A Study to Explore Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of Novel Therapeutics in Patients With Early Relapsed Metastatic Triple-negative Breast Cancer

Every year, approximately 170.000 women are diagnosed with triple negative breast cancer(TNBC) and about 80‐85% present with a stage II or III tumor making them eligible toneoadjuvant chemotherapy (NACT). Despite the substantial outcome improvements achievedwith neoadjuvant chemotherapy‐based strategies, at least 50‐60% of patients with TNBC donot achieve pCR and are at higher risk of presenting with early disease recurrences.About 40% of patients with no‐pCR experience distant recurrences within 12 months fromthe end of (neo)adjuvant treatments. Overall, 20‐25% of patients with TNBC develop anearly recurrence at Γëñ 12 months from the end of (neo)adjuvant chemotherapy. Neitherstandard chemotherapy options nor approved targeted therapies exist for 35.000‐40.000women/year with TNBC (Γëê1200 women/year in France) that progress during (neo)adjuvanttreatment or within 1 year from its termination. These patients present a "hard‐to‐treat"disease and a disproportionately high rate of morbidity and mortality. Notwithstanding,they are excluded from most current clinical trials that evaluate the efficacy ofinnovative strategies, with immunotherapy or targeting therapies in combination withchemotherapy. The treatment algorithm in 1st line is often based on the use ofplatine‐containing regimens that provide very low response rates (less than 15%), no morethan 2‐3 months of 1st‐line PFS and a median OS of about 9 months. Yet, comprehensivegenomic analyses performed over the past years on patients with residual disease afterneoadjuvant chemotherapy have not introduced concrete findings for guiding drugdevelopment in this setting. Comparisons of initial biopsies with post‐NACT tumor tissuesrevealed a wide range of profound tumor changes acquired under the selective pressure ofNACT that encompass the development of dominant subclones, tumor immune depletion andstem‐cell phenotype enrichment that cannot be addressed with a single treatment strategy.Therefore, it is necessary to explore a broad range of treatment approaches to cover thedifferent patterns involved. The idea is to set a rapidly recruiting phase I‐II trialsallowing to explore new treatment‐strategies in patients with early recurrent and highlyrefractory TNBC have the potential to fulfil this utmost and urgent medical need.