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.
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.
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.
Parallel
MEN1703
DrugMEN1703 (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).
Glofitamab
DrugGlofitamab 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.
Part 1: Incidence and severity of adverse events (AE)
Assessed as the number and grade of adverse events assessed by CTCAE v5.0
Part 2 and Part 3: Complete response (CR) (group 1)
Assessed per Lugano Response Criteria for Malignant Lymphoma
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
Part 2 and Part 3, Incidence and severity of AE
Assessed as the number and grade of adverse events assessed by CTCAE v5.0
Maximum Plasma Concentration (Cmax)
Assessment of the peak plasma concentration (Cmax)
Maximum Plasma Concentration (Tmax)
Assessment of the time to peak plasma concentration (Tmax)
Area Under the Concentration Time-Curve (AUC)
Assessed of the area under the plasma concentration versus time curve (AUC)
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Ryvu Therapeutics SA
Lead sponsor
Menarini Group
Collaborator
