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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
178
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).
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.
Centre Hospitalier Le Mans
Le Mans, France
RECRUITINGCHU de Lille - Hôpital Claude Huriez
Lille, France
RECRUITINGCHU de Limoges - CHU Dupuytren
Limoges, France
RECRUITINGHospices Civils De Lyon - Hôpital Lyon Sud
Lyon, France
Part 1: Incidence and severity of adverse events (AE)
Assessed as the number and grade of adverse events assessed by CTCAE v5.0
Time frame: 12 months
Part 2 and Part 3: Complete response (CR) (group 1)
Assessed per Lugano Response Criteria for Malignant Lymphoma
Time frame: 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
Time frame: 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
Time frame: 12 months
Maximum Plasma Concentration (Cmax)
Assessment of the peak plasma concentration (Cmax)
Time frame: 12 months
Maximum Plasma Concentration (Tmax)
Assessment of the time to peak plasma concentration (Tmax)
Time frame: 12 months
Area Under the Concentration Time-Curve (AUC)
Assessed of the area under the plasma concentration versus time curve (AUC)
Time frame: 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.
Time frame: 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.
Time frame: 12 months
Overall survival (OS)
Assessed as the time from first treatment to death.
Time frame: 12 months
Progression-free survival (PFS)
Assessed as time from the time from first treatment to the first occurrence of disease progression or death.
Time frame: 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.
Time frame: 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.
Time frame: 12 months
Time to response
Assessed as the time from the first treatment to the time of first response (CR or PR).
Time frame: 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.
Time frame: 12 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
CHU Montpellier - Hôpital Saint Eloi
Montpellier, France
RECRUITINGAPHP - Hôpital Pitié-Salpêtrière
Paris, France
RECRUITINGCHU de Bordeaux - Hôpital Haut-Lévêque
Pessac, France
RECRUITINGWojewódzki Szpital Specjalistyczny w Białej Podlaskiej
Biała Podlaska, Poland
RECRUITINGIN-VIVO Bydgoszcz Sp. z o.o.
Bydgoszcz, Poland
RECRUITINGKlinika Hematologii I Transplantologii Uck
Gdansk, Poland
NOT_YET_RECRUITING...and 26 more locations