New Haven

Researchers are evaluating the effects of 5-azacytidine and nivolumab, alone or combined, on HPV-associated head and neck squamous cell carcinoma that can be surgically removed. This Phase 2 trial aims to see if adding 5-azacytidine can make the cancer more responsive to treatment with nivolumab by boosting the immune systems attack on the tumor. The study focuses on patients with specific stages of oropharynx cancer confirmed to be HPV-related and involves measuring immune-related responses in the tumor tissue. Participants are randomly assigned to one of three groups 5-azacytidine alone, nivolumab alone, or both drugs combined. 5-azacytidine is given intravenously once daily for five days starting on a Monday, with anti-nausea premedication. Nivolumab is administered intravenously twice, either on days 1 and 15 for the nivolumab group or days 2 and 16 for the combination group. Surgery is scheduled shortly after treatment, between days 16 and 18 for the monotherapy groups and days 17 to 18 for the combination group. During the study, patients undergo biopsies before and after treatment to assess tumor response and immune activity. Researchers measure immune-related pathologic response, tumor infiltration by immune cells, tumor size changes, and treatment toxicity. Safety is monitored from the first treatment through 30 days after surgery. Participants provide informed consent and must meet specific health criteria to join. The total involvement includes treatment, surgery, and follow-up assessments to evaluate the treatment effects.

Researchers are evaluating a new medicine called ifinatamab deruxtecan I-DXd for treating men with metastatic castration-resistant prostate cancer mCRPC. The study aims to find out if people receiving I-DXd live longer overall and have longer periods without cancer growth or spread compared to those receiving chemotherapy. This is a Phase 3, open-label trial sponsored by Merck Sharp Dohme LLC. Participants in the study will be randomly assigned to receive either I-DXd at a dose of 12 mgkg every 3 weeks or a combination of docetaxel chemotherapy 75 mgm every 3 weeks with daily prednisone. I-DXd is given by intravenous infusion every 3 weeks until the disease progresses or side effects prevent continued treatment. Premedication is given before I-DXd to help prevent nausea and vomiting. During the study, participants will be closely monitored for overall survival and radiographic progression-free survival for up to about 36 months. Researchers will also assess several other outcomes including response rates, time to progression, pain progression, prostate-specific antigen changes, and side effects. Safety and treatment tolerability will be tracked throughout, and participants health will be regularly evaluated with scans and other tests.

Researchers are evaluating MK-2214, a study treatment designed to slow certain brain changes in people with early Alzheimers disease AD, a condition that causes memory loss, speech difficulties, and problems with decision-making. 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 treatments safety and tolerability. Tau is a protein that builds up in AD and damages brain cells, impacting daily functioning. Participants will be randomly assigned to receive either MK-2214 or a placebo through intravenous IV infusions every 4 weeks during the study period. The study uses a quadruple-blind design, meaning that participants, care providers, researchers, and those assessing outcomes will not know which treatment is given. This phase 2 trial is planned to last up to approximately 23 months for treatment and assessment. During the study, participants will undergo brain scans including tau PET imaging and assessments of cognitive and daily living abilities at regular intervals. Researchers will monitor changes in tau protein levels, cognitive scores such as the Clinical Dementia Rating-Sum of Boxes CDR-SB, and safety outcomes including adverse events and treatment discontinuations. The total study duration includes up to about 26 months of follow-up to evaluate safety and effectiveness.

Researchers are evaluating new treatments for relapsed high-grade serous ovarian cancer, a fast-growing cancer that starts in the cells covering the ovaries, lining of the belly, or fallopian tubes. This cancer has returned after prior treatment, and the study aims to understand how well the antibody drug conjugate raludotatug deruxtecan R-DXd works when combined with other anticancer agents. The study is a Phase 1b2 trial designed to assess the safety and effectiveness of these combinations in patients who have relapsed after platinum-based chemotherapy. The study has two parts Part 1 tests increasing doses of R-DXd combined with chemotherapy drugs carboplatin or paclitaxel, or with bevacizumab and pembrolizumab, to find the safest and most effective dose. Part 2 uses the recommended dose from Part 1 to further evaluate these combinations. Treatment cycles occur every 3 weeks, with up to six cycles of chemotherapy drugs and up to 35 cycles of pembrolizumab. Participants continue receiving R-DXd until their disease progresses or treatment is stopped. Participants will undergo regular assessments including scans to measure tumor response, monitoring for side effects, and evaluations of overall health. The main outcomes are safety measures like dose-limiting toxicities and adverse events, as well as how many participants experience shrinkage or disappearance of tumors. The study may last up to about three years, with ongoing monitoring of treatment effects and safety throughout the trial period.

Researchers are evaluating YL205, a drug given by intravenous infusion, in patients with advanced solid tumors. This multicenter, open-label phase III study in China aims to assess the safety, tolerability, pharmacokinetics how the drug moves through the body, and preliminary effectiveness of YL205. Eligible patients have advanced solid tumors that overexpress Napi2B and include cancers such as ovarian, non-squamous non-small cell lung, renal cell, and endometrial cancer. Participants receive YL205 as a lyophilized powder reconstituted for intravenous infusion at a dose of 160 mg per vial. Treatment is given once every three weeks in cycles, with dose levels adjusted during different study phases dose escalation phase Ia, dose expansion phase Ib, and cohort expansion phase II. The study evaluates at least two dose levels and the recommended phase 2 dose RP2D. Throughout approximately 36 months, participants are closely monitored for dose-limiting toxicities, treatment-emergent adverse events, and serious adverse events. Researchers assess tumor response using RECIST v1.1 criteria, including overall response rate, disease control rate, duration and depth of response, progression-free survival, and overall survival. Pharmacokinetic parameters like AUC, Cmax, and half-life are also measured. Patients undergo tumor sampling and radiological evaluations to track treatment effects and safety.

Researchers are evaluating a new treatment called BNT314 combined with another investigational drug, BNT327, and chemotherapy for people with metastatic colorectal cancer mCRC that is microsatellite stable or mismatch repair proficient MSSpMMR. The study focuses on participants whose cancer did not respond well to first-line chemotherapy or who have not received systemic therapy before. The trial is divided into three parts to assess safety, dosing, and effectiveness of the treatments in shrinking or controlling tumor growth. The study treatments include varying doses of BNT314 and BNT327, given by intravenous infusion, along with one of two standard chemotherapy regimens or Bevacizumab combined with chemotherapy. Part A tests safety and dose levels, Part B optimizes the dose of BNT314 with chemotherapy, and Part C compares the combination treatments to standard care in a randomized manner. Participants receive treatment until disease progression, intolerance, or study end, with an expected average treatment duration of 6 to 10 months. Participants will undergo screening, treatment, and safety follow-up periods, followed by long-term monitoring for survival and side effects. Researchers will regularly assess safety through an internal review committee and independent monitoring for Part C. Outcome measures include dose limiting toxicities, adverse events, tumor response rates, progression-free survival, and overall survival, with assessments continuing for up to 57 months after treatment begins.

Researchers are evaluating the safety, effectiveness, best dose, and how the body processes BNT326 when used alone or combined with other immunotherapy drugs in adults with advanced solid tumors. These tumors are either metastatic, recurrent without further treatment options, or have relapsed after previous therapy. The study includes patients with different types of advanced cancers such as melanoma, lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer. In Part 1, participants receive BNT326 alone across several cancer-specific groups, including cutaneous melanoma, non-small cell lung cancer with or without specific mutations, rare melanomas, advanced tumors, and cervical cancer. Part 2 evaluates BNT326 alone or combined with another immunotherapy drug called pumitamig. Participants are assigned to different dose levels, sometimes randomly, depending on their cancer type and group. The study includes a screening period, treatment for up to 24 months or until progression or other reasons, and follow-up periods. During the study, participants undergo assessments including tumor tissue sampling, monitoring of treatment side effects, blood tests to measure drug levels, and evaluations of tumor response and survival. Safety is closely followed up to 42 or 90 days after treatment ends, with longer-term monitoring for up to 38 months Part 1 or 48 months Part 2. Participants overall response rates, adverse events, and pharmacokinetics are key outcomes. The study is sponsored by BioNTech SE and includes open-label, adaptive design across two phases.

Researchers are evaluating TD001, an antibody-drug conjugate targeting prostate-specific membrane antigen PSMA, in men with metastatic PSMA-expressing castration-resistant prostate cancer CRPC. This first-in-human, open-label, multicenter Phase 12 trial aims to assess the safety, tolerability, drug levels, and preliminary antitumor activity of TD001 to support dose optimization for further study. Participants receive TD001 through intravenous infusion at escalating doses to find the recommended Phase 2 doses RP2Ds. Multiple dosing schedules may be tested during the dose escalation part, followed by an expansion phase where groups receive TD001 at the RP2Ds until disease progression or other reasons to stop treatment. During the study, participants will be closely monitored for safety and tolerability, including adverse events and laboratory tests, over treatment and follow-up periods ranging from approximately 8 to 21 months. Researchers will measure pharmacokinetics, response rates, progression-free survival, overall survival, and immunogenicity. The total estimated follow-up includes up to 21 months to capture treatment effects and long-term safety.

Researchers are evaluating the safety, tolerability, and effectiveness of BNT113 combined with pembrolizumab compared to pembrolizumab alone as a first treatment for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma HNSCC that tests positive for human papillomavirus 16 HPV16 and expresses the protein PD-L1. This Phase IIIII trial includes patients whose tumors have a combined positive score of 1 or higher for PD-L1. The study is designed to generate important safety and efficacy data for these treatments in this patient group. The trial consists of two parts Part A is a non-randomized safety run-in phase to confirm the safety and tolerability of BNT113 with pembrolizumab. Part B is a randomized phase comparing BNT113 combined with pembrolizumab versus pembrolizumab alone. Treatments are given by intravenous injection or infusion. Patients may receive treatment for up to 24 months. An optional pre-screening phase allows tumor samples to be tested centrally for HPV16 DNA and PD-L1 expression before entering the main trial. Participants will undergo regular assessments including monitoring for treatment-emergent adverse events, overall survival, and progression-free survival for up to 48 months. Researchers will also measure response rates and duration, disease control, and any dose adjustments due to side effects. Patients provide tumor tissue samples before treatment and are monitored closely throughout the study period. The trial aims to collect comprehensive data on safety, treatment effects, and patient outcomes over this extended follow-up.

Researchers are evaluating the safety and effectiveness of trontinemab in people aged 50 to 90 years who have early symptomatic Alzheimers disease, ranging from mild cognitive impairment to mild dementia. The study is a phase III trial designed to compare trontinemab with a placebo to better understand its impact on cognitive decline in Alzheimers patients. Participants will be randomly assigned to receive either intravenous IV trontinemab or an IV placebo. The study is double-blind, meaning neither the participants nor the researchers know who receives the drug or placebo. Treatment and monitoring will continue for 72 weeks, during which various cognitive and biological measures will be assessed. Throughout the study, participants will undergo regular assessments including cognitive tests like the Clinical Dementia Rating, Sum of Boxes CDR-SB, and the Mini-Mental State Examination MMSE. Brain imaging scans such as amyloid and tau PET scans, as well as MRI, will be used to observe changes in brain pathology. Researchers will also monitor safety by tracking adverse events, infusion reactions, and the presence of antibodies against trontinemab. Participants will be supported by a study partner and will be closely followed during the entire study period.