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.
Participant 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). Participant previously exposed to BTK inhibitor at first line is eligible. Participant in failure of CAR-T cell first line is eligible.
Primary refractory participants (i.e., with a progressive disease) to the BTKi and Venetoclax combination will not be eligible.
Participant 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.
Participant 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.
None
Parallel
Obinutuzumab
Drug1000 mg/40mL
Glofitamab
Drug10mg/mL
Venetoclax Oral Product
Drug10mg, 50mg and 100mg tablets
Zanubrutinib Oral Capsule
Drug80mg capsules
PFS at the end of C17 (each cycle is 21 days)
The primary efficacy endpoint is the PFS at 12 months (end of C17) from first dose of study treatment, in each cohort: Zanubrutinib/Venetoclax/Glofitamab for cohorts A and C, Venetoclax/Glofitamab for cohort B, as determined by imaging central review (Lugano 2014 criteria),
Overall Response Rate (ORR) and Complete Response Rate (CRR)
ORR and CRR as determined by PET-CT evaluation according to Lugano 2014 (imaging central review and local assessment) and at end of C35 (24 months) determined by CT-scan only
PFS at the end of C17 as determined by investigator
PFS at 12 months (end of C17) from first dose of study treatment as determined by investigator (Lugano 2014 criteria
Duration of response (DOR)
Duration of response (DOR) as determined by investigator (Lugano 2014 criteria) defined as time from first documented Complete Response or Partial Response to date of disease progression or death,
Event-free survival (EFS)
Event-free survival (EFS) as determined by investigator (Lugano 2014 criteria) defined as time from first dose of study treatment to earliest of: progression, next anti-lymphoma treatment, or death.
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The Lymphoma Academic Research Organisation
Lead sponsor
BeiGene
Collaborator
Hoffmann-La Roche
Collaborator
