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Researchers are evaluating the safety and effectiveness of elenestinib BLU-263 combined with symptom directed therapy SDT compared to placebo plus SDT in adults with indolent systemic mastocytosis ISM whose symptoms are not well controlled by SDT alone. This randomized, double-blind, placebo-controlled Phase 23 study includes multiple parts to assess different doses and durations of elenestinib treatment, including an open-label extension for participants finishing earlier phases. The study also enrolls participants who have previously received an approved selective KIT inhibitor and includes pharmacokinetic groups. Participants receive oral elenestinib or placebo once daily alongside SDT, which is personalized based on individual symptom management needs. Part 1 focuses on short-term treatment lasting up to 12 weeks, while Part 2 extends treatment to approximately 48 weeks. Part 3 and other parts allow treatment for up to about 5 years. The study monitors participants through these phases to evaluate how elenestinib affects symptoms, disease markers, and safety over time. During the study, participants undergo regular assessments of symptoms using the ISM-Symptom Assessment Form ISM-SAF, laboratory tests including serum tryptase and KIT D816V allele levels, bone marrow evaluations, and quality of life measures. Researchers track adverse events and changes in disease-related factors at various points up to 5 years. This thorough monitoring helps measure treatment effects and safety over both short and long-term periods, with total participation lasting several years depending on the study part.

Researchers are studying treatments for locally advanced or metastatic colorectal cancer mCRC that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This trial aims to evaluate if adding the targeted therapies calderasib and cetuximab to the standard chemotherapy regimen mFOLFOX6 can provide better outcomes compared to mFOLFOX6 with or without bevacizumab. The study focuses on the safety and tolerability of these combinations and whether they can help people live longer without their cancer growing or spreading. Participants will be assigned to one of two groups. One group will receive calderasib orally, cetuximab every two weeks, and mFOLFOX6 chemotherapy including oxaliplatin, leucovorin or levofolinate calcium, and 5-fluorouracil every two weeks. The other group will receive mFOLFOX6 chemotherapy with or without bevacizumab every two weeks, based on the investigators decision. Treatments will continue until certain stopping criteria are met. During the study, participants will be monitored for side effects and treatment tolerance, with regular assessments of cancer progression. Researchers will measure outcomes such as dose-limiting toxicities, adverse events, progression-free survival, and overall survival. Quality of life will also be evaluated through questionnaires. The study may last up to several years, with monitoring continuing for safety and effectiveness throughout the treatment period and follow-up.

Researchers are evaluating the effects of an investigational medicine called PGN-EDODM1 to understand how safe and tolerable multiple doses are for adults with myotonic dystrophy type 1 DM1. This phase 2 study compares PGN-EDODM1 to a placebo to assess its safety and tolerability in people with this condition. Participants will be randomly assigned to receive either PGN-EDODM1 or a placebo. The treatment is given by intravenous infusion once every 4 weeks for a total of 12 weeks. Those in the PGN-EDODM1 group will receive ascending doses, while the placebo group will receive saline infusions on the same schedule. During the study, participants will be monitored for safety by tracking adverse events from the start through Day 112. Researchers will measure drug levels in the blood, changes in muscle tissue, myotonia severity, hand grip strength, and mobility using specific tests. The total participation lasts through about 16 weeks, including treatment and follow-up assessments.

Researchers are evaluating the safety, effectiveness, and how the body processes and responds to NXT007 prophylaxis compared with emicizumab prophylaxis in people aged 12 years and older who have severe or moderate congenital hemophilia A without factor VIII FVIII inhibitors, or any severity of hemophilia A with FVIII inhibitors. This phase 3, randomized, open-label study aims to compare these treatments to better understand their impact on bleeding rates and treatment burden. Participants will be randomly assigned to one of two main treatment groups. One group will receive NXT007 prophylaxis administered subcutaneously using an integrated drug-device combination product. The other group will receive emicizumab prophylaxis via subcutaneous injections, starting with weekly loading doses for 4 weeks, then maintenance dosing at various intervals depending on prior treatment status. After the main treatment period, participants from both arms can continue or switch to NXT007 in an open-label extension phase. Throughout the study, participants will be closely monitored with regular assessments, including measuring annualized bleed rates for different types of bleeds, treatment burden questionnaires, and safety evaluations such as adverse event monitoring and laboratory tests. These evaluations will continue throughout approximately 3.5 years of study participation to provide comprehensive data on treatment effects and safety.

Researchers are evaluating the effectiveness, safety, and how the body processes and responds to NXT007 prophylaxis compared to Factor VIII FVIII prophylaxis in people aged 12 years and older with severe or moderate congenital hemophilia A who do not have inhibitors. This phase III study focuses on participants who have previously been treated with FVIII prophylaxis. The goal is to understand how NXT007 performs against the current standard treatment for this condition. Participants will be randomly assigned to receive either NXT007 prophylaxis, given as a subcutaneous injection with an integrated drug-device combination product, or standard Factor VIII prophylaxis according to local dosing and frequency guidelines. After the main six-month treatment period, those receiving NXT007 may continue this treatment in an open-label extension, and those initially on FVIII prophylaxis may switch to NXT007 during this extension phase. During the study, participants will be closely monitored through various assessments, including tracking the annualized bleed rate ABR for treated bleeds over six months, questionnaires evaluating treatment burden and impact on social and recreational activities, and safety evaluations such as adverse events, injection-site reactions, and antibody development against NXT007. The study will continue follow-up for approximately 3.5 years to gather comprehensive data on treatment effects and safety.

Researchers are evaluating the safety, efficacy, and optimal dosing of a combination of two investigational treatments, BNT323 trastuzumab pamirtecan and BNT327 pumitamig, in people with advanced breast cancer. This includes those with hormone receptor-positive or -negative, HER2-positive, HER2-low, HER2-ultralow, HER2-null breast cancer, or triple-negative breast cancer. The study is a Phase III multi-site, open-label trial with a focus on advanced breast cancer treatment options. The study has two parts. Part 1 involves dose escalation of BNT323 combined with BNT327 to determine the recommended Phase 2 dose using six different dose levels. Part 2, which begins after Part 1 completion, includes dose optimization and exploratory cohorts. Cohort 1 in Part 2 uses randomization into four treatment arms, including combination therapy at different doses and monotherapies of either BNT323 or BNT327. Other cohorts receive the recommended dose without randomization. Participants will undergo assessments including tumor scans and cardiac function tests, with monitoring for side effects and tumor response up to 36 months. Researchers will track dose-limiting toxicities and treatment-emergent adverse events during early treatment cycles and monitor objective response rates and disease control over time. Safety and efficacy data will be collected through scheduled visits and tumor assessments during and after treatment to evaluate the study drugs effects and tolerability.

Researchers are evaluating the safety, effectiveness, optimal dose, and behavior of an investigational drug called BNT326, alone or combined with other immunotherapy agents, in adults with advanced solid tumors. This study includes patients with tumors that have either spread metastatic, returned after treatment, or progressed despite previous therapies, across various cancer types such as melanoma, lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer. Participants are divided into two parts Part 1 tests BNT326 alone in different tumor-specific groups, some with dose randomization to find optimal dosing. Part 2 evaluates BNT326 alone or combined with another investigational drug called pumitamig in several cancer types, with some groups receiving randomized doses and others non-randomized treatments. Treatments are given via intravenous infusion, with some oral medications combined in Part 1. The study includes dose escalation and randomization phases, and treatment can continue for up to 24 months or until disease progression or other reasons. During the study, participants undergo screening, treatment, safety follow-up, efficacy follow-up, and long-term survival monitoring phases. Researchers assess adverse events, treatment responses, disease progression, and drug behavior in the body using clinical evaluations and laboratory tests. Follow-up assessments occur up to approximately 38 months for Part 1 and 48 months for Part 2, with continued treatment possible for those benefiting from the therapy. The study aims to gather comprehensive data on safety, dosing, and effectiveness in this patient population.

Researchers are evaluating the safety, tolerability, and therapeutic effects of BNT113 combined with pembrolizumab compared to pembrolizumab alone as a first-line treatment for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma HNSCC positive for human papilloma virus 16 HPV16 and expressing the protein PD-L1 with a combined positive score of 1 or higher. This is an open-label, multi-site, Phase IIIII clinical trial consisting of two parts an initial safety run-in phase and a randomized phase. In the safety run-in phase Part A, patients receive BNT113 in combination with pembrolizumab to confirm safety and tolerability at selected dose levels. The randomized phase Part B compares BNT113 combined with pembrolizumab against pembrolizumab monotherapy. Treatments are given by intravenous injection or infusion and continue for up to 24 months. An optional pre-screening phase allows tumor samples to be tested for HPV16 DNA and PD-L1 expression before the main trial screening. Participants will be closely monitored throughout the study. Assessments include safety evaluations, tumor response, and survival outcomes such as overall survival and progression-free survival. Tumor tissue samples must be provided for testing. Researchers will measure treatment-emergent adverse events, response rates, duration of response, and disease control. The study may last up to 48 months, with ongoing safety and efficacy monitoring during and after treatment.

This research is a global, multicenter, prospective observational registry studying patients with Pompe disease, including both late-onset LOPD and infantile-onset IOPD forms. It enrolls both untreated patients and those receiving approved therapies to better understand the long-term safety, real-world effectiveness, and quality of life impacts of treatments for Pompe disease. The study also aims to describe the natural history of untreated Pompe disease. Participants include groups receiving different enzyme replacement therapies such as Cipaglucosidase alfa with Miglustat, other approved ERTs like Alglucosidase alfa or Avalglucosidase alfa, as well as untreated individuals who are not on any medical therapy for Pompe disease. No experimental treatments are given as this is an observational study tracking real-world treatment use and outcomes. During the study, participant data on adverse events, treatment effectiveness, quality of life, and patient-reported outcomes will be collected over a period of at least five years. Researchers will monitor safety through the frequency of adverse events and serious adverse events. Participants health and treatment impacts will be regularly evaluated to provide long-term insights into Pompe disease management and outcomes.

Researchers are evaluating the efficacy and safety 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 progressed after definitive platinum-based concurrent chemoradiotherapy cCRT. This Phase III, randomized, double-blind, placebo-controlled, international study aims to provide new insights into treatment options for this patient population. Participants will receive either durvalumab and domvanalimab or durvalumab plus placebo as intravenous infusions every four weeks, beginning on Day 1 and continuing for up to 12 months. The study includes two groups one receiving the combination of durvalumab and domvanalimab, and the other receiving durvalumab with a placebo. Both treatments are given through infusion to assess their effects on disease progression and safety. During the trial, participants will undergo regular assessments including monitoring progression-free survival for up to 8 years after randomization. Other measures include overall survival, response rates, duration of response, and various time-to-event outcomes related to disease progression and symptom deterioration. Researchers will also evaluate drug concentrations and immune responses approximately 12 weeks after the last dose. Participants can expect scheduled visits for infusions and evaluations as part of this long-term study.