Endometrial Cancer

The primary purpose of this study is to determine whether the investigational drug XmAb541 is safe and well tolerated, and to determine an optimal and safe dose(s) for further study. The study will also evaluate the effect of XmAb541 on tumor outcomes.

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 (with or without measurable disease) 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 objective of this study is to evaluate the safety, tolerability, and efficacy of BL-M07D1 in patients with HER2 expressing advanced tumors.

The purpose of this study is to compare how well Rina-S (GEN1184) works compared to treatment of physician's choice (paclitaxel or doxorubicin) that are considered standard medical care for the treatment of recurrent or progressive endometrial cancer (EC) following prior therapy. There is an equal (50:50) chance of getting either Rina-S or a chemotherapy agent as treatment in this study. The study duration will be approximately 3 years. The treatment duration will be different for every participant, but an average of 4 to 6 months is expected. All participants will receive active drug; no one will be given placebo. Participation in the study will require visits to the study site(s).

RAINBO MMRd-GREEN is an international, multicenter, phase III randomised trial wherein adjuvant pelvic external beam radiotherapy combined with and followed by durvalumab for one year is compared to adjuvant pelvic external beam radiotherapy with or without chemotherapy.

This is a pragmatic, non-inferiority randomized hybrid decentralized clinical trial. The goal of this study is to determine if one year of maintenance immunotherapy (anti-PD1 agent therapy; pembrolizumab or dostarlimab) is non-inferior to two years of maintenance therapy for patients with advanced/metastatic or recurrent endometrial cancer who have completed the standard course of cytotoxic chemotherapy plus anti-PD1 therapy (chemoimmunotherapy). Our hypothesis is that one year of maintenance therapy will be comparable, or statistically non-inferior, to two years of therapy. This question has clinical importance as there is not a clear optimal duration for maintenance immunotherapy in this setting, and checkpoint inhibitors are associated with their own unique toxicity profile (immune-related adverse events) and incremental costs to patients and the healthcare system at large. Patients who respond favorably to primary therapy and choose to enroll will be randomized (1:1) after completion of chemoimmunotherapy to one-year of maintenance anti-PD1 therapy (1-year arm) or to two-years of maintenance anti-PD1 therapy (2-year arm). The primary endpoint is progression-free survival (PFS) determined over the course of at least 3 years from randomization of patient follow up. Secondary endpoints are overall survival (OS) and incidence of immune-related adverse events (irAE). Finally, exploratory objectives include measuring differences in gut and vaginal microbial profiles and innate immune system (IIS) tumor profiles and correlation with clinical outcomes (PFS, OS).

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).

The goal of this clinical trial is to evaluate the efficacy of proactive immune tolerance induction of chemotherapy (paclitaxel and carboplatin) for patients with gynecologic cancer. The main questions it aims to answer are: \- Does immune tolerance induction during the first three cycles of chemotherapy reduce the incidence of hypersensitivity reactions in the remaining cycles? Participants will: * Undergo immune tolerance induction or standard treatment during the first three cycles of chemotherapy as randomized, after which all participants will continue the remaining cycles with standard treatment. * Receive a reduced dose of dexamethasone premedication if assigned to the experimental group, depending on the specific protocol of each clinical trial.

Researchers are looking for new ways to treat people with proficient mismatch repair (pMMR) endometrial cancer (EC) that is advanced or recurrent. * EC is a type of cancer that starts in the tissues inside the uterus (womb) * pMMR indicates that certain normal proteins are present in the cancer cells * Advanced means the cancer has spread locally or to other parts of the body (metastatic) and cannot be removed with surgery * Recurrent means the cancer came back after surgery Sacituzumab tirumotecan (also known as sac-TMT) and pembrolizumab are the study medicines. Sac-TMT is an antibody drug conjugate (ADC). An ADC attaches to specific targets on cancer cells and delivers treatment to destroy those cells. The goal of this study is to learn if people who receive sac-TMT with pembrolizumab live longer and without the cancer getting worse compared to people who receive pembrolizumab alone.

This research is designed to determine if experimental treatment with Antibody-drug conjugate, AZD5335, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced tumors

This is a Phase 1, open-label, first-in-human study of CTX-10726 monotherapy in patients with metastatic or locally advanced malignancies. The study will be conducted in 2 Cohorts: Cohort 1 Dose Escalation and Cohort 2 Dose Expansion.

This clinical trial studies whether an exercise program can be successfully delivered to patients receiving treatment for cancer through virtual sessions and allow patients to exercise in their own home. Treatments for cancer can cause side effects such as fatigue and loss of strength. These side effects can make it difficult to work, take care of family, and do other things the patient wants to do. Preliminary research shows that exercise can help prevent some of these side effects, but it can be more difficult to start an exercise program when a patient is receiving cancer treatment. The exercise program in this study is delivered through telehealth (TH) video calls. The TH sessions are delivered by trained staff that supervise resistance exercises. The trained staff also provide guidance to the patient on completing unsupervised aerobic sessions on their own. This may be a successful way to deliver an exercise program and make it easier for cancer patients to exercise in their own home during treatment.

The Phase 2 monotherapy portion of this study is currently enrolling and will evaluate the efficacy and safety of PC14586 (INN rezatapopt) in participants with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation. The Phase 1 portion of the study will assess the safety, tolerability and preliminary efficacy of multiple dose levels of rezatapopt as monotherapy and in Phase 1b in combination with pembrolizumab.

Study Objectives This study aims to investigate the effects of preoperative stellate ganglion block and intraoperative intravenous dexmedetomidine on postoperative sleep disturbance in patients undergoing laparoscopic gynecologic surgery, with the goals of reducing pain and postoperative adverse reactions and identifying an effective, safe, economical, and broadly applicable intervention strategy that may facilitate emergence from anesthesia, accelerate postoperative recovery, shorten the length of hospital stay, and reduce hospitalization costs. This trial aims to determine whether preoperative stellate ganglion block (SGB) and intraoperative intravenous dexmedetomidine (DEX) can improve postoperative sleep quality in patients undergoing laparoscopic gynecologic surgery, and whether the combination of these two interventions provides an interaction effect or additional ben

This is a multi-center, first-in-human (FIH), open-label, Phase 1a/1b dose escalation and dose expansion study to assess the safety, PK, pharmacodynamics, and antitumor activity of PHST001 monotherapy (Phase 1a) or in combination with anticancer therapies (Phase 1b) in adult participants with advanced relapsed and/or refractory solid tumors (including but not limited to CNS tumors in Phase 1a only). Phase 1b will include the following cohorts 1) tumor-specific cohorts for participants with advanced relapsed and/or refractory ovarian cancer, endometrial cancer, and cholangiocarcinoma, 2) a randomized cohort for participants with ovarian cancer who will receive PHST001 in combination with mirvetuximab soravtansine, 3) a cohort for participants with advanced/metastatic breast cancer who will receive PHST001 in combination with trastuzumab deruxtecan and 4) a cohort of patients who consent to additional biomarker studies. The study's primary objectives are to evaluate the safety and tolerability of PHST001 and determine the RP2D (Recommended Phase 2 dose) of PHST001 as monotherapy and in combination with anticancer therapies, as well as to assess the anti-tumor activity of PHST001 in combination with anticancer therapies in Phase 1b.

The incidence of endometrial cancer is increasing at an alarming rate. This trend parallels the rising rate of obesity, the most significant risk factor for endometrial cancer. Young women with obesity and endometrial cancer or atypical hyperplasia who want to maintain their fertility are treated with progestin therapy, such as progestin intra-uterine device (pIUD), which is associated with a mediocre response rate and high recurrence rate, and does not address the underlying cause, obesity. Therefore, the investigators want to assess whether the addition of a weight-loss drug to pIUD will improve their oncologic, reproductive and metabolic outcomes.

The goal of this clinical trial is to learn if a combination treatment of a hormonal intrauterine device (LNG-IUD), semaglutide, and a structured weight loss program can treat endometrial atypical hyperplasia or grade 1 endometrioid endometrial cancer while preserving fertility in women of reproductive age with endometrial atypical hyperplasia (EAH) or FIGO grade 1 endometrioid endometrial cancer who wish to preserve their fertility. The main questions it aims to answer are: * What proportion of participants achieve a complete pathological response after treatment? * How durable is the response at 12 months? * What effect does the treatment have on metabolic outcomes (weight, BMI, HbA1c) and quality of life? Participants will: * Receive an LNG-IUD * Receive semaglutide 2.4mg * Participate in a structured weight loss program * Undergo hysteroscopy with endometrial sampling to assess treatment response * Complete quality-of-life assessments at baseline, 6 months, and 12 months

A Phase 1, First-in-Human (FIH), Open-Label, Dose-Escalation and Dose Expansion Study of the Peptide Drug Conjugate (PDC), TS-104, as a Monotherapy in Subjects with Select Advanced Solid Tumors. The main goals of this study are to: * Find the recommended dose of TS-104 that can safely be given to participants * Learn more about the side effects of TS-104 * Learn more about the effectiveness of TS-104 * Learn more about the pharmacokinetics of TS-104

This is a Phase 1/2a dose escalation and expansion study to determine the safety, tolerability, and preliminary clinical activity of 177LuBetaBart, a lutetium-labeled anti-B7-H3 monoclonal antibody, in patients with relapsed/refractory, locally advanced inoperable, or metastatic solid tumors

This is a German multi-center, prospective, non-interventional study (NIS) to collect real-world clinical data in patients with primary advanced (FIGO stage III or IV) or recurrent endometrial cancer (EC) receiving first-line (1L) regimens with Carboplatin/Paclitaxel/Durvalumab (CPD) followed by maintenance therapy with durvalumab or durvalumab and olaparib in line with the applicable european summary of product characteristics (SmPC). Additionally, patient-reported outcomes after 1L treatment with CPD will be assessed.

LCCC2415 examines the antiproliferative effect of tirzepatide on the endometrium of endometrial cancer (EC). This is a pre-operative window clinical study. Endometrial biopsy samples from patients before tirzepatide treatment will be compared to their post-intervention hysterectomy specimens. If archival tissue is unavailable, a fresh biopsy will be taken before tirzepatide treatment. Post-intervention tissue will be collected from the hysterectomy specimen. The hypothesis is that tirzepatide's anti-tumorigenic effects are due to both an improvement in the host's metabolic milieu (indirect effect) and a direct effect on the EC tumor microenvironment via the inter-related pathways of insulin, lipid, and mTOR signaling. Therefore, tirzepatide may be an innovative approach to effectively induce weight loss and inhibit tumor growth in EC, the most obesity-driven of all cancers.

This is a proof-of-concept study designed to investigate HER3-DXd monotherapy in locally advanced unresectable or metastatic solid tumors. The study is enrolling cohorts of participants with melanoma \[cutaneous/acral\], squamous cell carcinomas of the head and neck (SCCHN), HER2-negative gastric cancer ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, prostate cancer, second-line gastric cancer, lung cancer, and breast cancer.

The goal of this study is to determine the anti-proliferative effect of tirzepatide on the endometrium of patients with endometrial intra-epithelial neoplasia (EIN) and Grade 1 endometrial cancer (EC), by comparing archival endometrial biopsy samples of patients randomized to tirzepatide versus SOC (no tirzepatide) to their post-intervention hysterectomy specimens. It was hypothesized that tirzepatide may help fight tumors in two ways: indirectly, by improving the body's overall metabolic health, and directly, by acting on abnormal cells in the uterus, such as those found in endometrial intraepithelial neoplasia (EIN) and endometrial cancer (EC). EIN is considered a precursor to EC. Tirzepatide may influence the tumor environment through key biological pathways related to insulin, fat metabolism, and mTOR signaling, all of which are often disrupted in individuals with obesity. Because both EIN and EC are strongly linked to obesity, tirzepatide could offer a promising dual benefit, promoting weight loss while also slowing or stopping tumor growth. The primary goal of this study is to determine whether tirzepatide can reduce cell proliferation in the lesions or tumors of patients with EIN and early- stage (Grade 1) EC. Patients will either be randomized to receive tirzepatide or no tirzepatide for 4 weeks prior to their hysterectomy surgery. Patients randomized to the tirzepatide arm will be given a glucose monitoring system for continuous monitoring with real-time alarms to alert of hypoglycemia. Patients will complete diaries during treatment to document compliance with medication and record any side effects. Patients will undergo standard of care surgery 7-10 days after the final dose of tirzepatide in order to minimize the risk of gastroparesis. During surgery (hysterectomy), an endometrial biopsy for uterine biopsy tissue will be collected. At the 1-month post-operation visit, patients from both arms will be referred to an institutional weight loss clinic.

The overarching objective of this project is to develop a pan-gynecologic cancer detection test using gynecologic (unique endometrial, cervical, and ovarian cancer) cancer-specific methylated DNA markers and high-risk human papilloma virus (HR-HPV) detected in vaginal fluid and/or plasma. This proposal defines Phase II MDM-based cancer detection studies in endometrial cancer (EC) and endometrial hyperplasia with atypia (AEH) in vaginal fluid and 2) ovarian cancer (OC) in plasma and vaginal fluid. Additionally, it defines necessary Phase I MDM-based cancer detection and exploratory aims to test novel cervical cancer (CC) MDMs and test the specificity of cancer-specific MDMs among various common benign gynecologic pathologies.er detection and exploratory aims to test novel cervical cancer MDMs and test the specificity of cancer-specific MDMs among various common benign gynecologic pathologies.

The researchers are doing this study to evaluate the use of circulating tumor DNA (ctDNA) testing in making treatment decisions for advanced/recurrent endometrial cancer that has a change (mutation) in the mismatch repair deficient (MMR-D) gene or microsatellite instability high (MSI-H) gene. The researchers will see how doctors and their patients use the results of ctDNA testing after 1 year of standard chemotherapy and immune checkpoint inhibitor (ICI) treatment to decide whether to continue maintenance ICI treatment past 1 year. The researchers will also look at the health outcomes of people in this study (for example, whether they are cancer free at the end of their participation in the study).