Maumee

Researchers are evaluating the safety, tolerability, and overall survival of an experimental therapy called E-EDV-D682/GC combined with gemcitabine and nab-paclitaxel in participants with metastatic pancreatic ductal adenocarcinoma (PDAC) who have progressed after first-line therapy. This randomized, blinded Phase I/IIa trial focuses on participants whose cancer expresses the epidermal growth factor receptor (EGFR) and who have failed prior 5-fluorouracil-based treatments. The study aims to assess whether adding the investigational nanocell therapy improves outcomes compared to standard chemotherapy alone. The investigational treatment includes E-EDV-D682, which packages a chemotherapy drug (PNU-159682) inside targeted nanocells designed to deliver the drug directly to cancer cells expressing EGFR. It is combined with EDV-GC, another nanocell product carrying an immune-stimulating agent (alpha-galactosylceramide). Participants are randomized to receive either E-EDV-D682/GC with gemcitabine and nab-paclitaxel or gemcitabine and nab-paclitaxel with placebo. Treatment cycles involve bi-weekly and weekly visits with intravenous infusions, tumor assessments by imaging at week 8, and continued treatment until disease progression or unacceptable side effects occur. The study includes an initial safety run-in phase followed by a randomized expansion phase. Participants will be involved for about 6 months during active treatment, including screening, two 7-week treatment cycles with treatment-free weeks for tumor evaluation, and a safety follow-up visit about 30 days after the last dose. Researchers will monitor adverse events continuously from enrollment until 30 days after treatment ends, as well as overall survival from first dose through treatment and for at least 12 months after discontinuation. Assessments include imaging scans, laboratory tests, performance status, and compliance with treatment protocols to evaluate safety and effectiveness.

Researchers are evaluating the safety and effectiveness of combining durvalumab and domvanalimab compared to durvalumab plus placebo in adults with locally advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) whose disease has not worsened after definitive platinum-based concurrent chemoradiation therapy. This Phase III, randomized, double-blind, placebo-controlled, international study involves multiple centers. Participants receive intravenous infusions of durvalumab and domvanalimab or durvalumab and placebo. The treatments are given after patients have completed concurrent platinum-based chemotherapy and radiation therapy with a total radiation dose of approximately 60 Gy. The study monitors patients over time to assess treatment effects and safety. During the study, participants undergo evaluations including tumor tissue analysis for PD-L1 status, performance status assessments, and monitoring of organ and marrow function. The main outcome measured is progression-free survival up to 8 years after randomization. Researchers also monitor for any adverse effects and disease progression throughout the study period.

The TEMPUS AQUARIUS Study is a non-interventional, longitudinal observational research focused on patients with hematological cancers such as Acute Myeloid Leukemia (AML) and Follicular Lymphoma (FL). It aims to collect detailed molecular and clinical data from these patient groups to better understand how biomarkers relate to real-world health outcomes across multiple blood-related diseases. This study gathers information over a long period of up to 5 years to assess changes and correlations in biomarker profiles. There are no treatments or interventions given as part of this study. Instead, researchers will collect serial blood samples and leftover tissue or bone marrow samples taken during patients' routine medical care and disease monitoring. The study includes different patient cohorts, such as those newly diagnosed or with relapsed disease, and samples will be collected at baseline and throughout their treatment journey as applicable. Participants will be involved in regular sample collections aligned with their standard care visits, allowing researchers to track molecular changes and link them to clinical outcomes. The study will analyze these biospecimens alongside clinical data to explore biomarker landscapes and their progression. This detailed data collection and follow-up will help researchers understand disease behavior and treatment responses over time, with participation lasting up to five years.

Researchers are evaluating the safety and potential treatment effects of NRM-823, a bispecific T-Cell Engager drug, in adults with locally advanced or metastatic solid tumors. These tumors include various types such as non-small cell lung cancer, triple negative breast cancer, head and neck squamous cell carcinoma, esophageal cancers, gastric and gastroesophageal junction adenocarcinomas, cervical, endometrial, and ovarian cancers. The study is a Phase 1 trial focused on assessing safety and tolerability. The study is divided into three parts: Part A assesses the safety and tolerability of NRM-823 alone. Part B expands on this by confirming safety and tolerability at the recommended dose found in Part A. Part C explores the combination of NRM-823 with an immune checkpoint inhibitor to evaluate the combined effect. Participants receive the drug as monotherapy or in combination during these phases. Participants will be monitored from enrollment until 30 days after their last dose for treatment-emergent adverse events and dose-limiting toxicities. Assessments include evaluations of liver, kidney, lung, heart, and blood function, along with performance status checks. The study tracks safety and side effects carefully throughout the treatment and follow-up periods to ensure participant well-being and gather data on the drug's effects.

Researchers are evaluating the safety, recommended dose, and antitumor activity of TRI-611 in adults with ALK-positive non-small cell lung cancer (NSCLC). This Phase 1/2 study aims to find the maximum tolerated dose and recommended phase 2 dose of TRI-611, an oral ALK molecular glue degrader, while assessing how well it works in different groups of patients based on their prior ALK-targeted treatments. The study is divided into two parts: dose escalation and dose expansion with distinct participant cohorts. In the first part, participants receive escalating doses of TRI-611 to determine the highest safe dose and the best dose for further research. The second part involves three groups of participants distinguished by their previous treatments with ALK tyrosine kinase inhibitors (TKIs). Participants will take TRI-611 continuously as long as their disease does not progress and the treatment is tolerated. The study includes initial frequent clinic visits about seven times in the first three months, followed by monthly visits every 28 days. Participants will keep a diary to record each dose of the medication and undergo regular assessments including safety monitoring and measurement of tumor response. Researchers will watch for treatment-related side effects within 28 days of the first dose and evaluate tumor response approximately 16 weeks after the last participant receives treatment in the second part. The study focuses on safety, effectiveness, and how deeply tumors respond to the treatment over time.

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study to see if it can reduce the risk of major adverse cardiovascular events (MACE-PLUS) in adults with established atherosclerotic cardiovascular disease (ASCVD) or those at high risk for a first ASCVD event. The study compares AZD0780 to a placebo and monitors participants from randomization until the primary analysis censoring date, followed by a final study closure visit. Participants will be randomly assigned to receive either oral AZD0780 or an oral placebo once daily. The treatment period lasts until the primary analysis censoring date, after which a study closure visit will occur. The study is event-driven and designed to assess the time to the first major cardiovascular event during treatment. During the study, participants will be closely monitored with various assessments to evaluate cardiovascular outcomes and safety over approximately 54 months. Researchers will track the time to first event of any component of MACE-PLUS and collect data to assess the effect of AZD0780 compared to placebo. The study includes regular visits and evaluations to ensure participant safety and adherence to treatment.

Researchers are evaluating a Phase 2 study called PUMA-ALI-1201 to find the optimal dose of alisertib combined with endocrine therapy for adults with hormone receptor-positive, HER2-negative metastatic or recurrent breast cancer. Participants have experienced disease progression after at least two prior endocrine therapy treatments. The study also aims to assess the safety, effectiveness, pharmacokinetics of alisertib combined with endocrine therapy, and to identify biomarker-defined subgroups that may benefit most from this combination treatment. Participants will receive alisertib tablets orally twice daily on days 1-3, 8-10, and 15-17 of each 28-day cycle. They will also receive investigator-selected endocrine therapy according to approved dosing schedules, which may include daily oral tablets of anastrozole, letrozole, exemestane, tamoxifen, or intramuscular injections of fulvestrant on specified days. The combination treatment will be administered in repeated 28-day cycles. Throughout the study, researchers will monitor responses to treatment by measuring outcomes such as objective response rate, duration of response, disease control rate, progression-free survival, and overall survival for up to 48 months. Safety will be tracked by recording treatment-emergent adverse events from first dose through 28 days after the last dose. The study includes regular assessments to evaluate treatment effects, side effects, and participant well-being over the course of the trial.

Researchers are evaluating ART0380, an oral drug that blocks ATR kinase, in people with advanced or metastatic solid tumors including ovarian, peritoneal, fallopian tube, endometrial, colorectal, pancreatic ductal adenocarcinoma, and acinar cell carcinoma. The study aims to find the safe dose of ART0380 alone and combined with chemotherapy drugs gemcitabine or irinotecan, understand side effects, and assess its effectiveness. This open-label Phase I/IIa trial includes participants whose cancers have DNA repair defects or lack ATM protein and some specific cancer types. Participants receive ART0380 by mouth in 21-day cycles either intermittently (several days on then off) or continuously daily. Gemcitabine is given on days 1 and 8, and irinotecan is given by 90-minute infusion on the same days in combination groups. The study has different parts to find dosing levels and to evaluate safety, tolerability, pharmacokinetics, and initial effectiveness of ART0380 alone or combined with the chemotherapy drugs. During the study, participants undergo regular evaluations including scans every 6 to 9 weeks to monitor tumor response, and safety assessments for side effects throughout treatment and up to 30 days after the last dose. Researchers track adverse events and measure progression-free survival and tumor response rates over up to 2 years. Participants are expected to be available and willing to follow study procedures and assessments during the trial period.

Researchers are evaluating MCLA-158, a bispecific antibody targeting EGFR and LGR5, in patients with advanced or metastatic solid tumors such as metastatic colorectal cancer (mCRC) and head and neck squamous cell carcinoma (HNSCC). This Phase 1/2, open-label, multi-center, and multi-national study includes an initial dose escalation phase that has been completed to find the recommended Phase II dose (RP2D) of MCLA-158. The study further explores the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and anti-tumor activity of MCLA-158 alone or combined with other treatments in selected solid tumor types dependent on EGFR signaling. The study involves several parts: a dose escalation phase to determine the RP2D of MCLA-158 as a single agent, followed by dose expansion cohorts where MCLA-158 is given at 1500 mg every two weeks either alone or in combination with other therapies. Combination treatments include MCLA-158 with pembrolizumab, FOLFIRI chemotherapy, or FOLFOX chemotherapy in different patient groups. Expansion cohorts focus on patients with advanced head and neck cancer or metastatic colorectal cancer, with some cohorts closed and others currently enrolling. Participants will undergo tumor biopsies, imaging scans, and laboratory tests to assess measurable disease and organ function, along with safety and treatment response monitoring over months to years. Researchers will track adverse events, dose modifications, treatment discontinuations, response rates, and exposure-safety relationships. The study includes long-term follow-up up to 36 months to evaluate overall treatment outcomes and safety in this patient population.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and effectiveness of subcutaneous Trastuzumab Deruxtecan (T-DXd) combined with hyaluronidase in adults with metastatic solid tumors. This phase 1 study focuses on participants with various metastatic solid tumors, including breast cancer, non-small cell lung cancer with HER2 mutations, gastric cancer, and other heavily pretreated solid tumors, assessing the impact of this combination treatment. The study includes a dose escalation phase where Trastuzumab Deruxtecan doses are increased to find the recommended dose for expansion (RDE). In the expansion phase, participants receive the RDE of T-DXd. The treatment is given subcutaneously along with hyaluronidase, and dosing schedules are designed to monitor safety and tolerability closely. The study aims to determine the optimal dose and assess potential toxicities and side effects. Participants will be involved in the study for up to approximately nine months, from the start of the treatment until 21 days after the last dose. During this time, researchers will monitor treatment emergent adverse events, dose limiting toxicities, and pharmacokinetics by collecting clinical data and laboratory tests. The study also involves regular assessments of disease progression, safety monitoring, and tumor evaluations using imaging to measure response to treatment.