPU&draw=2&rank=1 .

In plain English

This article is a study protocol. It describes a planned clinical trial and reports no results. The NIPU trial is a randomised, multi-centre, open-label phase II study in patients with inoperable malignant pleural mesothelioma that had progressed after first-line platinum-based chemotherapy. The plan was to randomise 118 patients equally to two groups. Both groups were to receive nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or until disease progression or unacceptable toxicity. One group would also receive eight skin injections of UV1, a vaccine directed against telomerase, during the first 13 weeks. The main outcome was to be progression-free survival, judged by blinded, independent central review. Tumour tissue, blood, urine, faeces and PET scans were to be collected to look for markers of response. Recruitment began in June 2020, led by Oslo University Hospital, with centres in Australia, Denmark, Sweden and Spain. The authors noted one challenge: patients given checkpoint inhibitors as first treatment cannot join, so the eligible population will shrink. The trial did not study asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Study protocol for a randomised, multi-centre, open-label phase II (proof of concept) trial. The primary end point is progression-free survival by modified RECIST, assessed by blinded, independent central review. The sample size was planned to yield 69 progression events.
• Who was studied: A planned 118 patients with inoperable malignant pleural mesothelioma progressing after first-line platinum-based chemotherapy, randomised 1:1 (59 per arm). The sponsor is Oslo University Hospital, with recruiting centres in Australia, Denmark, Sweden and Spain. Recruitment started in June 2020 and was expected to finish by May 2022. By March 2021, patients had been included in Norway, Australia and Denmark.
• Exposure: This is a treatment trial, not a study of asbestos exposure. Both arms receive nivolumab 240 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks for up to 2 years. Arm A also receives 8 intradermal injections of the telomerase vaccine UV1 (300 μg) with 75 μg GM-CSF (sargramostim) during the first 13 weeks.
• The authors' conclusion: The authors stated that, because this combination had not previously been studied in mesothelioma, a phase 2 study was warranted before a phase 3 trial. They added that the clinical data may be relevant to first-line treatment in the future.
• Limitations the authors state:
  • Patients treated with checkpoint inhibitors as first-line treatment are not eligible, so once ipilimumab/nivolumab becomes standard first-line treatment, the eligible population will rapidly shrink.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Ipilimumab (Yervoy), Malignant Mesothelioma, Pleural Mesothelioma, Chemotherapy, Mesothelioma, Disease Progression, Biomarker.

Related studies

• Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial — A. Scherpereel, J. Mazieres, et al. (2019)
• Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2 study — L. Calabrò, A. Morra, et al. (2018)
• Switch-maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma (NVALT19): an investigator-initiated, randomised, open-label, phase 2 trial — C.J. de Gooijer, V. van der Noort, et al. (2021)
• Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial — C. Pinto, P.A. Zucali, et al. (2021)
• Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial — M. Maio, A. Scherpereel, et al. (2017)
• Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine — S. Thunold, E. Hernes, et al. (2025)

Browse more research in Journal of Translational Medicine, or return to medical research.