JASPIS-01

CLINICAL STUDY

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.
TREATMENT
Dapolsertib and glofitamab (mono and combo) in DLBCL
STUDY OVERVIEW
Over the last few years, there have been recent advances in the treatment paradigm in R/R DLBCL, with the advent of CAR-T cell therapies and bispecific antibodies. These therapeutic modalities have improved outcomes in relapsed/refractory (R/R) DLBCL, but many patients still relapse, highlighting an unmet medical need.

The PIM kinase family (PIM1, PIM2, PIM3) plays a pro-survival role in cancer by influencing key cellular processes. High PIM expression and mutations are linked to poor prognosis, especially in the ABC subtype of DLBCL. PIMs interact with key oncogenes like MYC and BCL6, and their simultaneous inhibition reduces MYC levels and induces cytotoxicity in DLBCL cells.

A licensing agreement with Menarini was signed in March 2017, and Menarini holds global development and commercial rights to dapolsertib. Initially, dapolsertib was developed as a potential treatment for patients with relapsed/refractory acute myeloid leukemia (r/r AML).

More details on the completed Phase I/II clinical study in AML can be found at ClinicalTrials.gov under NCT06534437
MILESTONE
Phase II data in 2026

Explore your eligibility for the JASPIS-01 clinical trial

Study population

Women and man 18 Years and older.

Study design

The study consists of 3 parts, to investigate MEN173 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 at a dose selected from part 2 in combination with glofitamab or glofitamab alone.

Inclusion Criteria

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.

Exclusion Criteria

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
Ongoing drug-induced pneumonitis.
Ongoing inflammatory bowel disease.
Active known second malignancy
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.
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.
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.
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.
Any disease, syndrome or condition which may significantly affect drug intake via oral route.
Planning to become pregnant or breastfeed during treatment and for 1 month after the last dose of study drug.
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.

Participation criteria are verified by the investigator. Participation in the study is contingent upon meeting all inclusion criteria and meeting none of the exclusion criteria. The criteria provided may not be a complete list.

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