This open-label, multicenter, three cohorts, phase II study is designed to assess a combination of Zanubrutinib/Venetoclax/Glofitamab or Venetoclax/Glofitamab in high-risk subjects with either first line or R/R Mantle Cell Lymphoma (MCL).
Three independent cohorts will be run:
* Cohort A will include subjects with a primary refractory or progressive disease within 24 months from initiation of first line treatment (POD 24). * Cohort B will be open for subjects with R/R MCL and refractory or progressive to a BTK inhibitor given previously (\>24 months if first line). * Cohort C will only enrol newly diagnosed and untreated MCL subjects with very high-risk features.
Subject must be primary refractory or in progression within 24 months from initiation of first line treatment (POD24 defined as time between D1C1 of the first treatment line and ICF signature)) (including an anti-CD20 combined with chemotherapy). Subject previously exposed to BTK inhibitor at first line is eligible. Subject in failure of CAR-T cell first line is eligible.
Primary refractory subjects (ie with a progressive disease) to the BTKi and Venetoclax combination will not be eligible.
Subject must be R/R MCL and refractory or progressive to a BTK inhibitor given in a previous line of treatment (the number of treatment lines is not limited). If first progression, time from diagnosis (defined as D1C1 of the first treatment line) to inclusion (defined as the date of ICF signature) must be superior to 24 months.
Subject previously exposed to Bcl-2 therapy and/or relapsing post CAR-T cell therapy is eligible, except if they presented a progressive disease under BTKi and Venetoclax combination.
Proven or previously known CD20 negative status on FFPE IHC at time of MCL relapse or diagnosis.
For subjects in Cohort A and B: previously refractory to treatment by BTK inhibitor and Bcl-2 therapy combination.
Any prior therapy with a bispecific antibody targeting CD3 and CD20.
Current or past history of central nervous system or meningeal involvement by lymphoma.
The Lymphoma Academic Research Organisation
Lead sponsor
BeiGene
Collaborator
Hoffmann-La Roche
Collaborator