Cervical cancer (CxCa) is caused by high risk types of the human papillomavirus (a.o. HPV16). Prophylactic HPV vaccination is not the standard of care in all European countries, and where approved it is not sufficiently adopted. Once infected, these vaccines no longer prevent premalignant lesions and CxCa, which can only be treated with surgery or radio-chemotherapy. However, this is not effective in recurrent/advanced CxCa. In underdeveloped countries, CxCa is often detected when it is too late for curative treatment. With an estimated global incidence of 500.000 new cases of CxCa and 274.000 deaths per year, the need for an effective therapy is extremely high. Targeted immunotherapy is an effective approach to induce a tumour-directed immune response. Previously, members of the IMMUNISA consortium have formulated ISA101, a cancer vaccine consisting of overlapping synthetic long peptides covering all epitopes of the HPV16 oncogenic proteins. ISA101 has shown promising Phase 1 clinical trial results in patients with advanced CxCa where it works synergistically with chemotherapy. IMMUNISA now proposes the multi-centre randomised Phase 2 CervISA-2 trial; a careful assessment of the efficacy of the proprietary ISA101b therapeutic vaccine in combination with chemotherapy for the treatment of CxCa, measured by a prolonged progression free survival. A multidisciplinary collaboration between leading clinical EU sites specialised in CxCa, a partner providing strategic and operational regulatory service and a cutting-edge biotech SME will enable the optimal implementation of the CervISA-2 trial, exploitation activities and overall project dissemination. This is pivotal to catapult further development of ISA101b as a commercial vaccine and push it towards clinical implementation as fast as possible. For ISA101b, IMMUNISA will provide, 1) clinical data on the efficacy, 2) a solid exploitation strategy and 3) the regulatory framework for efficient translation to clinical use.

Asbestos is one of the major occupational carcinogens. The European Union has an extensive history of protecting workers and consumers against asbestos and even adopted a resolution 2012/2065(INI) ‘on asbestos related occupational health threats and prospects for abolishing all existing asbestos’ last year. Although asbestos is banned, it is still massively present in the built environment. Millions of workers & consumers in the EU were, and still are, for many years exposed to asbestos fibres, despite all measures. Inhalation of even very low quantities of asbestos fibres tremendously increases the risk of developing Malignant Mesothelioma (MM). The IARC reported 8.100 MM deaths in 2010 in the EU. Despite all EU actions, MM incidence is still increasing. MM is a highly fatal disease with a poor median survival time from first signs of illness to death around 12 months despite aggressive treatments. To date there is no curative therapy for MM. MM is considered as an extremely therapy-resistant disease. Chemotherapy consisting of a combination of pemetrexed and cisplatin is considered standard of care with a median survival increase of 3 months (9-12 months). The department of pulmonary diseases of the Erasmus MC, Rotterdam, The Netherlands, in collaboration with international partners, have developed a promising personalised immunotherapy for MM with very limited adverse effects. The first clinical results show a considerably prolonged average survival with limited adverse events (24 months, twice as long). The EMA and the FDA granted this therapy Orphan Designation: autologous dendritic cells pulsed with allogeneic tumour cell lysate for the treatment of malignant mesothelioma (EU: 16 January 2014 - EU/3/13/1229; FDA – US: 06 May 2014). The objective for the project is to deliver the scientific & registration package for market approval by the EMA of a novel immuno therapeutic approach to treat MM. This includes the execution of a phase II/III clinical trial.

TIGER delivers proof of principle (PoP) in humans for a novel best-in-class therapeutic mRNA cancer vaccine platform optimized for intravenous (IV) administration, with the aim to show clinical benefit. The antigens used for the PoP consists of mRNAs encoding the proteins E6 and E7 of Human Papilloma Virus strain 16 (HPV16), and TriMix mRNAs that act as adjuvant to stimulate dendritic cells to start strong T cell responses. The mRNAs will be formulated in a novel patented lipid nanoparticle shielding the mRNA, and delivering it to immunoactive antigen presenting cells, vastly enhancing T-cell response. Safety and potent efficacy of our IV mRNA product have been demonstrated in rodent experiments. Furthermore, preclinical to clinical translation has been shown for our TriMix based vaccines using different delivery strategies. Based on the preclinical and prior clinical data, our platform has the potential to cure cancer patients. The PoP study will be in patients with recurrent HPV16 positive cancer, which is categorised as a non-communicable disease by the WHO, without and with a PD-1 checkpoint inhibitor. Safety, immunogenicity and clinical benefit will be key endpoints of the study. Biomarker and PROM research will allow future informed therapeutic and care decisions by both patient and care team. Recruitment and stratification plans will be in place. Interactions with regulatory, reimbursement and ethical authorities together with patients and carers will help laying out the route to the patient not only for our product but also for all other mRNA cancer vaccines. The project encompasses essential elements for preparing therapy validation in later stage clinical studies, while addressing patient needs, values and choices. Upscaling of GMP-production for IV mRNA vaccines will enable further clinical studies. Once validated, our platform will be easily translatable to a wide range of cancers using other tumour antigens, be they TSA, TAA or neoantigens.

Challenge: many patients with advanced cancer in the final phase of life leave the hospital without continuity of information, and certainty about further treatment and care provision. Often, communication between healthcare providers in different settings is suboptimal and this leads to poor continuity and coordination of care, negatively impacting the quality of life and increasing preventable hospital admissions. Solution: the PAL-CYCLES programme: a transitional palliative care programme for patients with advanced cancer, adaptable to local cultures and healthcare systems. The programme contains an intervention aiming for a smooth transition from hospital care to community care, consisting of five cornerstone components: (1) identification of a patient with palliative and supportive care needs in collaboration with the oncologist and the hospital palliative care team; (2) compassionate communication towards the patient and their family; (3) a collaborative multidimensional care plan and follow-up in the home care setting; (4) periodic evaluation of the care plan with patients and relatives; (5) identification of the terminal phase (if there) based on the periodic evaluations, with appropriate intensification of care and end-of-life talks depending on local possibilities and habits, including consultation with patient and families about ethically and legally sensitive issues. Plan: we intend to develop, adapt, implement, and evaluate the PAL-CYCLES programme in seven European countries using a stepped wedge randomized controlled trial design. Patient, relatives, and health care provider experiences, as well as ethical and equity issues will be addressed with qualitative methods. Impact: the PAL-CYCLES programme will facilitate patient-centred communication and continuity of palliative cancer care in the community care setting, reducing unplanned hospital admissions and improving quality of life for patients with advanced cancer at the end of life.

The standard medical-and-surgical treatment of ovarian carcinoma patients relies on a systemic chemotherapy (carboplatin-paclitaxel), a tumor debulking surgery meant to be complete (no post-operative residual lesion), and a subsequent maintenance treatment with modern targeted agents. Recent studies identified a patient population (~14,000 patients / year in Europe), whose prognostic is poor (5 year-overall survival (OS) <20%) due to a refractory cancer, characterized by a poor chemosensitivity (assessable online with the numeric CA-125 KELIMTM score <1.0), and by a disease found non-resectable disease after 3-4 cycles of chemotherapy. In these patients, there is a high uncertainty about the best treatment adjustments to apply. SALVOVAR is a European project led by HCL, meant 1) to raise the physician awareness, and propose practical and affordable diagnostic tools for identifying these patients, and 2) to assess the utility (OS benefit), acceptability (quality-of-life; patient perception) and affordability (cost-effectiveness, including country coverage policies) of solutions based on adjustments of their medical-and-surgical treatment. These solutions implementable in routine may improve their prognosis, according to recent literature data. The project will be based on a large pragmatic randomized phase III trial, sponsored by ARCAGY-GINECO group, and activated in 6 countries (ENGOT network; ~100 recruiting centers), with the objective of demonstrating an OS benefit with the chemotherapy densification (weekly carboplatine-paclitaxel dose-dense regimen) compared to the continuation of the standard 3-weekly regimen. Total 685 patients treated with the standard neo-adjuvant chemotherapy will be pre-screened to randomize 240 patients. Dissemination, and communication will be carried-on to ensure the quality of the project, and inform the stakeholders, patients, public, health authorities/ payers of the project outcomes, mean to change the practices. This action is part of the Cancer Mission cluster of projects on ‘Diagnosis and treatment’.