Phase 1 including first-in-human clinical trials to test biomarker-guided medicines or multi-modal treatment interventions for patients with rare or very rare cancers or cancer subtypes

Expected Outcome:

Proposals under this topic should aim to deliver results that are directed and tailored towards, and contribute to all of the following expected outcomes:

• Patients with rare or very rare cancers or cancer subtypes have access to tailored, promising biomarker-guided medicines or multi-modal treatment interventions via participation in subsequent clinical trials or national or regional compassionate use programmes by health authorities;
• Researchers, physicians, innovators^[1], startup, spin-off and spin-out companies, SMEs, charities or foundations and other professionals from different disciplines and sectors have access to innovative technology, medical devices or promising biomarker-guided medicines for further validation or commercialisation;
• National healthcare providers, policymakers and authorities in European regions, EU Member States and Associated Countries have early safety and efficacy evidence to support further testing of affordable biomarker-guided medicines or multi-modal treatment interventions that benefit patients with rare or very rare cancers in their healthcare systems;

Scope:

Patients with rare and very rare^[2] cancers across EU Member States and Associated Countries often present with advanced disease due to late diagnosis and have access to few treatment options. Hence, these patients typically have a lower 5-year overall survival than those with more common cancers and face challenges with timely access to a small number of appropriate phase 1 clinical trials, despite good disease control rates^[3], to validate biomarker-guided medicines or multi-modal treatment interventions targeting their disease and adapted to an increasingly precision oncology healthcare landscape.

Proposals should address all the following:

• When still relevant and required, finalise the preclinical validation of promising^[4] biomarker-guided drugs^[5], for rare or very rare cancer indications through in vivo and/or ex vivo and/or in silico research models. Drug repurposing should be considered^[6]. Data should be disaggregated by tumour biology, sex, gender, age and other relevant variables, such as by measures of socio-economic status or ethnicity;
• Validate early safety and efficacy of innovative medicines or as part of multi-modal treatment interventions in phase 1, including in first-in-human, multi-centre clinical trials, considering new trial designs^[7], for and with patients with rare or very rare cancers and their caregivers/families;
• The primary and secondary endpoints of the clinical trial(s) should support safety, efficacy and patient-reported outcomes. Such endpoints should be defined together with patients and their caregivers through research that stimulates social innovation and supports end-user engagement using participative research models.
• All datasets produced should be described with metadata records in the EU dataset catalogue of the European Health Data Space, while all tools and models should take advantage of current European research infrastructures, should follow the principles of open science and made available through the future UNCAN.eu platform;
• Applicants should include proof of advice from regulators on the design of the clinical trial(s), include an appropriate mix of stakeholders from various disciplines, and regional as well as national health authorities, and provide details of the clinical study(ies) in the dedicated annex using the template provided in the submission system;

Successful proposals will be asked to join the 'Diagnosis and treatment” cluster for the EU Cancer Mission^[8] and should include a budget for networking, attendance at meetings, and joint activities^[9]. The Commission will facilitate coordination of these activities.

The successful proposals are expected to build on resources made available by the Knowledge Centre on Cancer (KCC)^[10] to foster EU alignment and coordination.

[1] Innovators turn research results into new and better services and products, to remain competitive in a global marketplace and to improve the quality of life of Europe’s citizens.

[2] ~24% of all cancers are rare. For definition and incidence of rare cancers see ESMO and RARECARE

[3] Profile and outcome of cancer patients enrolled in contemporary phase I trials - ScienceDirect

[4] for example promising efficacy, pharmacokinetics and pharmacodynamics data

[5] any relevant molecular target, biomarker, therapeutic strategy or technology

[6] Potential applicants may want to consider ongoing EU-funded efforts like REMEDI4ALL and/or REPO4EU.

[7] decentralised clinical trials, basket trials, umbrella trials, roll-over/extension trials, adaptive trials

[8] in order to address the objectives of the EU Cancer Mission, participants will collaborate in project clusters to leverage EU-funding, increase networking across sectors and disciplines, and establish a portfolio of EU Cancer Mission R&I and policy actions.

[9] Examples of those activities are research or research capacity, organising joint workshops, establishing best practices, joint communication or citizen engagement activities with projects funded under other clusters and pillars of Horizon Europe, or other EU programmes, as appropriate. Proposals are not required to include details of these activities, as they will be defined during the grant agreement preparation and during the life of the project.

[10] Hosted by the European Commission's Joint Research Centre (JRC). Especially through the ’European Guidelines and Quality Assurance Schemes for Breast, Colorectal and Cervical Cancer Screening and Diagnosis‘, and the ’European Cancer Information System (ECIS)’ and the ’European Cancer Inequalities Registry (ECIR), see https://knowledge4policy.ec.europa.eu/cancer_en.