Clinical Research Directory

Predicting Postoperative Chemotherapy Efficacy in Patients With Esophageal Squamous Cell Carcinoma

Esophageal cancer remains a disease with a poor prognosis. Chemotherapy is an important part of its treatment, but there are cases in which chemotherapy is ineffective. The investigators aim to develop a model to predict the response to chemotherapy by DNA methylation of preoperative biopsy specimens to identify the chemotherapy ineffective group.

A Study to Evaluate Efficacy and Safety of Tislelizumab Plus Chemotherapy for Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Adenocarcinoma and Esophageal Squamous Cell Carcinoma in Racial and Ethnic Minority Patients in the United States

The purpose of this study is to characterize the clinical effects of tislelizumab, including pharmacokinetics (PK), activity, and safety assessments in US racial and ethnic minority patients with human epidermal growth factor receptor 2 (HER2)-negative, programmed death-ligand 1(PD-L1)-positive, unresectable or metastatic gastric or gastroesophageal cancer (GAC/GEA) or esophageal squamous cell carcinoma (ESCC). The study duration will be up to approximately 6 years.

Becotatug Vedotin Plus Tislelizumab and Low-Dose Lenvatinib for Advanced Esophageal Squamous Cell Carcinoma, Phase II

Immunotherapy combined with chemotherapy has become the first-line standard of care for advanced esophageal squamous cell carcinoma (ESCC), significantly improving patient survival. However, with the widespread adoption of first-line immunotherapy, most patients eventually develop immune resistance. After first-line treatment failure, there is currently no established standard effective therapy for second-line ESCC. Therefore, more effective and safer treatment options are urgently needed for second-line advanced ESCC. This is a prospective, single-arm, single-center, open-label, Phase II clinical study aiming to evaluate the efficacy and safety of Becotatug Vedotin combined with Tislelizumab and low-dose Lenvatinib in patients with advanced ESCC who have failed first-line therapy. Eligible patients will receive Becotatug Vedotin combined with Tislelizumab and low-dose Lenvatinib. The primary endpoint is objective response rate (ORR) assessed per RECIST v1.1. Secondary endpoints include progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), overall survival (OS), and safety.

Cardenilimab Combined With Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma

The goal of this trial is to test the efficacy and safety of cardenilimab combined with chemotherapy in the conversion therapy of locally advanced unresectable esophageal squamous cell carcinoma. type of study: clinical trial

Becotatug Vedotin ± Anti-PD-1 in Pretreated Advanced ESCC

This study will test a new potential treatment for advanced esophageal squamous cell cancer (ESCC) for patients whose initial treatment has stopped working. Currently, the standard second-line treatment for this cancer is PD-1 inhibitors or chemotherapy alone, which is not very effective, allowing the cancer to grow again after just 1.6 to 3.4 months on average. Therefore, there is a strong need for more effective therapies. The new treatment is a type of drug called an antibody-drug conjugate (ADC). It is designed to target a specific protein called EGFR, which is found in high amounts on the surface of 50-70% of ESCC cancer cells and is linked to a poorer outlook for patients. This ADC works like a targeted delivery system: an antibody guides a powerful cell-killing drug directly to the cancer cells, aiming to destroy them while reducing harm to healthy cells. Although other drugs targeting EGFR have not successfully improved survival for ESCC patients, this new ADC offers a different and promising approach. The main goal of this study is to find out if this new EGFR-targeting ADC is effective in helping patients with advanced ESCC live longer without their cancer getting worse.

Substudy 06E: Umbrella Study of Combination Therapies in Esophageal Cancer (MK-3475-06E/KEYMAKER-U06)

Researchers are looking for new ways to treat esophageal squamous cell carcinoma (ESCC). ESCC is a type of cancer that starts in certain cells that line the esophagus. The esophagus is the tube that connects the throat to the stomach. This study will look at ESCC that is either locally advanced unresectable, which means it has spread into tissue near where it started and cannot be completely removed by surgery, or metastatic, which means it has spread to other body parts. Available treatments for these types of ESCC include pembrolizumab and chemotherapy. Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Chemotherapy is medicine that destroys cancer cells or stops them from growing. Researchers want to learn about giving pembrolizumab and investigational agents, with or without chemotherapy to treat ESCC. Ifinatamab deruxtecan (I-DXd), is an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. The main goal of this study is to learn about the safety of investigational agents and pembrolizumab with or without chemotherapy and if people tolerate them. Researchers also want to learn how cancer responds (gets smaller or goes away) to the study treatments.

A Study Evaluating the Safety, Efficacy, and Pharmacokinetics (PK) of EVOLVE104 in Participants With Advanced Urothelial and Squamous Cell Carcinomas

The goal of this study is to evaluate the safety and effectiveness of EVOLVE104 in participants with advanced urothelial and squamous cell carcinomas who have previously taken standard treatment options, have declined or have been ineligible for treatment with these medications. Participants with advanced or metastatic cancer who meet all eligibility criteria may be eligible to participate in the study.

A Study of Sigvotatug Vedotin in Advanced Solid Tumors

This trial will look at a drug called sigvotatug vedotin (SGN-B6A) alone and with pembrolizumab, with or without chemotherapy, to find out whether it is safe for people who have solid tumors. It will study sigvotatug vedotin to find out what its side effects are. A side effect is anything the drug does besides treating cancer. It will also study whether sigvotatug vedotin works to treat solid tumors. The study will have four parts. * Part A of the study will find out how much sigvotatug vedotin should be given to participants. * Part B will use the dose found in Part A to find out how safe sigvotatug vedotin is and if it works to treat solid tumors. * Part C of the study will find out how safe sigvotatug vedotin is in combination with these other drugs. * Part D will include people who have not received treatment. This part of the study will find out how safe sigvotatug vedotin is in combination with these other drugs and if these combinations work to treat solid tumors. * In Parts C and D, participants will receive sigvotatug vedotin with either: * Pembrolizumab or, * Pembrolizumab and carboplatin, or * Pembrolizumab and cisplatin.

A Study to Investigate ALE.P02 as Monotherapy in Adult Patients With Selected CLDN1+ Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, preliminary anti-tumor activity, and to determine the recommended Phase II dose (RP2D) of the ALE.P02 monotherapy in adult patients with selected squamous solid tumors.

A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B)

This is a Phase 1/2, multicenter, randomized, open-label umbrella platform study to evaluate the safety and efficacy of investigational agents with or without pembrolizumab and/or chemotherapy, for the treatment of participants with second line (2L) esophageal squamous cell carcinoma (ESCC) who have previously been exposed to PD-1/PD-L1 based treatment.

Chemoradiation and Pembrolizumab Followed by Pembrolizumab and Lenvatinib Before Surgery for the Treatment of Non-metastatic Esophageal or Esophageal/Gastroesophageal Junction Cancer

This phase II trial studies the effect of chemoradiation and pembrolizumab followed by pembrolizumab and lenvatinib before surgery in treating patients with esophageal or esophageal/gastroesophageal junction cancer that has not spread to other places in the body (non-metastatic). Pembrolizumab is an immunotherapy drug that works by harnessing the immune system to attack cancer. Lenvatinib is an anti-cancer drug that works by stopping or slowing down the growth of cancer cells. Chemotherapy drugs, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving chemoradiation and pembrolizumab followed by pembrolizumab and lenvatinib before surgery may kill more tumor cells.

Evaluation of Skin Tests in Biotherapy Allergies

Biotherapies are biological (extracted from an organism or living tissue) or biotechnological drugs used in the treatment of multiple conditions, such as autoimmune inflammatory diseases, cancers, and hematologic diseases. In recent years, these biotherapies have notably emerged in the treatment of cancers and hematologic disorders. As such, most patients with cancers or hematologic diseases will likely receive a biotherapy as part of their care pathway. These biotherapies are associated with various side effects, including hypersensitivity or allergic reactions, which are often poorly characterized in clinical trials. These reactions manifest as symptoms without specific dermatologic or allergologic semiology (such as itching, erythema, shortness of breath, sometimes digestive issues, or discomfort, and in some cases, an anaphylactic reaction). Unlike other treatments, such as antibiotics and neuromuscular blockers, there are currently no guidelines on the concentrations to use in skin tests for biotherapies. We propose conducting prospective clinical research to scientifically establish the concentrations to be used when investigating hypersensitivity to a biotherapy, in line with best practice recommendations for drug skin testing.

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.

Precision Medicine for Immunotherapy-Resistant Advanced Esophageal Cancer

This study is an open-label, biomarker-integrated umbrella trial designed to evaluate the clinical efficacy of molecular subtype- and genomic biomarker-guided precision therapies in patients with advanced esophageal cancer refractory to prior immunotherapy. Conducted in a two-step process, the study first enrolls patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have progressed on prior immunotherapy, performing circulating tumor DNA (ctDNA) sequencing to stratify them into three distinct treatment cohorts, after which patients receive tailored combination regimens matched to their specific molecular profiling in the second step. Specifically, Cohort 1 includes patients with high EGFR expression or activation of EGFR-related signaling pathways, who will receive Afatinib (40 mg, p.o., Q.D.) combined with Toripalimab (240 mg, i.v., Q21D) in a 21-day treatment cycle, continuing until radiographic disease progression (PD), unacceptable toxicity, loss to follow-up, death, or other investigator-determined criteria for discontinuation, with a maximum toripalimab treatment duration of 24 months. Cohort 2 comprises patients harboring genomic alterations directly associated with cell cycle regulation or activation of cell cycle signaling pathways, who will be treated with Dalpiciclib (125 mg, p.o., Q.D. for 21 consecutive days followed by a 7-day off period in a 28-day cycle \[Q4W\]) combined with Pyrotinib maleate (320 mg, p.o., Q.D., administered within 30 minutes post-meal, Q4W) until disease progression, unacceptable toxicity, initiation of a new anti-tumor therapy, withdrawal of consent, or investigator's decision for treatment discontinuation. Cohort 3 includes patients with other molecular profiles who do not fit Cohorts 1 or 2, who will receive Camrelizumab (200 mg, i.v., Q3W) and Apatinib (250 mg, p.o., Q.D.), with clinical efficacy evaluations performed every 6 weeks, continuing until radiographic PD, unacceptable toxicity, death, or treatment discontinuation, whichever occurs first. The study aims to recruit an estimated maximum of 90 subjects, enrolling up to 30 subjects per cohort, with the final sample size dependent on the observed toxicities and the prevalence of each molecular cohort within the screened population.

Dose Escalation Study of a PD1-LAG3 Bispecific Antibody in Patients With Advanced and/or Metastatic Solid Tumors

This is a first-in-human, open-label, multicenter, Phase I multiple-ascending dose (MAD) study of RO7247669, an anti PD-1 (programmed death-1) and LAG-3 (Lymphocyte-activation gene 3) bispecific antibody, for participants with advanced and/or metastatic solid tumors. This study aims to establish the maximum tolerated dose (MTD) and/or define the recommended phase 2 dose (RP2D) based on the safety, tolerability, pharmacokinetic (PK) and/or pharmacodynamic (PD) profile of RO7247669, and to evaluate preliminary anti-tumor activity in participants with solid tumors. An expansion part of the study is planned to enroll tumor-specific cohorts to evaluate anti-tumor activity of the MTD and/or RP2D of RO7247669 and to confirm safety and tolerability in participants with selected tumor types.

First-in-Human Study of PLX-61639 in Locally Advanced or Metastatic Solid Tumors

A multicenter, single-arm, first-in-human study to investigate the safety, pharmacokinetics, and preliminary antitumor activity of PLX-61639 in participants with locally advanced or metastatic, relapsed/refractory, SMARCA4-deficient solid tumors who are intolerant of or have failed available, approved therapies. The study will be conducted in 3 parts: dose escalation (Part 1), dose optimization (Part 2), and cohort expansion (Part 3). Each part of the study will consist of a Screening Phase lasting up to 28 days during which participants will be assessed for eligibility, a Treatment Phase beginning on Cycle 1 Day 1 and consisting of consecutive 28-day cycles, an End of Treatment Visit, and a Post-Treatment Follow-Up Phase. Participants will receive their assigned dose of PLX-61639 administered orally, once daily until progression/relapse, intolerance, death, or withdrawal from study treatment by the Investigator or participant.

Surgery vs. Radical Chemoradiotherapy for Esophageal SCC After Neoadjuvant Immunochemotherapy

This is a Phase III, multicenter, open-label, randomized controlled trial. The study aims to compare organ preservation versus esophagectomy in patients with locally advanced, resectable thoracic esophageal squamous cell carcinoma (ESCC) who achieve a complete or partial clinical response (cCR/cPR) following neoadjuvant immunochemotherapy.

Retlirafusp Alfa Plus Chemotherapy as Neoadjuvant Therapy for Thoracic ESCC

This is a prospective, single-arm, exploratory clinical study designed to evaluate the efficacy and safety of retlirafusp alfa combined with chemotherapy (nab-paclitaxel and cisplatin) as a neoadjuvant therapy for patients with resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC). The primary objective of this study is to assess the pathologic complete response (pCR) rate in the target population. A total of 33 patients with histologically or cytologically confirmed resectable locally advanced thoracic ESCC are planned to be enrolled.

A Study to Evaluate LBL-007 in Combination With Tislelizumab Plus Chemotherapy in Participants With Unresectable Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma

This is a randomized, open-label study to compare how well LBL-007 works in combination with tislelizumab and chemotherapy versus tislelizumab and chemotherapy when given as the first-line treatment in participants with inoperable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC).

Time-of-Day of Immunotherapy Infusion in Neoadjuvant Immunochemotherapy for Thoracic ESCC

This is a prospective, multi-cohort, exploratory clinical study designed to evaluate the efficacy and safety of neoadjuvant adebrelimab combined with chemotherapy in patients with resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC), with a particular focus on the effect of the time-of-day of immunotherapy infusion. Eligible patients with histologically or cytologically confirmed, resectable locally advanced thoracic ESCC will be randomly assigned in a 1:1:1 ratio to three cohorts according to predefined immunotherapy infusion time windows. Cohort A will receive adebrelimab plus chemotherapy with the first cycle initiated at or after 15:00 and subsequent cycles initiated before 15:00; Cohort B will receive all three cycles initiated before 15:00; and Cohort C will receive all three cycles initiated at or after 15:00. Neoadjuvant treatment consists of three cycles of adebrelimab in combination with nab-paclitaxel and cisplatin, followed by surgical resection 4-6 weeks after completion of neoadjuvant therapy. The primary endpoint of the study is pathological complete response (pCR). Secondary endpoints include event-free survival (EFS), major pathological response (MPR) rate, R0 resection rate, overall survival (OS), and disease-free survival (DFS). Tumor response will be assessed according to RECIST version 1.1, and pathological response will be evaluated using the College of American Pathologists (CAP) tumor regression grading system and AJCC 8th edition staging criteria. Safety will be continuously monitored throughout the study, and patients will undergo scheduled follow-up for disease progression or recurrence and survival after completion of study treatment.

an AI-Driven Four-Tier Invasion Depth Classification for Early Esophageal Cancer

The goal of this retrospective observational study is to evaluate whether preoperative endoscopic imaging can accurately assess tumor invasion depth in patients with early esophageal neoplasia undergoing endoscopic submucosal dissection (ESD). The main question it aims to answer is:"How accurately can preoperative multimodal endoscopic imaging predict histopathological invasion depth in early esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia?" If there is a comparison group: Not applicable (no intervention or arm comparison was specified; analyses are based on diagnostic performance against postoperative pathology as the reference standard). Participants will: * Be retrospectively identified from two tertiary hospitals in China; * Have pathologically confirmed early esophageal squamous cell carcinoma or high-grade intraepithelial neoplasia treated with ESD; * Have complete postoperative pathology data including invasion depth, lesion size, location, lymphovascular invasion, and margin status; * Have preoperative high-quality endoscopic images (white-light imaging, narrow-band imaging, iodine staining, and blue laser imaging); * Undergo retrospective image-pathology correlation analysis to assess diagnostic performance of invasion depth assessment.

A Phase 1/2 Trial of TER-2013 in Patients With Solid Tumors Harboring AKT/PI3K/PTEN Pathway Alterations

This is a Phase 1/2, open-label, multicenter study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of TER-2013 in patients with advanced solid tumors harboring AKT/PI3K/PTEN pathway alterations.

Study of Durvalumab Versus Placebo in Combination With Definitive Chemoradiation Therapy in Patient With ESCC

This is a Phase III, randomized, double-blind, placebo-controlled, multi-center international study to assess the efficacy and safety of durvalumab administered concurrently with dCRT in patients with locally advanced, unresectable esophageal squamous cell carcinoma (ESCC).

Safety of RAD301 in Healthy Human Volunteers and Patients With Pancreatic Cancer or Other Solid Tumors

This is a Phase 1a, open label, single dose, extended study of safety and biokinetics of RAD301 in healthy human volunteers and individuals with PDAC or Other Solid Tumors