Endometrial Neoplasms

The goal of study： The study has two parts: Part 1 Dose Escalation and Part 2 Dose Expansion. In Part 1, a few participants will receive the lowest dose of study drug. The study team will make sure it is safe and tolerated before enrolling new participants at a higher dose of study drug. There will be up to six or more dose levels of study drug tested (called cohorts). Which dose you receive will depend on how many participants have taken part in the study before you. The purpose of Part 1 of the study is to evaluate the safety of the study drug at different dose levels, to understand what your body does to the study drug, and to find the best dose of study drug in people who have advanced solid tumor cancers. In Part 2, participants will receive the best dose level that was determined in Part 1 of the study. The purpose of Part 2 of the study is to evaluate the safety of the study drug at the dose level determined in Part 1, to understand what your body does to the study drug, and to see how your cancer responds to the study drug. Participants will: Participants will have 17 or more visits to the study centre. This study has a screening phase of up to 28 days , and a treatment phase with cycles of 21 days each. Participants will also have an End of Treatment (EOT) visit 21 days after the final study drug treatment, and a Follow-up visit 30 days after the EOT visit . Participants will be contacted by telephone every 3 months after the Follow-up visit to check on the wellbeing and record any new anticancer therapy they may have started.

The main purpose of this study is to evaluate safety, tolerability, and efficacy of LY4257496 alone and as part of relevant standard of care (SOC) combination therapy in participants with Gastrin-releasing Peptide Receptor (GRPR)-positive advanced cancer, including but not limited to breast, colorectal, prostate, endometrial, esophageal, gastroesophageal (GE) junction, and gastric cancer. The study will also evaluate the safety, tolerability, and efficacy of LY4257529 to identify cancer with high levels of a protein called GRPR. This is a 2-part study. Participation could last up to 36 weeks or until your tumor progresses.

The purpose of this study is to measure the safety and efficacy of LY4175408 in participants with selected advanced cancer. In addition, this study will evaluate how much LY4175408 gets into the bloodstream, how it is broken down, and how long it takes the body to get rid of it. Participation could last up to 4 years.

The purpose of this study is to find out whether the study drug, LY4170156, is safe, tolerable and effective in participants with advanced solid tumors. The study is conducted in two parts - phase Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). The study will last up to approximately 4 years.

This study is being conducted to assess whether the study medicine PF 08634404, given in combination with chemotherapy, improves outcomes compared with another medicine called pembrolizumab plus chemotherapy. Chemotherapy is a type of cancer treatment that uses medicines to destroy cancer cells or stop them from growing. Our bodies have a built-in DNA "spell-checker," called the mismatch repair (MMR) system, that fixes genetic mistakes. In most endometrial cancers, this system works normally, and these cancers are called MMR-proficient (pMMR). However, pMMR tumors are harder for the immune system to recognize and attack. When endometrial cancer has spread beyond the uterus or comes back after previous treatment, it is called advanced or recurrent endometrial cancer. This study is for adults with mismatch repair-pMMR advanced or recurrent endometrial cancer. Participants must meet key criteria, including: * Women who are 18 years or older, and not pregnant at the time of joining the study * pMMR endometrial cancer only * Measurable Stage III disease, Stage IV disease (with or without measurable disease) per FIGO staging, a system doctors use to describe how far cancer has spread in the body, or recurrent endometrial cancer * Has not received chemotherapy except for chemotherapy given after the main surgery and more than 6 months before relapse * Be in good enough health to receive study treatment. Approximately 600 adult women will be enrolled. Each participant will be randomly assigned (like a flip of the coin) to one of two treatment groups, with about half in each group. The study is open, meaning both the doctors and participants know what treatment is being given. Participants will receive their assigned treatment through intravenous infusions (medicine is given directly into a vein). The treatment will be given in cycles. Experimental Group will receive new study medicine called PF-08634404 plus chemotherapy. It will be followed by PF 08634404 alone for up to 2 years (35 cycles). Control Group will receive an approved medicine called pembrolizumab plus chemotherapy. It will be followed by pembrolizumab alone for up to 2 years (20 cycles). The study will include regular visits for: * Participants will have regular visits to the study site for treatment, health checks, and tests. * After stopping treatment, participants will come for a final visit within a month to check their health and review any reactions. * Follow-up will continue every 12 weeks by phone or in person or by reviewing health records. This helps check health and any new treatments. * Tests will be done every 9 weeks during the first 104 weeks to see how the cancer is responding. After that, tests will be done every 12 weeks.

The goal of this clinical trial is to learn if Trastuzumab Rezetecan can treat advanced solid tumors with HER-2 expression in adult participants. The main question it aims to answer is: What is the objective response rate of Trastuzumab Rezetecan in adult patients with HER-2 expressed advanced solid tumors? Participants will receive intravenous infusion of Trastuzumab Rezetecan on Day 1 of each 21-day treatment cycle. The dosage is 4.8 mg/kg per cycle; participants with a body weight of 85 kg or above will receive a fixed dose of 408 mg every 3 weeks.

Multicenter, randomized, open-label, phase II clinical study comparing Dostarlimab +/- Bevacizumab with standard chemotherapy in patients with gynecological clear cell carcinoma. 198 subjects will be enrolled in this study and will be assigned to three groups in a 1:1:1 ratio. 1. Group A: Dostarlimab monotherapy * First 3 cycles: Dostalimab 500mg every 3 weeks, IV * 4 cycles \~ up to 24 months: Dostalimab 1000mg every 6 weeks, IV 2. Group B: Dostarlimab + Bevacizumab combination therapy * First 3 cycles: Dostalimab 500mg every 3 weeks, IV * 4 cycles \~ up to 24 months: Dostalimab 1000mg every 6 weeks, IV * Bevacizumab administered IV at 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity 3. Group C: General chemotherapy (one of Pegylated liposomal doxorubicin, Doxorubicin, Paclitaxel, and Gemcitabine)

Minimally invasive surgery is the recommended approach in endometrial cancer (EC) patients based on the results of two randomized controlled trials, given its advantages without compromised oncologic outcomes. The uterine manipulator is commonly used in benign and malignant pathologies to perform a laparoscopic or robotic hysterectomy. However, although regularly used, the uterine manipulator adoption in EC is a controversial technical aspect due to the raised concerns regarding the possible risk of disruption of the tumor mass, the spread of malignant cells, and seeding of the disease, particularly at the level of the vaginal cuff or spread of tumor cells, with increased risk of recurrence and death due to EC. On that basis, given that hysterectomy without a uterine manipulator is feasible, only a randomized controlled trial comparing oncologic outcomes in EC patients after use versus not use of the uterine manipulator will be able to provide high-quality evidence to answer this critical question and allow or exclude the use of a uterine manipulator during minimally invasive hysterectomy for EC.

The goal of this clinical trial is to evaluate the efficacy and safety of cadonilimab in combination with paclitaxel, cisplatin, and radiation therapy for the treatment of locally recurrent and oligometastatic endometrial carcinoma. The main questions it aims to answer are: 1. Does the combination therapy improve the overall response rate (ORR), progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety in participants? 2. What are the predictive biomarkers of treatment efficacy, and how can this information better guide the use of immune-oncology drugs in combination therapy? Participants will: * Receive cadonilimab, paclitaxel, cisplatin, and radiation therapy according to a specified protocol. * Visit the clinic for regular checkups and tests throughout the treatment period. * Be monitored for and have records kept of ORR, PFS, DCR, OS, and safety. * Provide hematologic and tissue samples to explore biomarkers. This study will help determine if this combination therapy can become a new standard of care for patients with locally recurrent and oligometastatic endometrial carcinoma, as well as identify biomarkers to better guide treatment strategies.

The goal of the Dose Escalation phase of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion (RDE) of NKT3964 in adults with advanced or metastatic solid tumors. The goal of the Expansion phase of the study is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDE based on objective response rate (ORR) and determine the preliminary recommended Phase 2 dose (RP2D).

The purpose of the project is to set up a national, prospective, longitudinal, multicenter cohort study, a tumor registry platform, to document uniform data on characteristics, molecular diagnostics, treatment and course of disease, to collect patient-reported outcomes and to establish a decentralized biobank for patients with advanced or metastatic ovarian cancer (OC) or advanced or metastatic endometrial cancer (EC) in Germany.

The goal of this observational study is to evaluate the accuracy of a novel molecular test for screening and monitoring endometrial lesions in women at medium-to-high risk for endometrial cancer. The main questions it aims to answer are: * What is the sensitivity and specificity of the CISENDO test (a DNA methylation test on cervical cytology samples) for detecting histologically confirmed endometrial intraepithelial neoplasia (EIN) or invasive endometrial cancer? * How do DNA methylation levels change during the follow-up of endometrial lesions? Researchers will compare the results of the CISENDO test to the results from the standard diagnostic procedure (hysteroscopy with histology) to see if the molecular test can reliably identify high-risk lesions and track disease progression. Participants will: * Provide a residual liquid-based cervical cytology sample for the CISENDO test. * Undergo a standard diagnostic hysteroscopy examination (with or without biopsy) for comparison. * Some participants will return for follow-up visits at 6 and 12 months for repeat methylation testing and/or hysteroscopy to monitor their condition.

This clinical trial is looking at a drug called atezolizumab. Atezolizumab is approved as standard of care treatment for adult patients with urothelial cancer, non-small cell lung cancer, extensive-stage small cell lung cancer, hepatocellular carcinoma and triple negative breast cancer. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Atezolizumab works in patients with these types of cancers which have certain changes in the cancer cells called high tumour mutational burden (TMB) or high microsatellite instability (MSI) or proven (previously diagnosed) constitutional mismatch repair deficiency (CMMRD). Investigators now wish to find out if it will be useful in treating patients with other cancer types which are also TMB/MSH-high or show CMMRD. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future. This trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.

To investigate the efficacy of GnRHa plus letrozole in obese progestin-insensitive EEC patients.

To investigate the efficacy of GnRHa plus letrozole vs Diane-35 plus metformin in non-obese progestin-insensitive early-stage endometrial cancer (EEC) and atypical hyperplasia(EAH) patients asking for conservative treatment.

The actual role of POLE mutations in high-risk endometrial cancer is undetermined. The main question it aims to answer is: What is the prevalence of POLE mutations in high-risk endometrial cancer case? What is the impact of POLE mutations in real world high-risk endometrial cancer case?

This clinical trial evaluates lymph node mapping in newly diagnosed endometrial cancer patients undergoing surgery. The standard technique uses a 2-point methylene blue cervical injection. The study aims to determine if increasing injection points improves mapping success.

This study aims to develop and validate a test for detecting ovarian and endometrial cancers early. It relies on detecting somatic mutations that are associated with these cancers from a uterine pap test. A saliva sample is also collected that acts as an internal control and has the ability to detect deleterious germline mutations associated with common hereditary cancers (such as breast, ovarian, endometrial, colon, and pancreatic cancers). A machine learning classifier is then used to discriminate between cancer and benign disease.

phase 2 clinical trial to confirm the pathological complete response rate of PD-1 blocker use in patients with Mismatch Repair Deficiency(MMRd) endometrial cancer that can be completely resected surgically.

The goal of this study is listed below. Part A (Safety Run-in Phase) : To determine feasibility of pembrolizumab and nesuparib combination as maintenance therapy in patients with MMR-proficient advanced and recurrent endometrial cancer. Feasibility is defined as a dose-limiting toxicity (DLT) rate less than or equal to 33%. Part B (Randomization Phase) : To evaluate the efficacy of pembrolizumab and nesuparib combination/ pembrolizumab monotherapy as maintenance therapy in patients with MMR-proficient advanced stage and recurrent endometrial cancer. Efficacy will be assessed by investigator assessed progression free survival (PFS) as assessed by RECIST 1.1.

Data across literature suggest that robotic surgery may offer benefit specifically in patient with morbid obesity with endometrial cancer, but to date no randomized trials have been conducted to confirm these observations. This randomized controlled multicentric trial aims to evaluate the most appropriate minimally invasive surgical approach in morbidly obese (BMI \>= 30) patients with endometrial carcinoma.

The objective is to understand the relationship between TP53 mutation, MSS and chromosome instability in endometrial cancer and the effect on clinical prognosis.We will collect a small amount of tumor tissue samples. NGS panel detection and WGD/AS analysis were performed on the tissue. Paracancer tissue was used as a negative control and relevant information in medical records during the operation. Then we will collect clinical diagnosis and disease information through telephone follow-up after the completion of the operation.

The goal of this clinical trial is to evaluate the efficacy and safety of tislelizumab in combination with chemotherapy as a neoadjuvant treatment for advanced endometrial cancer.

Molecular typing provides accurate information for the diagnosis, treatment and prognosis prediction of endometrial cancer, which has important clinical significance. However, due to its high cost and complicated process, it is difficult to be widely used in clinical practice. Based on the artificial intelligence method, this study fused the characteristics of MRI radiomics and pathomics, combined with the clinical pathological information, built a model to predict the molecular typing and prognosis, analyzed the biological characteristics of endometrial cancer from the multi-scale level, guided the personalized and precise diagnosis and treatment, in order to improve the prognosis of patients.

The goal of this clinical trial is to explore the feasibility and outcome of fertility-sparing therapy in Stage IA G1-G2 Endometrial Cancer with less than 1/2 myometrial invasion. Researchers will render participants indication-extended fertility-sparing therapy. Researchers will compare the myometrial invasion group with the no myometrial invasion group to see if it is possible to propose an extension indication of fertility-sparing therapy for endometrial cancer.