St Gilles Les Hauts, France

First-line Immunotherapy-based Standard of Care and Local Ablative Treatments for Oligometastatic Non-small Cell Lung Cancer Patients.

Prospective Analysis of Circulating Nucleosomes in Patients Receiving a First Line Treatment for a Non-Hodgkin Lymphoma

Safety and Tolerability of IPH4502 in Patients With Advanced Solid Tumors

This is a first-in-human, open-label, multicenter, single-arm Phase 1 study, with a part 1 dose escalation guided by a Bayesian optimal interval design with backfilling (BOIN-BF), followed by a part 2 dose optimization in up to 2 selected indications. This study is to measure the safety, tolerability, pharmacokinetics, and preliminary efficacy of escalating doses of IPH4502 in patients with advanced solid tumors that are known to express Nectin-4.

Validation of KELIM as a Predictive/Prognostic Factor for Maintenance Treatment With iPARP in First-Line Ovarian Cancer

LEOPARD Training and Validation Data Collection Study

FIH Trial of VERT-002 in Patients With Locally Advanced or Metastatic Solid Tumors With MET Alterations

Randomized Phase III Trial Testing Maintenance Olaparib Versus Observation After Adjuvant Chemoradiation for P53abn Endometrial Cancer

Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302)

Lymphocyte Support to SBRT in Patients With Oligo-metastatic Solid Cancer

Ablative radiotherapy - also called stereotactic body radiation therapy (SBRT) - can achieve durable control of tumor lesions and appears as a highly promising strategy to extend overall survival of patients with oligo-metastatic diseases. Radiotherapy has recognized immunomodulatory effects: it triggers immunogenic cell death and reprogramming of the tumor immune microenvironment, which eventually results in a systemic antitumor response following focal radiation treatment. This is called the abscopal effect (distant out-of-the-field lesions that shrink after focal irradiation). Unfortunately, evidences show that this is directly counteracted by the toxic effects of radiotherapy on cytotoxic lymphocytes, which are highly radiosensitive. Recent data support the fact that radiation-induced lymphopenia is mostly driven by the deregulation of the myeloid-lymphoid imbalance following radiation therapy, with aberrant myelopoiesis and high levels of tumor infiltration by myeloid-derived suppressive cells (MDSC). In preclinical models, pharmacological blockade of MDSC combined with radiation therapy successfully abrogated radiation-induced lymphopenia and significantly improved survival outcomes. All trans retinoic acid (ATRA, also known as tretinoin) is a vitamin A derivative that has a market authorization for the treatment of acute promyelocytic leukemia as it efficiently induces differentiation of abnormal promyelocytes. Similarly, several clinical studies report that ATRA can differentiate MDSCs into mature myeloid cells, with a positive effect on the count of activated cluster of differentiation 8 (CD8+) lymphocytes. This clinical trial will provide the clinical proof-of-concept that adding ATRA to pan-metastases SBRT is safe in humans, prevents severe and prolonged lymphopenia and therefore, may foster a radiation-induced systemic anticancer immune response sufficient to increase survival in patients with cancer at the oligo-metastatic stage.

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 to neoadjuvant chemotherapy (NACT). Despite the substantial outcome improvements achieved with neoadjuvant chemotherapy-based strategies, at least 50-60% of patients with TNBC do not 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 from the end of (neo)adjuvant treatments. Overall, 20-25% of patients with TNBC develop an early recurrence at ≤ 12 months from the end of (neo)adjuvant chemotherapy. Neither standard chemotherapy options nor approved targeted therapies exist for 35.000-40.000 women/year with TNBC (≈1200 women/year in France) that progress during (neo)adjuvant treatment 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 of innovative strategies, with immunotherapy or targeting therapies in combination with chemotherapy. The treatment algorithm in 1st line is often based on the use of platine-containing regimens that provide very low response rates (less than 15%), no more than 2-3 months of 1st-line PFS and a median OS of about 9 months. Yet, comprehensive genomic analyses performed over the past years on patients with residual disease after neoadjuvant chemotherapy have not introduced concrete findings for guiding drug development in this setting. Comparisons of initial biopsies with post-NACT tumor tissues revealed a wide range of profound tumor changes acquired under the selective pressure of NACT that encompass the development of dominant subclones, tumor immune depletion and stem-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 the different patterns involved. The idea is to set a rapidly recruiting phase I-II trials allowing to explore new treatment-strategies in patients with early recurrent and highly refractory TNBC have the potential to fulfil this utmost and urgent medical need.