Evaluation of LB-208 (HTR1B Antagonist) in Adult Patients With Relapsed or Refractory Solid Tumours and Lymphoma (SERONCO-1)
Phase I, first-in Human, Open-label, Dose Escalation and Cohort Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics, and Antitumour Activity of LB-208 (HTR1B Antagonist) in Adult Patients With Relapsed or Refractory Solid Tumours and Lymphoma
This clinical study is investigating a new experimental medicine called LB-208, developed for the treatment of advanced solid tumors and lymphomas in adult patients whose disease has relapsed, not responded to treatment, or for whom no suitable standard treatment option remains. This is a Phase I trial, meaning it is an early-stage study in humans. At this stage, the main goal is not yet to prove definitive effectiveness, but rather to better understand the safety of the medicine, how it behaves in the body, and what dose may be most appropriate for future studies.
LB-208 is an oral compound that works by blocking a target called HTR1B. According to the protocol, it is considered a first-in-class treatment, meaning it belongs to a new therapeutic category and has a novel mechanism of action in this setting. The drug is given orally, once a day, under fasting conditions, in continuous 28-day cycles, with no breaks between cycles.
The study is open-label and uses a dose-escalation design. This means that both the medical team and the patients know which treatment is being given, and that the first groups of patients receive lower doses, which are gradually increased if tolerance is acceptable. The design used is the well-known 3+3 model: initially, 3 patients are treated at a given dose level. If no major safety concerns are seen, the dose is increased for the next group. If significant side effects appear, more patients may be enrolled at the same dose level or the escalation strategy may be adjusted. This approach helps identify the maximum tolerated dose and the recommended dose for future studies.
The main objective of the trial is to assess the safety and tolerability of LB-208 and determine the dose that can be recommended for further clinical development. To do this, researchers closely monitor adverse events, laboratory test results, physical examinations, vital signs, electrocardiograms, and other clinical parameters. A particularly important part of the study is the identification of dose-limiting toxicities (DLTs), which are significant side effects occurring during the first treatment cycle and help define whether a dose is tolerable.
In addition to safety, the study also examines pharmacokinetics, meaning how the medicine is absorbed, distributed, metabolized, and eliminated by the body. Blood samples are collected at different time points to measure how much LB-208 is present in the bloodstream and for how long. This information is essential to understand how the treatment works in practice and to help optimize dosing.
The study also includes pharmacodynamic and exploratory biomarker analyses. These assessments aim to better understand whether the medicine is having the expected biological effect and whether there are tumor or blood markers that may help identify patients more likely to benefit from treatment in future studies. Although this early trial is not primarily designed to prove anti-tumor efficacy, researchers will also evaluate preliminary signs of clinical activity, such as tumor shrinkage, disease stabilization, duration of response, and progression-free survival.
Patients taking part in the study must meet a series of eligibility criteria. In general, they must be adults with advanced cancer for which standard options are no longer effective or appropriate, have a good enough general condition to undergo experimental treatment, and meet the required organ function and laboratory parameters. As in all clinical trials, there are also exclusion criteria intended to protect patient safety, such as certain uncontrolled medical conditions, specific previous treatments, or other factors that could interfere with interpretation of the results.
Participation in this trial may offer some patients access to an innovative therapy that is not otherwise available. However, because it is a Phase I study, there are also important uncertainties. The benefits cannot be guaranteed, the most appropriate dose is still being defined, and unexpected side effects may occur. For this reason, patients are followed very closely by the clinical team throughout the study.
Overall, LB-208 / SERONCO-1 is an early clinical study designed to determine whether this new oral HTR1B inhibitor can be administered safely, to define the best dose for future development, and to generate the first clinical information on its potential role in treating advanced cancer. The knowledge gained from this study may help guide the next stages of development and determine whether LB-208 should move forward into later-phase trials.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Tipo de estudio
Tipo de estudio
Inscripción (Estimado)
Inscripción
Fase
Fase
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
Estudio Contacto
- Nombre: Sponsor, Clinical Project Manager
- Número de teléfono: +34 684732794
- Correo electrónico: lb208_fih_ct@leukosbiotech.com
Ubicaciones de estudio
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Barcelona
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Barcelona, Barcelona, España, 08035
- Reclutamiento
- Vall d'Hebron Barcelona Hospital Campus
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Contacto:
- Study coordinator, Phase I CTS Coordinator
- Número de teléfono: +34 684732794
- Correo electrónico: lb208_fih_ct@leukosbiotech.com
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Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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Written informed consent obtained prior to performing any protocol related procedure.
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Age ≥ 18 years at the time of signing the informed consent.
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Histologically or cytologically confirmed diagnosis of advanced solid tumours or lymphoma who have failed, are intolerant to or are considered ineligible for standard of care anti-cancer treatments.
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ECOG performance status of 0-1.
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Participants must be able to take oral medications.
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Participants must have adequate bone marrow function:
Absolute neutrophil count (ANC) ≥ 1.5x 109/L. Platelets ≥ 100x 109/L. Haemoglobin ≥ 9 g/dL.
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Participants must have adequate renal and liver function:
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x upper limit normal (ULN) (≤ 5x ULN in case liver metastases).
Total bilirubin ≤ 1.5x ULN. Creatinine clearance ≥ 50 mL/min (Cockroft-Gault formula).
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Life expectancy ≥ 3months.
Specific additional criteria for dose escalation:
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Evaluable disease by RECIST 1.1 (that applies to patients with solid tumours) or according to Lugano (2014; patients with lymphoma).
Specific additional criteria for PK/PD dedicated cohorts:
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Measurable disease by RECIST 1.1 or Lugano (2014).
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Participants must have disease amenable to undergo biopsies.
Exclusion Criteria:
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Concomitant systemic chemotherapy, hormonal therapy, and immunotherapy for the treatment of cancer.
Hormone-replacement therapy or oral contraceptives for hormone sensitive cancers.
Gonadotropin-releasing hormone agonists or antagonists for prostate cancer. Bisphosphonates. Angiogenesis inhibitors.
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Medications that are known to prolong the QT interval.
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Participants with New York Heart Association (NYHA) Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) <40%.
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Participants with heart-rate corrected QT (QTc) interval ≥450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome).
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Systemic anti-cancer therapy in the 3 prior weeks or 5 half-lives whichever is shorter.
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Participants taking sensitive CYP 2B6 and CYP 2C8 substrate medications as defined by FDA drug- drug interaction (DDI) Website are excluded from the study.
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Palliative radiotherapy for bone metastases in the 1 week prior to Cycle 1, Day 1.
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Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.
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Uncontrolled intercurrent illness that according to the investigator might limit compliance with study requirements, might confound the assessment of the study endpoints, or might affect study compliance.
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Untreated brain metastasis.
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Leptomeningeal disease.
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Spinal cord compression not treated with surgery and/or radiation.
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Pregnant or breastfeeding women.
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Female participants of childbearing potential not willing to take highly contraceptive methods during dosing and 6 months after stopping study treatment.
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Female participants not willing to refrain from donating oocytes during dosing and 6 months after stopping study treatment.
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Male participants with partners of childbearing potential not willing to use a highly effective contraceptive methods during dosing and 3 months after stopping study treatment.
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Male participants not willing to refrain from donating sperm during dosing and 3 months after stopping study treatment.
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Cancer history that according to the investigator might confound the assessment of the study endpoints.
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Participants with known HIV infection who have a CD4+ count <300/μL, a detectable viral load, or who are not receiving highly active antiretroviral therapy (HAART).
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Active hepatitis B infection (hepatitis B surface antigen [HbsAg] positive) without receiving antiviral treatment.
Participants who are HbsAg positive must receive antiviral treatment with lamivudine, tenofovir, entecavir, or other antiviral agents, starting at least ≥7 days before the initiation of study treatment, to be eligible.
Participants with antecedents of hepatitis B (e.g., anti-hepatitis B core (anti-HBc) positive, HbsAg, and hepatitis B virus [HBV]-DNA negative) are eligible.
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Positive test for hepatitis C virus (HCV) RNA. Participants in whom HCV infection resolved spontaneously (i.e., positive HCV antibodies without detectable HCV RNA), or who achieved a sustained response after antiviral treatment and show absence of detectable HCV RNA ≥6 months (with the use of interferon [IFN]-free regimens) or ≥12 months (with the use of IFN-based regimens) after cessation of antiviral treatment, are eligible.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
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Experimental: LB-208
Participants with relapsed or refractory advanced solid tumors or lymphoma receive oral LB-208 once daily in continuous 28-day cycles. The study includes a dose-escalation phase followed by PK/PD-directed expansion cohorts to optimize dose selection. |
LB-208 is considered a first-in-class treatment and is given orally, once a day, under fasting conditions, in continuous 28-day cycles, with no breaks between cycles. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Incidence of Treatment related Adverse events (Safety and Tolerability)
Periodo de tiempo: Patients are followed from treatment start to the end of participation. Discontinuation reasons (e.g., disease progression) are in the protocol. Because progression timing varies, treatment duration is individualized, so no fixed timeframe can be set.
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The main objective of the trial is to assess the safety and tolerability of LB-208. Adverse events (AEs), including determination of DLTs, serious adverse events (SAEs), and AEs leading to discontinuation. The severity of AEs will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. |
Patients are followed from treatment start to the end of participation. Discontinuation reasons (e.g., disease progression) are in the protocol. Because progression timing varies, treatment duration is individualized, so no fixed timeframe can be set.
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Maximum Tolerated Dose
Periodo de tiempo: Treatment duration is individualized and lacks a fixed timeframe because disease progression timing is unknown. Treatment duration is estimated to be up to 18 months. Maximum tolerated dose is assessed only during the escalation phase.
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This approach helps identify the maximum tolerated dose and the recommended dose for future studies. |
Treatment duration is individualized and lacks a fixed timeframe because disease progression timing is unknown. Treatment duration is estimated to be up to 18 months. Maximum tolerated dose is assessed only during the escalation phase.
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Colaboradores
Colaboradores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Inicio del estudio
Finalización primaria (Estimado)
Finalización primaria
Finalización del estudio (Estimado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- 2023-509532-25-00
- 2023 (Subvención/contrato del NIH de EE. UU.)
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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