Platform Trial Assessing Uptake, Safety and Efficacy of Theranostic Agents in Solid Tumors With Active Brain Metastases

This is an international, multicenter, open-label, multicohort, platform design trial comprising the development of theranostic cards, and diagnostic and therapeutic phases. Based on the preliminary analysis, the platform identifies the best strategy for the clinical development of each specific Investigational Medicinal Product (IMP) in the context of solid tumors and active brain metastases. The flexible design of the trial adapts to the specific developmental needs of each IMP. Analysis of each agent will be performed extracting preliminary data from available sources and literature review. The diagnostic phase is comprised of three Stages. The therapeutic phase is comprised of two Stages. Patients enrolled must be ≥18 years of age with solid tumors and active brain metastases (BMs), who have evidence of at least one measurable brain lesion of ≥10 mm on T1-weighted, gadolinium-enhanced magnetic resonance imaging (MRI) according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, life expectancy ≥ 6 weeks, and adequate bone marrow and organ function are mandatory. After treatment discontinuation (EoT), all patients will have a safety visit scheduled 28 days (± 7 days) after the last dose of IMP, in order to follow up toxicities and changes in concomitant medication. Should alternative timelines be necessary based on the IMP, these will be detailed in the corresponding appendix. After the safety visit, all patients treated in the therapeutic phase will enter a post treatment follow-up period during which survival status and subsequent anticancer therapy information will be collected every 3 months (± 7 days) until death, lost to follow-up, elective withdrawal from the study, or the End of Study (EoS), whichever occurs first. This information may be collected by telephone call. Patients who discontinue treatment without evidence of disease progression will be followed every 6 months (± 14 days) for tumor assessments until documented progression, elective withdrawal from the study, the start of new anti-cancer treatment, or study completion or termination. Safety long-term follow-up will be established based on the cohort and the specific IMP as explained in the IMP specific appendix section. The THERANOVA Expert Committee took the decision to test the radiotracer targeting somatostatin receptor 2 (SSTR2) (\[68Ga\]Ga-DOTA-TOC) in the diagnostic phase for patients with Human Epidermal Growth Factor Receptor (HER2)-positive breast cancer and brain metastases as the first cohort. The decision to assess \[68Ga\]Ga-DOTA-TOC in the diagnostic phase for this population reflects the potential of Radioligand therapies (RLTs) to target brain lesions. The current platform Study incorporates essential design components that may be crucial for a comprehensive evaluation of the balance between benefits and risks of \[68Ga\]Ga-DOTA-TOC in patients with solid tumors and BMs. The eligibility criteria are designed to maximize the diagnostic value of \[68Ga\]Ga-DOTA-TOC and minimize its potential associated risks.