Clinical Research Directory

STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma

Background: Immunotherapy is a type of treatment that works by making the body s own immune system stronger. These treatments are used for cancers such as non small cell lung cancer (NSCLC); thymic carcinoma (TC); or metastatic castrate-resistant prostate cancer (mCRPC). But these cancers may still come back after treatment. Objective: To test a new immunotherapy drug (STAR0602), alone or combined with an approved drug (nivolumab), in people with NSCLC, mCRPC, or TC. Eligibility: People aged 18 years or older with NSCLC, mCRPC, or TC that did not respond to treatment or returned after treatment. Design: Participants will be screened. They will have blood and urine tests. They will have imaging scans and a test of their heart function. STAR0602 and nivolumab are given through a needle inserted into a vein (infusion). Participants will be treated in 28-day cycles. They will receive infusions of 1 or both drugs on the first and 15th day of each cycle. They will remain in the hospital for up to 5 days after their first 2 infusions of STAR0602. Imaging scans, blood tests, and other tests may be repeated during study visits. Participants may opt to have tissue samples (biopsies) taken from their tumors. Some blood and tissue samples may be used for genetic tests. Participants may continue getting STAR0602 for up to 2 years and nivolumab for up to 6 months. Participants will have an end-of-study visit within 1 month, and follow-up phone calls 1 month and 3 months, after they stop the study drug. Long-term follow-up calls and visits will continue every 3 to 6 months for up to 5 years.

Effects of a Visual Interactive LINE Chatbot on Self-Management of EGFR-TKI Related Side Effects in Patients With Lung Cancer

This study aims to evaluate a visual interactive LINE chatbot designed to support self-management of treatment-related side effects among patients with advanced lung cancer receiving epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Patients receiving EGFR-TKI treatment often experience long-term side effects that require ongoing self-management. In this randomized controlled trial, participants will be assigned to receive either usual care alone or usual care plus access to the LINE chatbot intervention, which provides visualized and interactive educational content for symptom monitoring and self-care. The primary outcome of this study is self-management ability related to EGFR-TKI-associated side effects. Secondary outcomes include quality of life during treatment and overall satisfaction with the LINE chatbot intervention.

A Study to Investigate the Safety and Efficacy of KQB368 as Monotherapy in Participants With Advanced Solid Malignancies

The goal of this study is to learn if KQB368 works to treat advanced solid malignancies in adults. The study will also learn about the safety of KQB368. The main questions the study aims to answer are: * What is the safe dose of KQB368 as a monotherapy? * Does KQB368 decrease the size of the tumor? * What happens to KQB368 in the body? Participants will: * Take KQB368 orally daily in 21-day cycles * Return to the study site about 7 times in the first 5 weeks, and then once at the beginning of every 21-day cycle after that

A Phase 2 Platform Study of Immunomodulatory Compounds in ICI-refractory Non-small Cell Lung Cancer

To learn if SAR445877 can help to control locally advanced or metastatic NSCLC in patients who have previously received ICI therapy.

A Phase 1 Study of IM-1617 in Participants With Advanced Cancer

This study will test the safety and effectiveness of a drug called IM-1617 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). This study will have two parts. Part A will test increasing doses of IM-1617 to find out the safe dose and schedule of IM-1617 for participants. Part B will use the dose and schedule found in Part A to further study the safety of IM-1617 and if it works to treat solid tumor cancers.

Evaluation of a Cancer Lysate Vaccine and Montanide (Registered Trademark) ISA-51 VG With or Without the IL-15 Super-Agonist N-803 as Adjuvant Therapy for PD-L1 Negative Non-Small Cell Lung Cancer

Background: Surgery is the primary treatment for non-small cell lung cancer (NSCLC) that is diagnosed in its earlier stages. But the tumors often return. Radiation and chemotherapy can improve survival in some people who have had surgery for NSCLC, but these treatments also cause serious side effects. A new approach, called immunotherapy, may be a better way to stop NSCLC tumors from coming back. Objective: To test a new treatment (H1299 lung cancer cell vaccine combined with the drug N-803) in people who received surgery for NSCLC. Eligibility: Adults aged 18 years or older with no sign of disease after surgery for NSCLC. Design: Participants will be screened. They will have a physical exam with blood tests. They will have tests of their heart and lung function. They will have imaging scans. Study treatment will be given in 28-day cycles. Participants will visit the clinic on the first day of each cycle. They will receive 2 treatments at each visit: The study vaccine is given as 2-4 small shots under the skin of the thigh or arm. N-803 is given as a shot under the skin of the abdomen. Treatment will continue for 6 cycles. Blood tests and imaging scans will be repeated throughout the study. Participants will have a blood test 1 month after receiving the 6th vaccine. Some participants may then resume taking N-803; they may also receive 2 more vaccinations at 3 and 6 months after their previous treatment. Follow-up visits will continue for up to 5 years.

A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC)

This study will evaluate the efficacy and safety of multiple therapies in participants with locally advanced, unresectable, Stage III NSCLC with eligible biomarker status as determined by Version 8 of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) NSCLC staging system.

A Phase 1 Trial of KAN-001 With Pembrolizumab, With or Without Chemotherapy, in Participants With PD-L1-Positive Non-Small Cell Lung Cancer

The goal of this Phase 1 clinical trial is to learn whether KAN-001, an investigational live biotherapeutic product, can be safely given with pembrolizumab, with or without chemotherapy, to adults with PD-L1-positive, inoperable or metastatic non-small cell lung cancer. The main questions it aims to answer are: * What side effects occur when KAN-001 is given with pembrolizumab, with or without chemotherapy? * Can the microbial strains contained in KAN-001 be detected in participants' stool after treatment? Participants will: * Complete a bowel preparation before receiving the first dose of KAN-001. * Take a loading dose of KAN-001, followed by maintenance doses every 3 weeks. * Receive pembrolizumab every 3 weeks. Some participants will also receive chemotherapy. * Provide blood, stool, and stool-wipe samples and complete a gastrointestinal symptom diary. * Undergo imaging scans and other study assessments to monitor their cancer, health, and safety.

Risk-Adapted Segmental Esophagus-Sparing Radiotherapy for Definitive Non-Small Cell Lung Cancer

This is a multicenter, open-label, randomized, phase 3 superiority trial. The purpose is to find out whether a risk-adapted segmental esophagus-sparing radiotherapy plan is better than a standard radiotherapy plan at reducing moderate or worse acute radiation esophagitis in adults with locally advanced non-small cell lung cancer (NSCLC) who are receiving definitive concurrent or sequential chemoradiotherapy, with or without immunotherapy. Acute radiation esophagitis is inflammation of the esophagus caused by radiation; it can cause swallowing pain or difficulty and may interrupt treatment. The study will also check whether the esophagus-sparing plan affects tumor control, survival, other side effects, and quality of life. About 140 participants will be randomly assigned 1:1 to the esophagus-sparing plan or the standard plan. Randomization will be stratified by study center, concurrent versus sequential chemoradiotherapy, ECOG performance status, and PD-L1 expression. In the esophagus-sparing group, the radiotherapy plan sets graded average dose limits to parts of the esophagus near the tumor target, based on how much the target overlaps the esophagus. The standard group receives routine intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) without active esophagus avoidance. Both groups receive the same radiotherapy dose (60-66 Gy in 30-33 fractions) and the same chemotherapy/immunotherapy chosen by their doctors. The study is open-label, so participants and doctors will know which radiotherapy plan is used; the main statistical analysis will be blinded to group assignment. The main measure is the proportion of participants with Grade 2 or higher acute radiation esophagitis within 3 months after starting radiotherapy, graded by CTCAE v5.0. Participants will be followed for up to 24 months after randomization. This study does not test a new drug or device.

Osimertinib Plus Stereotactic Radiosurgery/Radiotherapy for EGFR-Mutant Non-Small Cell Lung Cancer With Symptomatic Brain Metastases

The goal of this clinical trial is to learn whether adding stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT), delivered on a linear accelerator (LINAC), to osimertinib improves control of brain metastases in adults with stage IV non-small cell lung cancer (NSCLC) carrying a sensitizing EGFR mutation (exon 19 deletion or exon 21 L858R) whose brain metastases cause neurological symptoms (present at diagnosis or arising during osimertinib treatment). The main questions it aims to answer are: * What proportion of participants achieve an intracranial objective response (complete or partial response by RANO-BM criteria)? * How long do participants live without intracranial or overall disease progression, how long do they live overall, and what side effects occur with the combined treatment? Participants will: * Take osimertinib 80 mg by mouth once daily (or continue it if they have already started it). * Receive SRS (1 fraction) or SRT (3 or 5 fractions) to all brain metastases (1 to 4 lesions, each 4 cm or smaller) at Cho Ray Hospital, Ho Chi Minh City, Vietnam. * Have brain MRI (or contrast-enhanced CT if MRI is not possible) and chest-abdomen CT every 12 weeks, monthly clinic visits to check for side effects, and blood tests, ECG and echocardiography every 12 weeks.

Cabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer and Those With Other Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity

The purpose of this phase II study is to find out what effects cabozantinib (XL184) has, good and/or bad, in patients whose tumors one of the following gene changes RET, ROS1, or NTRK fusion, or increased MET or AXL activity. A phase II study looks at how effective a medication is at treating a specific type of cancer and collects information on the side effects of the study treatment. RET, ROS1, or NTRK fusion or increased MET or AXL activity gene leads to lung cancer cell growth. Cabozantinib is an oral medicine that inhibits of RET, ROS1, NTRK, MET, and AXL. In addition, this drug interferes with other cell pathways that also cause cancer cells to grow, form new blood vessels, and spread to other organs of the body. The goal of using cabozantinib is to shrink the cancer and to prevent it from growing Cabozantinib has been studied and shown to cause cancer shrinkage in other cancers such as medullary thyroid cancer and prostate cancer. We thus have a good idea of what side-effects it causes and can anticipate them.

PET/CT-Based Intratumoral Heterogeneity and Multimodal Imaging for Tumor Diagnosis and Prognosis

Background \& Rationale: Intratumoral heterogeneity (ITH) is a recognized hallmark and critical driver of therapeutic resistance, rapid disease progression, and poor survival across solid malignancies, notably advanced non-small-cell lung cancer (NSCLC). While tissue biopsies provide histopathologic confirmation, they are invasive and subject to severe spatial sampling bias. Standard whole-tumor radiomics from single-modality CT often masks localized subregional ecological niches. 18F-FDG PET/CT unites glucose metabolic activity with anatomical resolution, offering an ideal non-invasive tool to map whole-tumor spatial and functional heterogeneity in vivo. Methods \& Design: In this multicenter, bidirectional (retrospective and prospective) observational cohort study, 900 advanced NSCLC patients receiving first-line systemic therapies (chemotherapy, anti-PD-1 immunotherapy, and EGFR-TKIs) were enrolled. Baseline 18F-FDG PET/CT scans obtained within 2 weeks prior to therapy were partitioned into distinct biological habitats using entropy-intensity clustering. IBSI-compliant radiomic features were extracted to develop treatment-specific imaging intratumoral heterogeneity (IITH) signatures. Diagnostic accuracy for staging/metastases and prognostic performance for 6-month progression status, progression-free survival (PFS), and overall survival (OS) were comprehensively validated across internal, external multicenter, and independent prospective cohorts, with biological explainability benchmarked against digital histopathology (HoVer-Net nuclear morphometrics) and transcriptomics.

A Study of Mobocertinib in Japanese Adults With Non-Small Cell Lung Cancer

This study is in 2 parts. Different participants will take part in the 1st and 2nd parts of the study. The main aim of the 1st part of the study is to check how much Mobocertinib adults with non-small cell lung cancer (NSCLC) can receive without getting side effects from it. The main aim of the 2nd part of the study is to learn if the condition of adults with non-small cell lung cancer improves after treatment with Mobocertinib. Another aim is to continue checking for side effects from Mobocertinib. In the 1st part of the study, at the first visit, the study doctor will check who can take part. For those that can take part, participants will take a capsule of Mobocertinib once a day for 28 days. This will count as 1 cycle. Different small groups of participants will receive lower to higher doses of Mobocertinib. The study doctors will check for side effects after each dose of TAK 788. In this way, researchers can work out the best dose of Mobocertinib to give participants in the 2nd part of the study. Participants will visit the clinic 30 days after their treatment has finished for a final check-up. In the 2nd part of the study, at the first visit, the study doctor will check who can take part. Participants will receive the best dose of Mobocertinib worked out from the 1st part of the study. Participants will receive Mobocertinib in the same way as those from the 1st part of the study. The study doctors will learn if the condition of these participants improves after treatment with Mobocertinib. The study doctors will also check for side effects from Mobocertinib. After treatment has finished, participants will visit the clinic every 12 weeks until the end of the study. In both parts of the study, participants can receive Mobocertinib for up to just over 1 year, or longer if their condition stays improved.

Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer

Background: A person s tumor is studied for mutations. When cells are found that can attack the mutation in a person s tumor, the genes from those cells are studied to find the parts that make the attack possible. White blood cells are then taken from the person s body, and the gene transfer occurs in a laboratory. A type of virus is used to transfer the genes that make those white blood cells able to attack the mutation in the tumor. The gene transfer therapy is the return of those white blood cells back to the person. Objective: To see if gene transfer therapy of white blood cells can shrink tumors. Eligibility: People with certain metastatic cancer for which standard treatments have not worked. Design: Participants may complete screening under another protocol. Screening includes: * Getting tumor cells from a previous procedure * Medical history * Physical exam * Scans * Blood, urine, heart, and lung tests The study has 8 stages: 1. Screening tests repeated over 1-2 weeks. Participants will have leukapheresis: Blood is removed by a needle in one arm. A machine removes white blood cells. The rest of the blood is returned by a needle in the other arm. 2. Care at home over approximately 12 weeks. 3. Stopping therapy for 4-6 weeks while their cells are changed in a lab. 4. Hospital stay approximately 3-4 weeks for treatment. An IV catheter will be placed in the chest to administer drugs. 5. Patients on Arm 2 of the study will receive the first dose of pembrolizumab while in the hospital. Three additional doses will be given after the cell infusion 3 weeks apart. 6. Receiving changed cells by catheter. Then getting a drug over 1-5 days to help the cells live longer. 7. Recover in the hospital for 1-2 weeks. Participants will get drugs and have blood and urine tests. 8. Participants will take an antibiotic and maybe an antiviral for at least 6 months after treatment. They will have repeat screening tests at visits every few months for the first year, every 6 months for the second year, then as determined.

First-In-Human Study of STX-721/PFL-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR or HER2 Exon 20 Insertion Mutations

Study STX-721-101/PFL-721CI101 is an open label, Phase 1/2 study evaluating the safety, tolerability, pharmacokinetic (PK) exposure, and preliminary antitumor activity of STX-721/PFL-721 in participants with non-small cell lung cancer (NSCLC) carrying EGFR or HER2 exon 20 insertion (ex20ins) mutations.

A Phase 1 Study of LNCB74 in Advanced Solid Tumors

This is an open-label, phase 1, dose escalation and dose expansion study to determine safety and tolerability, and to determine the maximum tolerated dose and / or recommended phase 2 dose of LNCB74 in participants with advanced solid tumors.

Beamion LUNG-1: A Study to Test Different Doses of Zongertinib in People With Different Types of Advanced Cancer (Solid Tumours With Changes in the HER2 Gene)

The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumours with changes in the HER2 gene) for whom previous treatment was not successful. The second part is open to people with non-small cell lung cancer with a specific mutation in the HER2 gene. The purpose of the first study part is to find the highest dose of a medicine called zongertinib the participants can tolerate. Once this dose is found, it will be used in the second study part to test whether zongertinib can make tumours shrink. In this study, zongertinib is given to people for the first time. Participants take zongertinib as tablets once a day or twice a day. The participants are in the study for as long as they benefit from and can tolerate treatment. Study doctors regularly check the participants' health and monitor the tumours. The doctors also take note of any unwanted effects that could have been caused by zongertinib.

Phase III, Open-label, Study of First-line Dato-DXd in Combination With Rilvegostomig for Advanced Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations

The purpose of this study is to evaluate efficacy and safety of Dato-DXd in combination with rilvegostomig or rilvegostomig monotherapy compared with pembrolizumab monotherapy as a first line therapy in participants with locally advanced or metastatic non-squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.

A Clinical Study to Assess the Efficacy of Adjuvant Immunotherapy With Cemiplimab in Patients With Surgically Removed Non-small Cell Lung Cancer Who Have Not Received Prior Chemotherapy

ARCH is a randomised, stratified, multicentre, phase III trial. Protocol treatment consists of cemiplimab, 350 mg i.v., every 3 weeks, for 4 cycles, followed by 700 mg i.v., every 6 weeks for 6 cycles or until relapse or unacceptable toxicities, whichever occurs first. The primary objective of the study is to determine the efficacy of adjuvant cemiplimab, as measured by disease-free survival, in patients without prior adjuvant platinum-based chemotherapy, compared to observation without adjuvant treatment. The primary objective will be assessed in patients with tumours with centrally confirmed PD-L1 expression of ≥1%.

Efficacy and Safety of Almonertinib Combined With Recombinant Human Endostatin in the Treatment of Stage IIIB-IV Non-small Cell Lung Cancer

Rationale: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer in the world, and patients with stage IIIB-IV have a poor prognosis. EGFR mutations, especially the 19th amino acid deletion (19del) and the 21st amino acid L858R mutation, are the most common types of gene mutations in NSCLC. These mutations usually lead to overactivity of EGFR, thereby stimulating excessive proliferation of lung cancer cells. At present, the conventional treatment for such patients is mainly the use of EGFR tyrosine kinase inhibitors (EGFR-TKIs) for treatment. However, although EGFR-TKIs have achieved certain results in the treatment of NSCLC patients with EGFR mutations, their treatment effects are often difficult to sustain due to the resistance of patients to these drugs. Therefore, finding new treatment strategies to improve the survival rate and quality of life of such patients is an important current research direction. The results of many studies suggest that EGFR TKIs and anti-angiogenic drugs can inhibit tumors from different signaling pathways. EGFR-TKIs can inhibit the epidermal growth factor receptor pathway and inhibit tumor growth; anti-angiogenic drugs inhibit tumor angiogenesis by binding to vascular endothelial growth factor (VEGF). At the same time, the combination of the two has a synergistic effect. Both EGFR and VEGFR-2 signaling pathways can trigger downstream signaling pathways such as PI3K/AKT and RAS/RAF/ERK, affecting cell proliferation. EGFR activation can also drive HIF-1α upregulation, leading to VEGF gene expression. Many clinical studies have confirmed that the A+T treatment model can improve the efficacy of EGFR-positive NSCLC. Methods: This study is planned to adopt a mixed design. We will prospectively collect new patient data and retrospectively analyze existing patient data. In the prospective part, we will treat patients with stage IIIB-IV NSCLC with EGFR amino acid 21 L858R mutation and amino acid 19 deletion (19del) with a combination of ametinib mesylate (AUMOLERTINIB) and recombinant human endostatin (ENDOSTAR). In the retrospective part, we will extract the existing data of patients treated with AUMOLERTINIB alone from the hospital\'s electronic medical record system as a control group. The primary endpoint is progression free survival (PFS). Secondary endpoints are objective response rate (ORR), duration of response (DoR), adverse events (AE), quality of life (EORTCQLQ-L13) score, anxiety and depression self-rating scale (HADS) and patient health questionnaire-9 (PHQ-9). Route: In the prospective part, we will perform genetic testing on patients to determine their EGFR mutation status. Then, we will treat patients with stage IIIB-IV NSCLC with EGFR amino acid 21 L858R mutation and amino acid 19 deletion with ametinib mesylate and recombinant human endostatin, and match the corresponding data in the hospital database. We will regularly follow up patients participating in the prospective study, collect data on their disease progression and survival, and perform statistical analysis on these data to evaluate the effectiveness and safety of the combination therapy. Expected: We expect that the combination of ametinib mesylate and recombinant human endostatin can improve the survival rate and quality of life of patients with stage IIIB-IV NSCLC with EGFR amino acid 21 L858R mutation and amino acid 19 deletion. This is mainly because ametinib mesylate and recombinant human endostatin target EGFR hyperactivity and angiogenesis, two processes that play a key role in the development of NSCLC, respectively, so their combined use may produce a synergistic effect, thereby improving the therapeutic effect.

A Phase I Study of HS-20093 Injection in Combination Therapy in Non-Small Cell Lung Cancer

This is a multicenter, open-label, Phase 1 clinical study to evaluate the efficacy and safety of HS-20093 combination therapy in subjects with advanced or metastatic non-small cell lung cancer without actionable genomic alterations.

Study of Izalontamab Brengitecan (BMS-986507) in Combination With Osimertinib Versus Osimertinib Monotherapy or Osimertinib in Combination With Platinum-based Chemotherapy for EGFRmt Non-small Cell Lung Cancer (IZABRIGHT-Lung02)

The purpose of this study is to evaluate izalontamab brengitecan (iza-bren) combined with osimertinib in participants with previously untreated, locally advanced or metastatic EGFR-mutant NSCLC, compared to osimertinib alone or osimertinib combined with platinum-based chemotherapy

Predicting Response to Anti-PD-1/PD-L1 Immunotherapy by Plasma Extracellular Vesicle Analysis

The objective of this prospective multicenter study is to evaluate whether the analysis of immunological biomarkers present in circulating extracellular vesicles is associated with the response to anti-PD-1/PD-L1 treatments in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) or unresectable melanoma. Patients will receive standard-of-care treatment and will be followed according to routine clinical practice. The study involves the collection of four study-specific blood samples at different time points during follow-up, as well as the collection of standard immunohistochemistry results, thoraco-abdomino-pelvic CT scans, and tumor DNA genotyping analyses performed as part of routine care. The study aims to determine: * whether baseline biomarkers in extracellular vesicles are associated with response to anti-PD-1/PD-L1 treatment, * how these biomarkers change over the course of treatment, and * to provide exploratory data for the development of predictive immunological response signatures.

Biospecimen Procurement for Center for Immuno-Oncology Immunotherapy Protocols

Background: Cancer has a major impact in the United States and across the world. In 2015, over 1.5 million new cases of cancer were diagnosed in the U.S. Researchers want to study samples from people with cancer or a pre-malignant condition. They hope to develop more effective treatments. Objective: To better understand the biology of malignancies and why certain cancers respond differently to treatment. Eligibility: Adults at least 18 years old with cancer or a pre-cancerous condition. Design: Participants will be screened with a medical history, physical exam, and blood tests. Their diagnosis will be confirmed by the NCI Laboratory of Pathology. Participants will send tissue blocks or slides from their original tumor biopsy. At least once, participants will have a medical history, physical exam, and blood and urine tests. Participants may have the following tests. They may have them more than once: Apheresis. A needle in one arm removes blood. Blood is run through a machine and the sample cells are taken out. The rest of the blood is returned by a needle in the other arm. Bone marrow aspiration and biopsy. The hipbone will be numbed. A needle will be put into the hipbone. Bone marrow will be taken out through the needle. Piece of cancer tissue taken by a needle and syringe. Computed tomography (CT) scan, magnetic resonance imaging (MRI) and/or positron emission tomography (PET) scan or ultrasound to help locate their tumor. For the scans, they lie in a machine that takes pictures. A small piece of skin removed. Participants will be contacted by phone once a year to find out how they are doing.