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MEN1703 (SEL24) voor de behandeling van recidiverend of refractair agressief B-cel non-Hodgkinlymfoom (JASPIS-01) (JASPIS-01)

15 september 2026 bijgewerkt door: Ryvu Therapeutics SA

Een open label, fase 2 klinische studie met MEN1703 als monotherapie en in combinatie met glofitamab bij patiënten met recidiverend of refractair agressief B-cel non-hodgkinlymfoom

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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

178

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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).
Geneesmiddel: 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).

Andere namen:
  • SEL24
  • DapolSertib hydrochloride
Geneesmiddel: 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.
Actieve vergelijker: 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).
Geneesmiddel: 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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Part 1: Incidence and severity of adverse events (AE)
Tijdsspanne: 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)
Tijdsspanne: 12 months

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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Part 2 and Part 3, Incidence and severity of AE
Tijdsspanne: 12 months

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

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

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

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

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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Ryvu Therapeutics SA

Medewerkers

Menarini Group

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

5 december 2024

Primaire voltooiing (Geschat)

1 december 2026

Studie voltooiing (Geschat)

1 december 2026

Studieregistratiedata

Eerst ingediend

30 juli 2024

Eerst ingediend dat voldeed aan de QC-criteria

30 juli 2024

Eerst geplaatst (Werkelijk)

2 augustus 2024

Updates van studierecords

Laatste update geplaatst (Werkelijk)

18 september 2026

Laatste update ingediend die voldeed aan QC-criteria

15 september 2026

Laatst geverifieerd

1 september 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • JASPIS-01

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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