New Haven

Researchers are studying HPV-associated head and neck squamous cell carcinoma that can be surgically removed. They aim to find out if combining the chemotherapy drug 5-azacytidine with the immunotherapy drug nivolumab improves the immune system's ability to fight this cancer compared to using either drug alone. This Phase 2 trial focuses on the immune-related response of the tumor to these treatments before surgery. Participants are randomly assigned to one of three groups: 5-azacytidine alone, nivolumab alone, or both drugs combined. 5-azacytidine is given intravenously for five days, while nivolumab is given on specific days depending on the group. Surgery is scheduled shortly after treatment, between days 16 and 18. The study plans to enroll a total of 48 patients to compare immune responses between the combination therapy and the individual drugs. During the study, patients undergo biopsies and other evaluations to measure immune response in the tumor, changes in tumor cell activity, and overall treatment effects. Researchers will monitor side effects and tumor changes using specific laboratory and imaging tests. The main outcome is the immune-related pathologic response after treatment, assessed during surgery, with additional measures of tumor immune cell infiltration and other markers to understand the treatments’ impact.

Researchers are evaluating a new treatment called ifinatamab deruxtecan (I-DXd) for men with metastatic castration-resistant prostate cancer (mCRPC). This study compares I-DXd to chemotherapy to see if it helps people live longer overall and live longer without their cancer worsening. It is a Phase 3, open-label trial focused on patients who have progressed on prior therapies and have evidence of metastatic disease. Participants receive either I-DXd through an intravenous infusion every 3 weeks or docetaxel chemotherapy administered every 3 weeks. Prednisone tablets are also given daily as part of the treatment plan. Before each I-DXd dose, premedication is provided to help prevent nausea and vomiting using a combination of drugs such as corticosteroids and anti-nausea medicines. Treatment continues until disease progression, unacceptable side effects, or other reasons to stop. During the study, researchers monitor overall survival and how long patients live without their cancer progressing, for up to about 36 months. Participants undergo tumor tissue collection, scans, and assessments to track disease status and side effects. Safety is closely watched throughout treatment. The study includes men aged 18 and older with confirmed prostate cancer and metastatic disease who have previously received certain hormone therapies but no prior taxane chemotherapy for mCRPC.

Researchers are studying a treatment called MK-2214 to see if it can slow certain brain changes in people with early Alzheimer's disease (AD). AD is a form of dementia that causes memory loss, difficulties with communication, and challenges in decision-making, which affect daily activities. The study aims to find out if MK-2214 can slow the spread of tau protein in the brain compared to a placebo and to assess the safety and tolerability of MK-2214. Participants will receive either MK-2214 or a placebo through an intravenous (IV) infusion. The study is designed as a phase 2, randomized, placebo-controlled, double-blind trial with parallel groups. The treatment period lasts up to about 23 months, during which participants will receive infusions as scheduled. The placebo looks like the study treatment but contains no active drug, helping researchers understand the treatment's effects. Throughout the study, participants will be monitored for changes in tau protein levels in the brain using PET scans and for any adverse events or side effects. Researchers will track the number of participants experiencing adverse events and those who stop treatment because of them, with safety follow-up lasting up to approximately 26 months. Participants will also undergo brain imaging such as CT, PET, or MRI scans. The study involves regular assessments to measure the treatment's impact and ensure participant safety over the study duration.

This study is a multicenter, open-label, phase I/II study of YL205 in China to evaluate the safety, tolerability, PK characteristics and preliminary efficacy of YL205 in the following selected patients with advanced solid tumors.

Researchers are evaluating the safety and effectiveness of new treatments called BNT314 and BNT327 combined with chemotherapy for people with metastatic colorectal cancer (mCRC) that is microsatellite stable or mismatch repair proficient (MSS/pMMR). This study includes participants who did not respond well to their first chemotherapy treatment and aims to find the right dose and assess how well these treatments work together to shrink tumors or slow their growth. The study includes multiple phases to test safety, dosing, and treatment benefits. The study has three parts: Part A focuses on safety and dose escalation of BNT314 with BNT327; Part B tests the safety and optimal dose of BNT314 combined with BNT327 and standard chemotherapy; and Part C compares the combination treatment with standard chemotherapy alone to see if it improves outcomes. Treatments are given by intravenous infusion or oral methods depending on the drug. Participants receive treatment until their disease worsens, they cannot tolerate the therapy, or the study ends, with an average treatment duration of 6 to 10 months. Participants will be screened, treated, and followed up for safety and long-term survival. Researchers will regularly monitor for side effects, treatment response, and disease progression using scans and laboratory tests. The study includes a safety follow-up period and a long-term survival follow-up that can last up to 57 months, with committees overseeing participant safety throughout the trial.

Researchers are evaluating the safety, effectiveness, best dose, and how the body processes (pharmacokinetics) an investigational drug called BNT326. This study includes people with advanced solid tumors that are metastatic, recurrent, or have progressed after previous treatments. The investigation is divided into two parts: Part 1 tests BNT326 alone, and Part 2 studies BNT326 alone or combined with other immunotherapy drugs, including pumitamig (BNT327). Participants have specific tumor types like melanoma, non-small cell lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer, among others. In Part 1, participants receive BNT326 by intravenous infusion in various groups based on cancer type and prior treatments. Part 2 involves BNT326 given alone or with pumitamig, also by intravenous infusion, in several defined cancer groups. Some groups are randomized to receive different dose levels or combinations to find the optimal treatment plan. The study includes a screening phase, treatment phase lasting up to 24 months or until progression or unacceptable side effects, a safety follow-up, efficacy follow-up, and long-term survival monitoring, totaling about 38 months for Part 1 and 48 months for Part 2. During the study, participants undergo regular assessments including measuring tumor response using RECIST criteria, monitoring for side effects and serious adverse events up to months after treatment ends, and measuring drug levels in the blood. Researchers track treatment interruptions or discontinuations due to side effects and evaluate dose-limiting toxicities. Tumor tissue samples are required before enrollment. Safety and effectiveness data are collected throughout treatment and follow-up periods to understand how well BNT326 works alone or combined and its safety profile.

Researchers are studying TD001, an antibody-drug conjugate (ADC) that targets prostate-specific membrane antigen (PSMA), to evaluate its safety, tolerability, drug levels, and early anti-cancer effects in men with metastatic PSMA-expressing castration-resistant prostate cancer (CRPC). This first-in-human, open-label, multicenter Phase 1/2 trial includes a dose escalation phase to find recommended doses for Phase 2, followed by an expansion phase to further assess the treatment. Participants will receive TD001 through intravenous infusions at doses and schedules defined by the study protocol. Treatment continues until the disease progresses or another reason requires stopping. Multiple dosing schedules may be explored to optimize dose and administration for effectiveness and safety in this patient group. During the study, men will have their disease monitored through measurements of tumor lesions and prostate-specific antigen (PSA) levels. Safety is carefully tracked by recording any adverse events or serious side effects, as well as any treatment modifications or discontinuations due to side effects. The study also evaluates the maximum tolerated dose and recommended Phase 2 doses over estimated follow-up periods of 9 to 21 months to guide future research.

Researchers are evaluating the safety, tolerability, and therapeutic effects of a combination treatment using BNT113 and pembrolizumab compared to pembrolizumab alone for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is positive for human papillomavirus 16 (HPV16+) and expresses the PD-L1 protein with a combined positive score of 1 or higher. This Phase II/III trial includes patients whose cancer cannot be treated with local therapies and who have not received prior systemic anticancer therapy for their current disease condition. The trial consists of two parts. Part A is a non-randomized Safety Run-In Phase to confirm the safety and tolerability of BNT113 combined with pembrolizumab at the selected dose. Part B is a randomized phase that compares BNT113 plus pembrolizumab against pembrolizumab alone as first-line treatment. Patients in Part A continue their treatment without randomization. Treatments are given by intravenous injection or infusion, and patients may receive either combination therapy or monotherapy for up to 24 months. There is also an optional pre-screening phase to test tumor samples for HPV16 DNA and PD-L1 expression before entering the main trial. Participants undergo regular assessments including tumor measurements based on RECIST 1.1 criteria confirmed by independent review. Researchers monitor treatment-emergent adverse events for up to 27 months in Part A and evaluate overall survival and progression-free survival for up to 48 months in Part B. Tumor tissue samples are collected before treatment to confirm eligibility. The study involves ongoing safety monitoring and efficacy evaluations throughout the treatment and follow-up periods.

Researchers are evaluating the safety and effectiveness of trontinemab in people aged 50 to 90 with early symptoms of Alzheimer's disease, ranging from mild cognitive impairment to mild dementia. This Phase III clinical trial focuses on those who show evidence of Alzheimer's pathology and have a recent history of cognitive decline. The study aims to measure changes in cognitive function over 72 weeks. Participants will be randomly assigned to receive either intravenous trontinemab or a placebo. The trial is designed as a double-blind, placebo-controlled study, meaning neither participants nor researchers know who receives the active drug or placebo. The treatment period lasts up to 72 weeks, during which participants will undergo various assessments to monitor their cognitive status and safety. During the study, participants will complete clinical tests including cognitive assessments and imaging such as MRI, PET scans, or cerebrospinal fluid analysis to confirm Alzheimer's pathology. A study partner will assist participants as needed. Researchers will track changes from the start of the study through week 72 using tools like the Clinical Dementia Rating. Safety monitoring and adherence to study procedures will also be closely observed throughout the trial.

This research aims to learn about the safety and dosing of COM503, a drug being studied alone or combined with zimberelimab, in people with advanced solid tumors. It is a first-in-human Phase 1 clinical trial focused on participants with advanced or recurrent metastatic solid malignancies who have progressed despite standard treatments. The study seeks to assess safety, tolerability, and determine the best doses for future research. Participants will receive COM503 either alone or together with zimberelimab through intravenous infusions. The trial has two parts: dose escalation to find the maximum tolerated or administered dose, and dose expansion to further evaluate safety and dosing at identified levels. Both treatments are given as infusions, and the study monitors how well participants tolerate these therapies. During the study, participants will have their tumors measured by CT or MRI scans and will be closely monitored for safety from the first dose until 90 days after the last dose or start of a new cancer therapy. Researchers will evaluate side effects, tolerability, and other safety outcomes. Participation involves regular assessments and follow-up to understand the effects of COM503 alone or with zimberelimab in advanced cancer settings.