Castello D Aviano

Researchers are evaluating a chemo-free combination of rituximab and golcadomide (CC-99282) as a front-line treatment for older, frail patients newly diagnosed with diffuse large B-cell non-Hodgkin lymphoma (DLBCL). This phase II, multicenter study focuses on patients aged 80 or older who are considered frail based on a simplified geriatric assessment (sGA) and are not eligible for standard anthracycline-based chemotherapy. The study aims to assess the effectiveness of this treatment approach in this vulnerable population. Participants will receive an induction phase of up to six 28-day cycles consisting of golcadomide, rituximab, and dexamethasone only during the first cycle. Response to treatment will be evaluated after four and six cycles to identify patients who are responding. Those achieving at least a partial response will continue as planned, while non-responders will stop protocol treatment and switch to alternative regimens. After induction, involved site radiotherapy is permitted for PET-positive disease. Patients with at least partial response at the end of induction may then enter a consolidation phase with up to six additional 28-day cycles of golcadomide. Interim response checks during consolidation will identify disease progression, leading to treatment discontinuation if needed. Throughout the study, participants will undergo assessments including PET/CT or CT scans to evaluate disease and sarcopenia at baseline and end of treatment. Quality of life will be measured at study entry, during treatment, and follow-up. Follow-up visits will occur every three months for the first year and every six months in the second year, with a total follow-up duration of 24 months. Progression-free survival at 24 months is the primary outcome. Patients with disease progression will be considered treatment failures and followed for survival until study completion.

Researchers are studying BAY 3713372, a new drug being developed to treat solid tumors with a specific genetic change called MTAP deletion. The drug works by blocking a protein called PRMT5, which may kill cancer cells with this deletion while sparing normal cells. This first-in-human study aims to understand the safety, how the body processes the drug, and its effectiveness in people with these MTAP-deleted solid tumors. Participants will receive BAY 3713372 orally every day. The study starts with a dose escalation phase, where different groups get increasing doses to find a safe and effective dose. After this, a dose expansion phase will include more participants receiving the drug alone or with other treatments. Participants can continue treatment as long as they benefit and do not experience severe problems. During the study, participants will visit the study site multiple times before and during treatment, and follow-up visits after treatment ends. Doctors will monitor health through blood and urine tests, heart checks with electrocardiograms, and imaging scans like CT or MRI to track cancer changes. Tumor samples may also be taken. Safety and treatment response will be closely assessed, including adverse events and how the drug behaves in the body. Participants will be contacted every three months for up to two years after treatment to check their health.

The trial investigates the use of volrustomig in participants with unresected locally advanced head and neck squamous cell carcinoma (LA-HNSCC) who have not shown disease progression after receiving definitive concurrent chemoradiotherapy (cCRT). The study aims to evaluate the efficacy and safety of volrustomig compared to observation in this patient population. Participants have tumors that express PD-L1 and the study is conducted as a Phase III, randomized, open-label, multi-center global trial. Participants are assigned to receive either volrustomig as sequential therapy following cCRT or to an observation group. The treatment period involves monitoring participants who have completed definitive cCRT but remain unresected and have no evidence of metastatic disease. The study focuses on participants with Stage III, IVA, or IVB LA-HNSCC according to AJCC criteria, who have not undergone tumor resection before cCRT and have not been treated with radiotherapy alone. During the study, participants are regularly evaluated for progression-free survival, with follow-up lasting up to approximately 8 years to assess long-term outcomes. Researchers will monitor safety and disease progression closely. The overall participation duration includes screening, treatment or observation, and extended follow-up to capture both efficacy and safety data over time.

Researchers are evaluating the effectiveness and safety of ACR-368 alone or combined with ultra-low dose gemcitabine (ULDG) sensitization in people with endometrial cancer. This is an open-label Phase 2 study involving participants with high-grade endometrial adenocarcinoma. Participants are grouped based on a test called OncoSignature, which predicts sensitivity to ACR-368, or by tumor subtype without requiring the test. Participants in Arm 1 and Arm 4 receive ACR-368 as a single treatment, while those in Arms 2 and 3 receive ACR-368 combined with ULDG sensitization. Arms 1 and 2 are for participants selected by OncoSignature status, while Arms 3 and 4 include participants with serous carcinoma regardless of OncoSignature results. Treatment continues until the disease progresses, unacceptable side effects occur, or the participant withdraws. Participants will have tumor response assessed every 8 weeks from the start of treatment through two years or until death. To join, participants must have measurable metastatic cancer that progressed after prior therapies, provide tumor tissue samples, and meet health and organ function requirements. Safety and response will be closely monitored throughout the study.

Researchers are conducting a large prospective, observational cohort study to assess the clinical impact of new monoclonal antibodies (MAB) in treating B-cell Non-Hodgkin Lymphoma (NHL) within Italian clinical practice. The study focuses on patients needing treatment for B-cell NHL, including those receiving first-line or relapsed/refractory therapy. The novel MAB being studied have received approval from the European Medicines Agency (EMA) since 2020 and are prescribed according to authorized marketing indications in Italy. Participants will receive novel MAB treatments either alone or in combination, prescribed based on EMA-approved indications since 2020. Patients will be grouped into cohorts according to the treatment indication, antibody type, and lymphoma subtype, with additional sub-cohorts created if necessary. This design allows analysis by indication, antibody type, subtype, and overall evaluation of the entire patient cohort. Throughout the study, researchers will collect clinical information to evaluate the use, feasibility, efficacy, and toxicity of these novel antibodies. Key outcomes measured over at least five years include overall response rate, complete response rate, progression-free survival, overall survival, event-free survival, time to next treatment, non-relapse mortality, duration of response, and incidence of early and late adverse events. Participants will be closely monitored for both short- and long-term effects of the treatments.

Researchers are conducting a phase III randomized, open-label, multicenter trial across several countries including Sweden, Norway, Finland, Denmark, Italy, Australia, and New Zealand. The study focuses on elderly patients with untreated diffuse large B-cell lymphoma (DLBCL), defined as patients aged 80 years or older, or those aged 75 years or older who are considered frail based on a simplified Comprehensive Geriatric Assessment. The trial aims to compare the effectiveness of two treatment regimens in this population. Participants are randomly assigned to receive either the standard R-miniCHOP treatment or an experimental R-pola-miniCHP regimen where vincristine is replaced with an immunoconjugate, polatuzumab vedotin. Both treatments involve cycles of drugs including rituximab, cyclophosphamide, doxorubicin, and prednisone, administered over 18 weeks. The trial includes a screening period lasting up to 4 weeks, followed by the active treatment phase, and then a follow-up period lasting up to 36 months after treatment completion. Throughout the study, participants will be monitored to measure progression-free survival over 2 years as the primary outcome. The study involves regular assessments including clinical evaluations and safety monitoring. Enrollment began in the first quarter of 2020, with the last patient visit expected by the first quarter of 2027, allowing for long-term observation of treatment effects and patient outcomes.

Researchers are evaluating the effectiveness and safety of zanidatamab combined with a physician's choice of chemotherapy compared to trastuzumab combined with chemotherapy in treating adults with metastatic HER2-positive breast cancer. This study focuses on participants whose cancer has progressed or who cannot tolerate previous treatment with trastuzumab deruxtecan (T-DXd). The study is a phase 3 randomized trial aiming to assess progression-free survival and other important outcomes such as patient-reported tolerability and physical functioning. Participants receive either zanidatamab or trastuzumab through intravenous infusion, alongside chemotherapy drugs chosen by their physician from eribulin, gemcitabine, vinorelbine (all intravenous), or oral capecitabine. The study includes detailed monitoring of drug safety and how the body processes zanidatamab. The treatments continue until disease progression or unacceptable side effects occur. During the study, participants undergo regular evaluations including scans to measure cancer progression according to RECIST guidelines. Researchers also monitor safety through laboratory tests and heart function assessments. Participants are followed for up to approximately 44 months to measure progression-free survival and overall treatment outcomes. Long-term follow-up and patient-reported outcomes help provide a complete understanding of the treatments' effects.

Researchers are evaluating the safety and effectiveness of divarasib combined with pembrolizumab compared to pembrolizumab with pemetrexed and either carboplatin or cisplatin. The study focuses on adults with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that has a specific KRAS G12C mutation. This is a Phase III trial aiming to improve first-line treatment options for these patients. Participants will receive one of two treatment combinations. One group will take divarasib orally once daily along with pembrolizumab given through an intravenous infusion every three weeks. The other group will receive pembrolizumab with pemetrexed and either carboplatin or cisplatin, all administered by intravenous infusion every three weeks. Treatment schedules and dosages are carefully monitored during the study. Throughout the study, participants will be regularly assessed for progression-free survival and overall survival, with follow-up lasting up to approximately five years. Researchers will perform various evaluations including tumor measurements and safety monitoring. This long-term observation helps to understand the treatments' effects and safety over time, supporting informed decisions for future lung cancer therapies.

This research aims to evaluate the safety and effectiveness of the combination of avutometinib and defactinib compared to standard treatments chosen by investigators in women with recurrent low-grade serous ovarian cancer (LGSOC) who have experienced disease progression after prior platinum-based therapy. Both avutometinib and defactinib are investigational kinase inhibitors designed to block cancer cell growth. The study will also assess overall survival, other measures of treatment effectiveness, safety, and quality of life impacts. Participants will be randomly assigned to receive either the combination of oral avutometinib and defactinib or one of four standard treatments recommended for recurrent LGSOC: pegylated liposomal doxorubicin and paclitaxel (both given intravenously), or the oral drugs letrozole or anastrozole. Patients treated with standard therapies who experience disease progression may be eligible to switch to the investigational combination. The study is open-label and conducted internationally by specialists in gynecological cancer. Throughout the study, participants will have regular follow-up visits including scans and tests to measure disease progression, with a primary focus on progression-free survival up to 24 months. Researchers will monitor safety, side effects, and overall survival while collecting information on quality of life and symptoms. The study involves ongoing assessments of treatment effects and participant health until the study concludes or disease progression occurs.

Researchers are evaluating the efficacy and safety of a drug called azenosertib (ZN-c3) in women with platinum-resistant, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. This Phase 2 study focuses on patients whose tumors test positive for Cyclin E1 protein, determined by a specific assay developed by the sponsor. The study aims to understand how well azenosertib works in this group and its safety profile. The study involves administering azenosertib orally to participants. It is divided into two parts: Part 1 included all patients regardless of biomarker status and has completed enrollment; Part 2 requires tumors to be Cyclin E1 positive. Participants receive azenosertib and are monitored throughout the study according to the protocol. Participants will be involved in various assessments including tumor measurements following RECIST version 1.1 criteria up to about 12 months after the last participant enrolls. Researchers will track the objective response rate to evaluate tumor response. Safety and efficacy evaluations, along with monitoring of side effects and overall health, will take place during the study period to gather comprehensive data on the treatment.