Malvern

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.

Researchers are investigating treatments for adults with metastatic breast cancer that is estrogen receptor-positive, HER2-negative, and expresses gastrin releasing peptide receptor (GRPR). This study focuses on patients who have experienced disease progression after endocrine therapy combined with CDK4/6 inhibitors. The trial aims to find the best doses and schedules of [177Lu]Lu-NeoB combined with capecitabine and to evaluate the preliminary anti-tumor activity of this combination in this patient population. Participants will receive [177Lu]Lu-NeoB, a radioligand therapy, along with capecitabine, a chemotherapy drug. The study includes a phase I dose escalation to determine recommended doses, starting with 150mCi of [177Lu]Lu-NeoB every 6 weeks and capecitabine given twice daily for 14 days followed by 7 days off. Depending on safety, different dose levels and schedules will be explored. Phase II will randomize participants to treatment regimens based on phase I results. Imaging with [68Ga]Ga-NeoB PET/CT or PET/MRI will be performed during screening and after treatment in phase II to assess tumor GRPR expression. Participants will attend study visits approximately every 3 weeks for the first 9 months, then every 6 weeks, for treatment administration, safety monitoring, and tumor assessments. Tumor scans occur every 9 weeks until month 18, then every 12 weeks until month 36, and as needed afterwards. After stopping treatment, safety follow-up lasts 8 weeks, with longer-term follow-up for up to 5 years. Researchers will monitor safety, dose tolerability, tumor response, progression-free and overall survival, and other outcomes related to treatment effectiveness and side effects.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and preliminary effectiveness of AMO959 combined with lutetium (177Lu) vipivotide tetraxetan (AAA617) and an androgen receptor pathway inhibitor (ARPI) in adult males with PSMA-positive metastatic castration resistant prostate cancer (mCRPC). The study focuses on participants who have failed one prior ARPI treatment, with or without prior taxane chemotherapy exposure. The trial is a Phase Ib/II open-label study designed to assess these treatments in this specific patient population. The study includes two phases. Phase Ib involves dose escalation of AMO959 alone and then combined with AAA617 and ARPI (either abiraterone or enzalutamide) in small groups to determine safety, tolerability, and the recommended dose for expansion. Phase II randomizes participants into three groups to receive the recommended dose(s) of AMO959 plus AAA617 and ARPI or AAA617 plus ARPI alone. Treatment administration and dose escalation meetings occur during the initial phase to monitor safety and dosing. Participants will be closely monitored for adverse events, dose-limiting toxicities, dose adjustments, and drug exposure for up to 24 to 45 months depending on the phase. Effectiveness will be assessed by measuring biochemical response through PSA levels. Eligibility involves imaging to confirm PSMA-positive disease and specific disease progression criteria. The study also tracks drug tolerability and participant safety throughout the treatment and follow-up periods.

Researchers are investigating HMBD-001, an anti-HER3 antibody, in combination with cetuximab with or without docetaxel in participants who have advanced squamous cell cancers. This Phase Ib/II open-label study aims to evaluate the safety, tolerability, and efficacy of these treatments in multiple centers. The study includes participants with various advanced squamous cell carcinomas, such as lung, head and neck, esophageal, cervical, cutaneous, and nasopharyngeal cancers. Participants receive HMBD-001 intravenously once weekly alongside cetuximab weekly, which may include a loading dose on the first day of treatment. Some participants also receive docetaxel every three weeks at a dose of 60 or 75 mg/m². The study has multiple arms where treatments are given according to the participant's cancer type and prior therapies. Tumor biopsies and other assessments are part of the study requirements. During the study, participants are closely monitored for adverse events from consent until 30 days after their last dose. Safety is assessed, including dose-limiting toxicities during the first 21-day cycle. Researchers also evaluate progression-free survival for up to six months. Participants undergo regular evaluations, including tumor measurements and health assessments, to understand treatment effects and safety. The study duration varies depending on treatment response and follow-up periods.

This research aims to evaluate the safety and effectiveness of BMS-986504, a selective PRMT5 inhibitor, when combined with Nab-paclitaxel and Gemcitabine, compared to a placebo combined with Nab-paclitaxel and Gemcitabine. The study focuses on participants with untreated metastatic Pancreatic Ductal Adenocarcinoma (PDAC) who have a specific genetic alteration called homozygous MTAP deletion. This is a randomized Phase 2/3 trial designed to explore treatment options for this patient population. Participants will be assigned to receive either BMS-986504 at specified doses on certain days along with Nab-paclitaxel and Gemcitabine, or a placebo with the same chemotherapy drugs. The treatments are given according to protocol schedules. Some participants may have received up to one cycle of Nab-paclitaxel and Gemcitabine before starting the study treatment, provided they did not experience disease progression or intolerable side effects. The initial cycle must be completed before randomization. During the study, researchers will monitor participants for progression-free survival and overall survival for up to three years after the last participant is randomized. Assessments include measuring tumor response using established criteria (RECIST v1.1). Participants will undergo evaluations to track safety, treatment effects, and disease status throughout the trial period.

This research focuses on men with prostate cancer who have previously participated in an enzalutamide clinical study sponsored by Astellas or Medivation. It aims to gather long-term safety information from participants who continue to benefit from enzalutamide treatment. This is a Phase 2 open-label extension study designed to monitor ongoing treatment effects after the initial study has completed its primary analysis or evaluation period. Participants will continue their previous treatment regimens, which may include enzalutamide taken orally once daily. Some may also receive abiraterone acetate with prednisone or leuprolide acetate depending on their prior study enrollment. Dose adjustments are allowed with medical monitor approval. The first visit of this study should occur within seven days of the last visit of the prior study unless treatment is temporarily paused. Participants are asked to return to their study site every 24 weeks for safety reviews, including adverse event monitoring and medication checks. At visits every 12 weeks, participants return unused study drugs and receive new supplies if needed. Safety data, including all adverse events and serious adverse events, are collected from consent until study completion, which may last up to 96 months. The study follows local standard care guidelines and includes a post-marketing phase in South Korea.

Researchers are conducting a Phase I, multi-center, open-label study to evaluate ATG-022 in patients with advanced or metastatic solid tumors. The study includes patients whose tumors have progressed despite standard treatments, or who are intolerant or not suitable for standard therapies. It aims to find the best tolerated dose and further assess safety, tolerability, and efficacy, especially in tumors expressing Claudin 18.2. The study has two parts: a Dose Escalation Phase and a Dose Expansion Phase. In the Dose Escalation Phase, patients receive increasing doses of ATG-022 every 21 days, starting at 0.3 mg/kg and increasing through defined dose levels using a "3+3" design. The Dose Expansion Phase will treat patients with Claudin 18.2-positive tumors at the maximum tolerated or recommended Phase II dose to gather more safety and effectiveness data. Participants will be closely monitored through tumor biopsies, imaging assessments using RECIST v1.1 criteria, and safety evaluations throughout the study. Life expectancy of at least 12 weeks and good performance status are required. The primary outcomes include determining dose-limiting toxicities, maximum tolerated dose, and recommended Phase II dose within 21 days. Contraception use and pregnancy testing are part of participant requirements to ensure safety.

Researchers are evaluating the safety, tolerability, and recommended dosing of BMS-986340, both alone and combined with nivolumab or docetaxel, in adults with advanced solid tumors. This first-in-human phase 1/2 study focuses on various advanced cancers including cervical, gastric/gastroesophageal, colorectal, lung, head and neck, renal, urothelial, pancreatic, melanoma, ovarian, and triple-negative breast cancers. Participants must have progressive disease after prior therapies and measurable tumors accessible for biopsy. Participants receive specified doses of BMS-986340 alone or combined with nivolumab (BMS-936558-01) or docetaxel on scheduled days. The study includes initial treatment phases with these drugs administered in specified protocols. Biopsies before and during treatment are collected for biomarker analysis. Treatment groups assess the safety and proper dosing of these combinations in the advanced cancer setting. During the study, participants undergo tumor biopsies, imaging scans, and regular health assessments to monitor disease progression and treatment effects. Researchers track adverse events, including serious and dose-limiting toxicities, over up to 120 weeks. Safety monitoring includes evaluating events leading to treatment discontinuation or death. The study documents tolerability and gathers data to guide future dosing and combination strategies for these advanced cancers.

Researchers are conducting a Phase 1, multi-center, open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary anti-tumor effects of D3L-001 in adults with HER2-positive advanced solid tumors. This first-in-human study aims to understand how this investigational treatment behaves and is tolerated in patients with this specific type of cancer. Participants will receive D3L-001 as a biological therapy administered intravenously. The study includes dose escalation and dose expansion phases to determine the maximum tolerated dose and observe dose-limiting toxicities. Each treatment cycle lasts 21 days, and dosing adjustments will be made based on safety and tolerability data. Throughout the study, participants will be monitored from screening until 30 days after their last dose for adverse events. Safety follow-up will assess any side effects, while pharmacokinetic and pharmacodynamic evaluations will be conducted to understand the drug's behavior and effects. The primary outcomes include the number of participants experiencing adverse events and the determination of the maximum tolerated dose at the end of the first treatment cycle.

Researchers are conducting a Phase 1/2 clinical trial to study the safety, tolerability, pharmacokinetics, pharmacodynamics, and early effectiveness of D3S-001 alone or in combination with other therapies in people with advanced solid tumors that have a KRAS p.G12C mutation. This trial is a first-in-human, multicenter, open-label study focusing on tumors that are either metastatic or locally advanced and progressing despite previous treatments. Participants will receive D3S-001 orally every day in 21-day treatment cycles. The study may include combination therapies with drugs given intravenously, such as pembrolizumab, cisplatin, carboplatin, pemetrexed, and cetuximab. The trial includes dose-escalation and dose-expansion phases to evaluate different dosing levels and treatment combinations. During the study, participants will be monitored closely for adverse events and dose-limiting toxicities from the first dose until 30 days after the last dose, with each treatment cycle lasting 21 days. Researchers will assess safety, how the drug behaves in the body, and preliminary treatment effects. Participants will also undergo evaluations of their tumor response and organ function, with follow-up to ensure safety throughout the trial period.