MEN1703 (SEL24) to Treat Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma (JASPIS-01) (JASPIS-01)

An Open Label, Phase 2 Clinical Trial of MEN1703 as Monotherapy and in Combination With Glofitamab in Patients With Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma

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.

Study Overview

• Status: Recruiting
• Conditions: Non-Hodgkin Lymphoma, B-cell
• Intervention / Treatment: Drug: Glofitamab; Drug: MEN1703

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 178
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Head of Clinical Operations; Phone Number: +48 123140200; Email: clinicaltrials@ryvu.com

Study Locations

• France
  • Le Mans, France, 72037
    • Recruiting
    • Centre Hospitalier Le Mans
    • Principal Investigator: Kamel Laribi, MD PhD
  • Lille, France
    • Recruiting
    • CHU de LILLE - Hopital Claude Huriez
    • Principal Investigator: Franck Morschhauser, Prof.
  • Limoges, France, 87042
    • Recruiting
    • CHU de Limoges - CHU Dupuytren
    • Principal Investigator: Julie Abraham, MD PhD
  • Lyon, France, 69310
    • Recruiting
    • Hospices Civils de Lyon - Hôpital Lyon Sud
    • Principal Investigator: Herve Ghesquieres, Prof.
  • Montpellier, France, 34490
    • Recruiting
    • CHU Montpellier - Hôpital Saint Eloi
    • Principal Investigator: Guillaume Cartron, MD PhD
  • Paris, France, 75651
    • Recruiting
    • APHP - hôpital Pitié-Salpêtrière
    • Principal Investigator: Sylvain Choquet, MD PhD
  • Pessac, France, 33600
    • Recruiting
    • CHU de Bordeaux - Hôpital Haut-Lévêque
    • Principal Investigator: Francois Xavier Gros, MD PhD
• Poland
  • Biała Podlaska, Poland
    • Recruiting
    • Wojewódzki Szpital Specjalistyczny W Białej Podlaskiej
    • Contact: Piotr Centkowski, MD PhD
    • Principal Investigator: Piotr Centkowski, MD PhD
  • Bydgoszcz, Poland
    • Recruiting
    • IN-VIVO Bydgoszcz Sp. z o.o.
    • Principal Investigator: Jarosław Czyż, Prof.
  • Gdansk, Poland
    • Not yet recruiting
    • Klinika Hematologii I Transplantologii Uck
    • Principal Investigator: Jan Zaucha, Prof.
  • Gdynia, Poland
    • Recruiting
    • Szpitale Pomorskie Sp. z o.o.
    • Principal Investigator: Adam Witkowski, MD PhD
  • Gliwice, Poland
    • Recruiting
    • Narodowy Instytut Onkologii im. Marii Skłodowskiej Curie, Państwowy Instytut Badawczy
    • Contact: Małgorzata Krawczyk-Kuliś, Prof.
    • Principal Investigator: Małgorzata Krawczyk-Kuliś, Prof.
  • Katowice, Poland
    • Recruiting
    • Pratia Hematologia Sp. z o.o.
    • Contact: Sebastian Grosicki, Prof.
    • Principal Investigator: Sebastian Grosicki, Prof.
  • Krakow, Poland
    • Recruiting
    • Pratia McM Krakow
    • Contact: Wojciech Jurczak, Prof.
    • Principal Investigator: Wojciech Jurczak, Prof.
  • Krakow, Poland
    • Not yet recruiting
    • SP ZOZ Szpital Uniwersytecki w Krakowie
    • Principal Investigator: Agnieszka Giza, MD PhD
  • Olsztyn, Poland
    • Recruiting
    • Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie
    • Contact: Janusz Hałka, MD PhD
    • Principal Investigator: Janusz Hałka, MD PhD
  • Skórzewo, Poland
    • Recruiting
    • AIDPORT Sp. z o.o.
    • Principal Investigator: Michał Kwiatek, Dr
  • Torun, Poland
    • Recruiting
    • Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu
    • Contact: Dominik Chraniuk, MD
    • Principal Investigator: Dominik Chraniuk, MD
  • Warsaw, Poland
    • Recruiting
    • LUX MED Onkologia Sp. z o.o.
    • Contact: Joanna Barankiewicz, MD PhD
    • Principal Investigator: Joanna Barankiewicz, MD PhD
  • Warsaw, Poland
    • Recruiting
    • Wojskowy Instytut Medyczny - Panstwowy Instytut Badawczy
    • Contact: Krzysztof Gawroński, MD PhD
    • Principal Investigator: Krzysztof Gawroński, MD PhD
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d Hebron
    • Principal Investigator: Crisitna Garcia Herce, MD PhD
  • Madrid, Spain, 28027
    • Recruiting
    • Clinica Universidad de Navarra
    • Principal Investigator: Miguel Angel Canales Albendea, MD PhD
  • Madrid, Spain, 28033
    • Recruiting
    • Md Anderson Cancer Center
    • Principal Investigator: Adolfo De La Fuente Burguera, MD PhD
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Universitario Puerta de Hierro Majadahonda
    • Principal Investigator: Mariano Provencio Pulla, MD PhD
  • Murcia, Spain, 30120
    • Not yet recruiting
    • Hospital Clínico Uni versitario Virgen de la Arrixaca
    • Principal Investigator: Ignacio Espanol Morales, Dr
  • Pamplona, Spain, 31008
    • Recruiting
    • Hospital Universitario de Navarra
    • Principal Investigator: Jose Maria Arguinano Perez, MD PhD
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Universidad de Navarra
    • Principal Investigator: Miguel Angel Canales Albendea, MD PhD
  • Salamanca, Spain, 37007
    • Recruiting
    • Hospital Universitario de Salamanca
    • Principal Investigator: Norma Carmen Gutierrez, Prof.
  • Seville, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen De La Macarena
    • Principal Investigator: Luis de la Cruz Merino, MD PhD
  • Zaragoza, Spain
    • Not yet recruiting
    • Hospital Universitario Miguel Servet
    • Principal Investigator: Araceli Rubio Martinez, MD PhD
• United Kingdom
  • Glasgow, United Kingdom
    • Recruiting
    • Beatson West of Scotland Cancer Centre
    • Principal Investigator: Mark Rafferty, Dr
  • London, United Kingdom
    • Not yet recruiting
    • The Royal Marsden Hospital
    • Principal Investigator: David Cunningham, Dr
  • Manchester, United Kingdom
    • Recruiting
    • The Christie NHS Foundation Trust
    • Principal Investigator: Kim Linton, Dr
  • Plymouth, United Kingdom
    • Recruiting
    • Plymouth Hospitals NHS Trust
    • Principal Investigator: David Burns, Dr
  • Sutton, United Kingdom
    • Not yet recruiting
    • The Royal Marsden Hospital
    • Principal Investigator: David Cunningham, Dr
  • Tooting, United Kingdom
    • Recruiting
    • St George's Hospital
    • Principal Investigator: Ruth Pettengell, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: 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.; Drug: 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).; Other Names: SEL24; Dapolsertib hydrochloride
Active Comparator: 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).	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Incidence and severity of adverse events (AE)	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)	Assessed per Lugano Response Criteria for Malignant Lymphoma	12 months
Part 2 and Part 3: Overall response rate (group 2)	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax)	Assessment of the peak plasma concentration (Cmax)	12 months
Maximum Plasma Concentration (Tmax)	Assessment of the time to peak plasma concentration (Tmax)	12 months
Area Under the Concentration Time-Curve (AUC)	Assessed of the area under the plasma concentration versus time curve (AUC)	12 months
Part 2 and Part 3, Incidence and severity of AE	Assessed as the number and grade of adverse events assessed by CTCAE v5.0	12 months
Impact of treatment on patient reported outcomes (PRO)	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)	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)	Assessed as the time from first treatment to death.	12 months
Progression-free survival (PFS)	Assessed as time from the time from first treatment to the first occurrence of disease progression or death.	12 months
Duration of Response (DoR)	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)	Assessed as the time from first complete response (CR) to the first occurrence of disease progression or death.	12 months
Time to response	Assessed as the time from the first treatment to the time of first response (CR or PR).	12 months
Time to next treatment	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

Collaborators and Investigators

• Sponsor: Ryvu Therapeutics SA
• Collaborators: Menarini Group

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 30, 2024
• First Submitted That Met QC Criteria: July 30, 2024
• First Posted (Actual): August 2, 2024

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Relapsed; Refractory; Aggressive
• Additional Relevant MeSH Terms: Aberrant Motor Behavior in Dementia; Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Behavioral Symptoms; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Pathological Conditions, Signs and Symptoms; Behavior; Hemic and Lymphatic Diseases; Social Behavior; Recurrence; Lymphoma, Non-Hodgkin; Aggression; glofitamab
• Other Study ID Numbers: JASPIS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No