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MEN1703 (SEL24) pour traiter le lymphome non hodgkinien agressif à cellules B récidivant ou réfractaire (JASPIS-01) (JASPIS-01)

15 septembre 2026 mis à jour par: Ryvu Therapeutics SA

Un essai clinique ouvert de phase 2 sur MEN1703 en monothérapie et en association avec le glofitamab chez des patients atteints de lymphome non hodgkinien agressif à cellules B récidivant ou réfractaire

The goal of the study is to assess the safety and anti-lymphoma activity of MEN1703 (Dapolsertib hydrochloride) when given as a single-agent or combined with glofitamab to patients with relapsed/refractory (R/R) aggressive B-cell non-Hodgkin lymphoma. The study will be open to groups at the same time:

  • Group 1 - patients who have not had anti-CD3xCD20 bispecific antibody therapy but who have had at least 2 prior lines of systemic treatment for aggressive B-cell non-Hodgkin lymphoma
  • Group 2 - patients who have exhausted all standard treatment options including at least 2 prior lines of systemic treatment for aggressive B-cell non-Hodgkin lymphoma Group 1 patients will be treated for a maximum of 12 cycles. One cycle is 21 days. Group 2 with be treated until the disease progresses, therefore treatment duration is dependent on the number of treatment cycles a participant receives prior to progression.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

The study consists of 3 parts, to investigate MEN1703 (Dapolsertib hydrochloride) in combination with glofitamab in patients who are naïve to treatment with an anti-CD3xCD20 bispecific antibody (group 1) or MEN1703 alone in patients who have exhausted all standard treatment options (group 2).

Part 1 (safety run-in) and Part 2 (enrichment): patients who are naïve to treatment with an anti-CD3xCD20 bispecific antibody (group 1) will receive either 150 mg or 125 mg of MEN1703 along with glofitamab. Patients who have exhausted all standard treatment options (group 2) will receive 125 mg of MEN1703 as a single-agent.

Part 3 (optional randomized comparison): Patients who are naïve to treatment with an anti-CD3xCD20 bispecific antibody therapy will be randomized to receive either MEN1703 (Dapolsertib hydrochloride) at a dose selected from part 2 in combination with glofitamab or glofitamab alone.

Type d'étude

Interventionnel

Inscription (Estimé)

178

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • Espagne
      • Barcelona, Espagne, 08035
        • Recrutement
        • Hospital Universitari Vall D Hebron
        • Chercheur principal:
          • Crisitna Garcia Herce, MD PhD
      • Madrid, Espagne, 28033
        • Recrutement
        • MD Anderson Cancer Center
        • Chercheur principal:
          • Adolfo De La Fuente Burguera, MD PhD
      • Madrid, Espagne
        • Recrutement
        • Hospital Universitario Puerta de Hierro Majadahonda
        • Chercheur principal:
          • Mariano Provencio Pulla, MD PhD
      • Madrid, Espagne, 28027
        • Recrutement
        • Clinica Universidad De Navarra
        • Chercheur principal:
          • Miguel Angel Canales Albendea, MD PhD
      • Murcia, Espagne, 30120
        • Pas encore de recrutement
        • Hospital Clínico Uni versitario Virgen de la Arrixaca
        • Chercheur principal:
          • Ignacio Espanol Morales, Dr
      • Pamplona, Espagne, 31008
        • Recrutement
        • Clinica Universidad De Navarra
        • Chercheur principal:
          • Miguel Angel Canales Albendea, MD PhD
      • Pamplona, Espagne, 31008
        • Recrutement
        • Hospital Universitario De Navarra
        • Chercheur principal:
          • Jose Maria Arguinano Perez, MD PhD
      • Salamanca, Espagne, 37007
        • Recrutement
        • Hospital Universitario De Salamanca
        • Chercheur principal:
          • Norma Carmen Gutierrez, Prof.
      • Seville, Espagne, 41009
        • Recrutement
        • Hospital Universitario Virgen De La Macarena
        • Chercheur principal:
          • Natalia Palazon, MD PhD
      • Zaragoza, Espagne
        • Recrutement
        • Hospital Universitario Miguel Servet
        • Chercheur principal:
          • Araceli Rubio Martinez, MD PhD
  • France
      • Le Mans, France, 72037
        • Recrutement
        • Centre Hospitalier Le Mans
        • Chercheur principal:
          • Kamel Laribi, MD PhD
      • Lille, France
        • Recrutement
        • CHU de Lille - Hôpital Claude Huriez
        • Chercheur principal:
          • Franck Morschhauser, Prof.
      • Limoges, France, 87042
        • Recrutement
        • CHU de Limoges - CHU Dupuytren
        • Chercheur principal:
          • Julie Abraham, MD PhD
      • Lyon, France, 69310
        • Recrutement
        • Hospices Civils De Lyon - Hôpital Lyon Sud
        • Chercheur principal:
          • Herve Ghesquieres, Prof.
      • Montpellier, France, 34490
        • Recrutement
        • CHU Montpellier - Hôpital Saint Eloi
        • Chercheur principal:
          • Guillaume Cartron, MD PhD
      • Paris, France, 75651
        • Recrutement
        • APHP - Hôpital Pitié-Salpêtrière
        • Chercheur principal:
          • Sylvain Choquet, MD PhD
      • Pessac, France, 33600
        • Recrutement
        • CHU de Bordeaux - Hôpital Haut-Lévêque
        • Chercheur principal:
          • Francois Xavier Gros, MD PhD
  • Pologne
      • Biała Podlaska, Pologne
        • Résilié
        • Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej
      • Bydgoszcz, Pologne
        • Recrutement
        • IN-VIVO Bydgoszcz Sp. z o.o.
        • Chercheur principal:
          • Jarosław Czyż, Prof.
      • Gdansk, Pologne
        • Pas encore de recrutement
        • Klinika Hematologii I Transplantologii Uck
        • Chercheur principal:
          • Jan Zaucha, Prof.
      • Gdynia, Pologne
        • Recrutement
        • Szpitale Pomorskie Sp. z o.o.
        • Chercheur principal:
          • Adam Witkowski, MD PhD
      • Gliwice, Pologne
        • Recrutement
        • Narodowy Instytut Onkologii im. Marii Skłodowskiej Curie, Państwowy Instytut Badawczy
        • Contact:
          • Małgorzata Krawczyk-Kuliś, Prof.
        • Chercheur principal:
          • Małgorzata Krawczyk-Kuliś, Prof.
      • Katowice, Pologne
        • Résilié
        • Pratia Hematologia Sp. z o.o.
      • Krakow, Pologne
        • Recrutement
        • SP ZOZ Szpital Uniwersytecki w Krakowie
        • Chercheur principal:
          • Agnieszka Giza, MD PhD
      • Krakow, Pologne
        • Recrutement
        • Pratia MCM Kraków
        • Contact:
          • Wojciech Jurczak, Prof.
        • Chercheur principal:
          • Wojciech Jurczak, Prof.
      • Olsztyn, Pologne
        • Recrutement
        • Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie
        • Contact:
          • Janusz Hałka, MD PhD
        • Chercheur principal:
          • Janusz Hałka, MD PhD
      • Skórzewo, Pologne
        • Recrutement
        • Aidport Sp. z o.o.
        • Chercheur principal:
          • Michał Kwiatek, Dr
      • Torun, Pologne
        • Recrutement
        • Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu
        • Contact:
          • Dominik Chraniuk, MD
        • Chercheur principal:
          • Dominik Chraniuk, MD
      • Warsaw, Pologne
        • Résilié
        • Lux Med Onkologia Sp. z o.o.
      • Warsaw, Pologne
        • Résilié
        • Wojskowy Instytut Medyczny - Państwowy Instytut Badawczy
  • Royaume-Uni
      • Glasgow, Royaume-Uni
        • Recrutement
        • Beatson West of Scotland Cancer Centre
        • Chercheur principal:
          • Mark Rafferty, Dr
      • Manchester, Royaume-Uni
        • Recrutement
        • The Christie NHS Foundation Trust
        • Chercheur principal:
          • Kim Linton, Dr
      • Plymouth, Royaume-Uni
        • Recrutement
        • Plymouth Hospitals NHS Trust
        • Chercheur principal:
          • David Burns, Dr
      • Sutton, Royaume-Uni
        • Recrutement
        • The Royal Marsden Hospital
        • Chercheur principal:
          • David Cunningham, Dr
      • Tooting, Royaume-Uni
        • Recrutement
        • St George's Hospital
        • Chercheur principal:
          • Ruth Pettengell, Dr

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  1. Age ≥18 years old
  2. Documented histological confirmation of aggressive B-cell non-Hodgkin lymphoma including DLBCL NOS and transformed indolent B-cell lymphoma
  3. Relapsed or refractory disease having received at least 2 prior lines of systemic treatment and, naïve to anti-CD3xCD20 bispecific antibody treatment (group 1) or exhausted all standard, available treatment options (group 2)
  4. At least 1 measurable site of disease based on computed tomography (CT) or positron emission tomography (PET)-CT scan with involvement of 2 or more clearly demarcated lesions and or nodes.
  5. Availability of lymph node tissue at Screening (or archival sample) (part 2 participants only)
  6. Life expectancy of ≥12 weeks.
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2
  8. Adequate organ function at Screening
  9. Adequate hematologic function

Exclusion Criteria:

  1. Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening.

  2. Received anti-cancer treatments, including cytotoxic chemotherapy, radiotherapy, hormonal therapy, biologic, immunotherapy, or investigational drugs within 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug. Prior treatment with CAR-T cell or an anti-CD3xCD20 bispecific antibody therapy (permitted for Group 2 only), requires a wash out period of ≥4 weeks.

  3. Concurrent participation in another therapeutic clinical study.

  4. Ongoing clinically significant toxicity (for example, alopecia is not clinically significant) from any prior anti-cancer therapy that has not resolved to Grade 1 or less prior to the first dose of study drug.

  5. Prior treatment with a PIM inhibitor.

  6. Group 1 only: Any prior therapy with a bispecific antibody targeting CD3 and CD20.

  7. Known risk of allergy to the study drugs, MEN1703 (group 1 and 2) or glofitamab (group 1) or their excipients

  8. Contraindication to all uric acid lowering agents.

  9. Major surgery within 1 month prior to first dose of study drug.

  10. Hematopoietic stem cell transplant within 4 months prior to first dose of study drug.

  11. Requires systemic immune-modulating therapy (regardless of dose) or has confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression.

  12. Exposed to live or live attenuated vaccine(s) within 4 weeks prior to signing the informed consent form (ICF).

  13. Evidence of ongoing and uncontrolled systemic bacterial, fungal, or viral infection, except for documented Grade Common Terminology Criteria for Adverse Events (CTCAE) ≤2 infections with evidence of improvement or without evidence of worsening infection.

  14. Known human immunodeficiency virus (HIV) infection

  15. Current active liver disease from any cause

  16. Ongoing drug-induced pneumonitis.

  17. Ongoing inflammatory bowel disease.

  18. Active known second malignancy

  19. Received an agent known to be a sensitive CYP2D6 substrate or a CYP2D6 substrate with a narrow therapeutic range, a strong or moderate CYP2D6 inhibitor, or a BCRP inhibitor within 14 days or 5 half-lives (whichever is shorter), prior to the first dose of study drug.

  20. Cardiac dysfunction is defined as myocardial infarction within 6 months of study entry, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled dysrhythmias, or poorly controlled angina.

  21. Receiving treatment for active, ongoing thromboembolic event. Note: Does not apply to prophylactic treatment to prevent or avoid reoccurrence of a prior resolved event. To review with Medical Monitor where further risk assessment is needed.

  22. History of serious ventricular arrhythmia (e.g., VT or VF, ≥3 beats in a row), or QT interval corrected for heart rate (QTc) ≥480 ms.

    Note: QTc values up to 500 ms will be acceptable where patient's medical history e.g., bundle branch block, is known to cause mild QTc prolongation and the condition is well controlled.

  23. Any disease, syndrome or condition which may significantly affect drug intake via oral route.

  24. Planning to become pregnant or breastfeed during treatment and for 1 month after the last dose of study drug.

  25. Any other prior or current medical condition, intercurrent illness, surgical history, physical or 12-lead electrocardiogram (ECG) findings, laboratory abnormalities, or extenuating circumstance (e.g., alcohol or drug addiction) that, in the investigator's opinion, could jeopardize patient safety or interfere with the objectives of the study.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: MEN1703 + glofitamab

• Participants who are naïve to treatment with an anti-CD3xCD20 bispecific antibody (group 1) will be given MEN1703 orally at a dose of 150 mg daily for 7 days or 125 mg daily for 14 days, in 21-day cycles for a maximum of 12 cycles, in combination with glofitamab administered as an IV infusion in a step-up dosing schedule starting with 2.5 mg on day 8 of cycle 1, and10 mg on day 15 of cycle 1, and 30 mg on day 1 from cycle 2 onward until disease progression or withdrawal, for a maximum of 12 cycles (parts 1, 2, 3)).

All participants will be administered 1,000 mg of obinutuzumab as an IV infusion on cycle 1 day 1.

• Participants who have exhausted all standard treatment options (group 2) will receive MEN1703 as a single-agent, at a dose of 125 mg orally every-day for 14 consecutive days in consecutive 21-day treatment cycles, until progressive disease (parts 1 and 2).
Médicament: MEN1703

MEN1703 (Dapolsertib hydrochloride) is a potent dual inhibitor of proviral integration site for Moloney murine leukemia virus (PIM) kinases and Fms-like tyrosine kinase 3 (FLT3).

Autres noms:
  • SEL24
  • Chlorhydrate de dapolsertib
Médicament: Glofitamab

Glofitamab is a bispecific monoclonal antibody that binds bivalently to CD20 expressed on the surface of B-cells and monovalently to CD3 in the T-cell receptor complex expressed on the surface of T-cells.
Comparateur actif: Gofitamab

Participants who are naïve to treatment with an anti-CD3xCD20 bispecific antibody (group 1) will receive glofitamab as a single-agent administered as an IV infusion in a step-up dosing schedule starting with 2.5 mg on day 8 of cycle 1, and10 mg on day 15 of cycle 1, and 30 mg on day 1 from cycle 2 onward until disease progression or withdrawal, for a maximum of 12 cycles (part 3).
Médicament: Glofitamab

Glofitamab is a bispecific monoclonal antibody that binds bivalently to CD20 expressed on the surface of B-cells and monovalently to CD3 in the T-cell receptor complex expressed on the surface of T-cells.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Part 1: Incidence and severity of adverse events (AE)
Délai: 12 months

Assessed as the number and grade of adverse events assessed by CTCAE v5.0
12 months
Part 2 and Part 3: Complete response (CR) (group 1)
Délai: 12 months

Assessed per Lugano Response Criteria for Malignant Lymphoma
12 months
Part 2 and Part 3: Overall response rate (group 2)
Délai: 12 months

Assessed as the number of patients who achieve a complete response (CR) or partial response (PR), per Lugano Response Criteria, divided by the total number of evaluable patients
12 months

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Part 2 and Part 3, Incidence and severity of AE
Délai: 12 months

Assessed as the number and grade of adverse events assessed by CTCAE v5.0
12 months
Maximum Plasma Concentration (Cmax)
Délai: 12 months

Assessment of the peak plasma concentration (Cmax)
12 months
Maximum Plasma Concentration (Tmax)
Délai: 12 months

Assessment of the time to peak plasma concentration (Tmax)
12 months
Area Under the Concentration Time-Curve (AUC)
Délai: 12 months

Assessed of the area under the plasma concentration versus time curve (AUC)
12 months
Impact of treatment on patient reported outcomes (PRO)
Délai: 12 months

Assessed as changes in lymphoma symptoms, well-being, and general health status measured according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) consisting of 30 questions that assess five domains of patient functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), global health status/quality of life (GHS/QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All are scored from 0 to 100, with higher scores on the five domains and GHS/QoL being reflective of better health related (HR) QoL, and higher scores on the symptom scales and single items reflective of poor HRQoL.
12 months
Impact of treatment on quality of life (QOL)
Délai: 12 months

Assessed as changes in lymphoma symptoms and health related quality of life (HRQoL) as measured using the 15-item Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) including physical, social/family, emotional, and functional well-being and includes a lymphoma-specific subscale. The scale range is 0 to 60, with a higher score reflecting a better HRQoL.
12 months
Overall survival (OS)
Délai: 12 months

Assessed as the time from first treatment to death.
12 months
Progression-free survival (PFS)
Délai: 12 months

Assessed as time from the time from first treatment to the first occurrence of disease progression or death.
12 months
Duration of Response (DoR)
Délai: 12 months

Assessed as the time from first response (CR or PR) to the first occurrence of disease progression or death.
12 months
Duration of Complete Response (DoCR)
Délai: 12 months

Assessed as the time from first complete response (CR) to the first occurrence of disease progression or death.
12 months
Time to response
Délai: 12 months

Assessed as the time from the first treatment to the time of first response (CR or PR).
12 months
Time to next treatment
Délai: 12 months

Assessed as the time from the first treatment to the start date of the first therapy received after the participant has ended study treatment and received subsequent anti-lymphoma therapy.
12 months

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Ryvu Therapeutics SA

Collaborateurs

Menarini Group

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

5 décembre 2024

Achèvement primaire (Estimé)

1 décembre 2026

Achèvement de l'étude (Estimé)

1 décembre 2026

Dates d'inscription aux études

Première soumission

30 juillet 2024

Première soumission répondant aux critères de contrôle qualité

30 juillet 2024

Première publication (Réel)

2 août 2024

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

18 septembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

15 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • JASPIS-01

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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