Clinical Research Directory

Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001)

This study will test the safety, including side effects, and determine the characteristics of a drug called Rina-S in participants with solid tumors. Participants will have solid tumor cancer that has spread through the body (metastatic) or cannot be removed with surgery (unresectable).

A Study of IDE034 in Adult Participants With Locally Advanced/Metastatic Solid Tumors Types

This is a Phase 1a/1b, open-label, multicenter dose escalation and dose expansion clinical study to evaluate the safety, PK, immunogenicity and preliminary efficacy of IDE034 in participants with locally advanced/metastatic solid tumor types that express B7-H3 and PTK7.

Minimal Residual Disease in Solid Malignancies

The IMRD study is a single-centre, prospective observational study which will investigate the rate of ctDNA (circulating tumor DNA) detection from the start of adjuvant therapy following curative-intent surgery. The study will include patients of age 18 years old or older, who provided informed consent. Eligible patients are affected by one of the following non-metastatic resected tumors: i) breast cancer (BC), ii) non-oncogene addicted (EGFR/ALK-wild type) non-small-cell lung cancer (NSCLC), iii) high-risk and very high-risk prostate cancer, iv) high-grade serous ovarian cancer (HGSOC), and v) gastric cancer. Eligible patients will undergo surgery and receive adjuvant treatment(s) as per standard guidelines. Patients who underwent neoadjuvant treatments and had a complete pathological response (i.e., no residual tumor at surgery following neoadjuvant treatments) will not be eligible for the present study. During adjuvant treatment and following its conclusion, patients will be subjected to instrumental monitoring, as per standard guidelines and clinical practice. For eligible patients, a baseline plasma sample will be collected at the time of surgery (feasibility window) and prior to the start of adjuvant treatments (not prior to 28 from the date of surgery) for assessing the detection of ctDNA. Afterwards, plasma samples will be collected at 3, 6 and 9 months from the start of postoperative adjuvant treatments. For patient specific monitoring, a tumor-informed targeted sequencing panel, using tumor-specific mutations detected with WES, will be employed to gather the most sensitive diagnostic platforms, mitigating the risk of negative cases. At 6 months or upon positive ctDNA detection, either a thoracic-abdominal-pelvic or total-body CT scan will be performed to exclude the presence of overt metastatic disease. All patients included in the study will be monitored with longitudinal ctDNA assessment until one-year or follow-up or until the radiological detection of metastatic disease, whichever will occur first. Additional follow-up will be carried outside the IMRD study and will follow standard clinical protocols and schedules. Being an observational study, no treatment intervention will be applied as per protocol based on the detection or absence of ctDNA. For conducting exploratory analyses, the primary tumors will be retrieved and subjected to WES, and the study will aim to detect molecular tumor variables associated with a lack of ctDNA clearance following curative-intent treatment interventions. The study will be conducted in 2 phases. The first phase aims at verifying the feasibility and sustainability of such approach, based on the identification of at least 15% positive patients. This phase is predicted to be completed within 2 years, and is the object of the present application. If the first endpoint is achieved, we will expand the study to include the co-primary endpoint, which aims at estimating the fraction of patients with persistent ctDNA 6 months post-surgery despite adjuvant therapy.

A Phase 2 Study of Avutometinib (VS-6766) Plus Defactinib

The purpose of this research is to test the effectiveness and safety of the study drugs (VS-6766 and defactinib), and see what effects (good and bad) these drugs have on the patients with endometrioid cancer, mucinous ovarian cancer, high-grade serous ovarian cancer, or solid gynecological cancer.

Investigating Idetrexed and Olaparib in Patients With Ovarian Cancer

Two drugs called Idetrexed and olaparib are being evaluated. Idetrexed is a type of drug called an "aFR-targeted thymidylate synthase inhibitor". Idetrexed has been designed to selectively target cancer cells that have a protein called folate receptor on the surface of cancer cells. Thymidylate synthase is key to cancer cells for creating new DNA when they multiply. Blocking the action of thymidylate synthase with a drug like Idetrexed may therefore stop cancers from growing by damaging DNA in cancer cells. Olaparib is a type of drug called a "PARP inhibitor". It prevents cells repairing DNA damage. This leads to cells dying. Combining Idetrexed and olaparib should increase the number of cancer cells dying, especially those cells that have a lot of folate receptors. Cancer cells with a high number of folate receptors should be targeted more than normal healthy cells.

Unravelling Tumour Biology In Ovarian Cancer With Precision Imaging

The objective of this study is to explore the integration of in vivo and ex vivo of MRI with histology and molecular assessments to advance non-invasive characterization of tumor heterogeneity in high-grade serous ovarian cance

Role of RPL8 Protein Alterations in High-grade Serous Ovarian Carcinoma

Background and rationale of the study: From our preliminary analyses of a dataset on patients with high-grade serous ovarian carcinoma (HGSOC), available in the online database The Cancer Genome Atlas, we found that the gene encoding ribosomal protein L8 (RPL8) is amplified at a high frequency (\~30%) in HGSOC. Moreover, its mRNA expression is positively correlated with its genetic amplification-an observation not previously reported or studied in the literature. RPL8 is a structural component of the large ribosomal subunit, which is involved in protein synthesis. Based on this, and our preliminary data, we hypothesize that RPL8 amplification may play a role in ovarian cancer development. Understanding the impact of RPL8 amplification in ovarian cancer could provide new insights into the biology of this poorly understood cancer. Study objectives: The main objective of this project is to determine whether RPL8 can be used as a biomarker both for risk assessment and for patient stratification in choosing the most appropriate therapeutic option. Specifically, we aim to study: 1. The relationship between the genetic status of RPL8 and clinical outcomes. 2. The contribution of RPL8 amplification to treatment response. Type of human tissue under study: The analyses will be conducted on tumor tissue samples obtained from ovarian cancer resections. Some samples have already been collected and stored at the IRCCS, while others are yet to be gathered. Type of investigation: * Expression analysis of RPL8, C-MYC, and related genes (RT-PCR, ddPCR, WB, IHC). * Gene copy number analysis and mutation screening (ddPCR and similar molecular techniques). * Analysis of possible associations between pathological data, follow-up data, and therapeutic response outcomes in patients. Analysis methodology: Data on the genetic status, expression, and subcellular localization of RPL8 and C-MYC will be correlated with categorical and continuous variables related to the patients' medical history and clinical status. Differences between categorical variables will be analyzed using analysis of variance (ANOVA), the Mann-Whitney test, or the Kruskal-Wallis test, depending on whether data distribution is normal or not (assessed via the Kolmogorov-Smirnov test). Correlations between continuous variables will be evaluated using Pearson or Spearman tests, again based on data distribution.

"Re-Stimulated" TILs and IL-2 Therapy for Platinum Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

This is a phase I clinical study for patients with platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal cancer, and the response to a combination of cyclophosphamide, autologous tumor-infiltrating lymphocytes (TILs), autologous dendritic cells (DCs), and OKT3 (anti-CD3 antibody), along with low-dose interleukin-2 (IL-2) therapy.