Epcoritamab in Relapsed/Refractory Marginalzone Lymphoma A MULTICENTER OPEN LABEL SINGLE-ARM PHASE II STUDY of the GERMAN LYMPHOMA ALLIANCE (GLA)
Cycle 1:
Epcoritamab:
Priming Dose (Cycle 1 Day 1) 0.16 mg
First Intermediate Dose (Cycle 1 Day 8) 0.8 mg
Second Intermediate Dose (Cycle 1 Day 15) 3 mg
First Full Dose (Cycle 1 Day 22) 48 mg
Cycle 2-12:
Epcoritamab will be administered SC at 48 mg in 4-week cycles (ie, 28 days).
• Cycle 2-3: Days 1, 8, 15, and 22 (once weekly)
• Cycle 4-9: Days 1 and 15 (every 2 weeks)
• Cycles 10 to 12: Day 1 (every 4 weeks)
geplant, Rekrutierung startet in Kürze
Herr Prof. Dr. med. Christian Buske
Laubacher Weg 7
88416 Ochsenhausen
christian.buske@uni-ulm.de
Universitätsklinikum Ulm - Ulm (Institution, 12054)
Institut für Experimentelle Tumorforschung
Albert-Einstein-Allee 11
89081 Ulm
The objective of the trial is to test the efficacy and safety of the treatment of Epcoritamab SC in patients with relapsed/refractory MZL. For efficacy, the rate of complete remissions (according to the GELA criteria for gastric MALT or to the Cheson 2007 criteria for non-gastric extranodal and nodal MZL) after therapy will be primarily analysed. For toxicity, treatment associated adverse events, quality of life, and cumulative incidence of secondary malignancies will be documented.
Inclusion Criteria:
Patients must have a proven pathological diagnosis of MZL, diagnosed by a reference pathology center.
Patients must meet the following inclusion criteria to be eligible for participation in this study:
• Confirmed CD20 positive relapsed/refractory MALT Lymphoma OR
• Confirmed CD20 positive relapsed/refractory splenic MZL OR
• Confirmed CD20 positive relapsed/refractory nodal MZL
53 patients
It will follow the assumption that the CR rate 4 weeks after the end of treatment (after the scheduled 12 cycles of treatment or in the case of early termination at the time point of the early termination visit) will be better than 26%, as reported for BTK inhibitors in MZL based on the observation of about 50% CR rate in relapsed/refractory follicular lymphoma for Epcoritamab.
Sample size/Power Calculation:
For sample size calculation the one-sided one sample exact binomial test was used. According to the above data, the CRR must be better than 26%. Based on an expected CRR for Epcoritamab of at least 44% (conservatively assumed smaller than in follicular lymphoma), a significance level of 10% one-sided (reflecting the phase 2 nature of the trial) and a power of 90%, 50 fully evaluable patients will be necessary to show that the bi-specific antibody will be a promising candidate for challenging alternative chemotherapy-free approaches (SAS PROC POWER, SAS 9.4; 50 patients is the first number of patients with a stable power at least 90%). It is expected, that the rate of patients not starting Epcoritamab treatment will be at most 5%. According to these parameters, the study will enroll a maximum of 53 subjects.
Primary Endpoint:
• CR rate (CRR) determined 4 weeks after the end of treatment (after the scheduled 12 cycles of treatment or in the case of early termination at the time point of the early termination visit)
Secondary Endpoint(s):
• Overall response rate (CR, PR, CR or PR)
• Best response (BOR): CR, OR
• Time to best response: CR, OR
• Time to first response (OR/CR)
• Progression free survival (PFS)
• Time to treatment failure (TTF)
• Duration of Response (DR)
• Cause specific survival (CSS)
• Overall survival (OS)
• Quality of life
• Safety
See above
• ECOG performance status e 3
• History of a non-lymphoid malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for e1 year prior to study enrolment visit, other Stage 1 cancer treated with a curative intent and currently in complete remission, for e3 years
• Central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of transformation to a high-grade or diffuse large B-cell lymphoma
• Has had prior chemotherapy (systemic anti-cancer therapy) or targeted small molecule therapy within 2 weeks prior to study Day 1
• Has received prior therapy with a bi-specific anti-CD20xCD3 antibody
• Treatment with any other investigational agent or participating in another clinical trial with an investigational product within 4 weeks prior to entering this study or within 5 x the half-life (t1/2) of the investigational product, whichever is longer
• Has received prior radiotherapy within 2 weeks of start of study treatment.
• Evidence of circulating lymphocytes (> 10.000 cells/µl)
one year treatment, two years follow-up
ca. 15
Universitätsklinikum Ulm (Sponsor)
PI Christian Buske
15
wird noch festgelegt
Ja
