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

NCT06534437 | Recruiting Phase 2 DMC

• 1 other identifier: JASPIS-01
• Study Type: interventional
• Target: 178
• Locations: 4 countries
• Sites: 36

Brief Summary

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.

Conditions

Non-Hodgkin Lymphoma, B-cell

Keywords

Relapsed; Refractory; Aggressive

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (12)

• Part 2 and Part 3, Incidence and severity of AE

  12 months

• Maximum Plasma Concentration (Cmax)

  12 months

• Maximum Plasma Concentration (Tmax)

  12 months

• Area Under the Concentration Time-Curve (AUC)

  12 months

• Impact of treatment on patient reported outcomes (PRO)

  12 months

Study Arms (2)

MEN1703 + glofitamab

EXPERIMENTAL

• 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: MEN1703; Drug: Glofitamab

Gofitamab

ACTIVE COMPARATOR

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

Interventions

MEN1703 DRUG

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).

Also known as: SEL24, Dapolsertib hydrochloride

MEN1703 + glofitamab

Glofitamab DRUG

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.

Gofitamab; MEN1703 + glofitamab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old
• Documented histological confirmation of aggressive B-cell non-Hodgkin lymphoma including DLBCL NOS and transformed indolent B-cell lymphoma
• 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)
• 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.
• Availability of lymph node tissue at Screening (or archival sample) (part 2 participants only)
• Life expectancy of ≥12 weeks.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2
• Adequate organ function at Screening
• Adequate hematologic function

You may not qualify if:

• Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening.
• 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.
• Concurrent participation in another therapeutic clinical study.
• 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.
• Prior treatment with a PIM inhibitor.
• Group 1 only: Any prior therapy with a bispecific antibody targeting CD3 and CD20.
• Known risk of allergy to the study drugs, MEN1703 (group 1 and 2) or glofitamab (group 1) or their excipients
• Contraindication to all uric acid lowering agents.
• Major surgery within 1 month prior to first dose of study drug.
• Hematopoietic stem cell transplant within 4 months prior to first dose of study drug.
• Requires systemic immune-modulating therapy (regardless of dose) or has confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression.
• Exposed to live or live attenuated vaccine(s) within 4 weeks prior to signing the informed consent form (ICF).
• 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.
• Known human immunodeficiency virus (HIV) infection
• Current active liver disease from any cause

Sponsors & Collaborators

• Ryvu Therapeutics SA: lead
• Menarini Group: collaborator

Study Sites (36)

Centre Hospitalier Le Mans

Le Mans, 72037, France

RECRUITING

CHU de Lille - Hôpital Claude Huriez

Lille, France

RECRUITING

CHU de Limoges - CHU Dupuytren

Limoges, 87042, France

RECRUITING

Hospices Civils De Lyon - Hôpital Lyon Sud

Lyon, 69310, France

RECRUITING

CHU Montpellier - Hôpital Saint Eloi

Montpellier, 34490, France

RECRUITING

APHP - Hôpital Pitié-Salpêtrière

Paris, 75651, France

RECRUITING

CHU de Bordeaux - Hôpital Haut-Lévêque

Pessac, 33600, France

RECRUITING

Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej

Biała Podlaska, Poland

RECRUITING

IN-VIVO Bydgoszcz Sp. z o.o.

Bydgoszcz, Poland

RECRUITING

Klinika Hematologii I Transplantologii Uck

Gdansk, Poland

NOT YET RECRUITING

Szpitale Pomorskie Sp. z o.o.

Gdynia, Poland

RECRUITING

Narodowy Instytut Onkologii im. Marii Skłodowskiej Curie, Państwowy Instytut Badawczy

Gliwice, Poland

RECRUITING

Pratia Hematologia Sp. z o.o.

Katowice, Poland

RECRUITING

Pratia MCM Kraków

Krakow, Poland

RECRUITING

SP ZOZ Szpital Uniwersytecki w Krakowie

Krakow, Poland

NOT YET RECRUITING

Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, Poland

RECRUITING

Aidport Sp. z o.o.

Skórzewo, Poland

RECRUITING

Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu

Torun, Poland

RECRUITING

Lux Med Onkologia Sp. z o.o.

Warsaw, Poland

RECRUITING

Wojskowy Instytut Medyczny - Państwowy Instytut Badawczy

Warsaw, Poland

RECRUITING

Hospital Universitari Vall D Hebron

Barcelona, 08035, Spain

RECRUITING

Clinica Universidad De Navarra

Madrid, 28027, Spain

RECRUITING

MD Anderson Cancer Center

Madrid, 28033, Spain

RECRUITING

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, Spain

NOT YET RECRUITING

Hospital Clínico Uni versitario Virgen de la Arrixaca

Murcia, 30120, Spain

NOT YET RECRUITING

Clinica Universidad De Navarra

Pamplona, 31008, Spain

RECRUITING

Hospital Universitario De Navarra

Pamplona, 31008, Spain

RECRUITING

Hospital Universitario De Salamanca

Salamanca, 37007, Spain

RECRUITING

Hospital Universitario Virgen De La Macarena

Seville, 41009, Spain

RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, Spain

NOT YET RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

RECRUITING

The Royal Marsden Hospital

London, United Kingdom

NOT YET RECRUITING

The Christie NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Plymouth Hospitals NHS Trust

Plymouth, United Kingdom

RECRUITING

The Royal Marsden Hospital

Sutton, United Kingdom

NOT YET RECRUITING

St George's Hospital

Tooting, United Kingdom

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Recurrence; Aggression

Interventions

glofitamab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Social Behavior

Central Study Contacts

Head of Clinical Operations

CONTACT

+48 123140200; clinicaltrials@ryvu.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2024
• First Posted: August 2, 2024
• Study Start: December 5, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

PL (13); GB (6); FR (7); ES (10)