A Phase II Study Evaluating Glofitamab in Combination With Venetoclax Plus Zanubrutinib or Venetoclax Alone in Subjects With Untreated or Relapsed/Refractory High-risk Mantle-cell Lymphoma
NCT Number: NCT06558604
Acronym: GLOASIS
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Lymphoma, Mantle-Cell
Interventions: DRUG: Obinutuzumab|DRUG: Glofitamab|DRUG: Venetoclax Oral Product|DRUG: Zanubrutinib Oral Capsule
Sponsor: The Lymphoma Academic Research Organisation
Collaborators: BeiGene|Hoffmann-La Roche
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 100
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2031-12
Locations: Az Sint-Jan Brugge - Oostende Av, Brugge, Belgium|Institut Jules Bordet, Brussel, Belgium|Chu de Liege, Liège, Belgium|Chu Ucl Namur - Site Godinne, Yvoir, Belgium|Aphp - Hopital Henri Mondor, Créteil, France|Chu Dijon Bourgogne, Dijon, France|Chu de Lille - Hopital Claude Huriez, Lille, France|Institut Paoli Calmettes, Marseille, France|Chu de Montpellier, Montpellier, France|Chu de Nantes, Nantes, France|Chu Lyon-Sud, Pierre-Bénite, France|Chu de Reims - Hopital Robert Debre, Reims, France|Chu Pontchaillou, Rennes, France|Centre Henri Becquerel, Rouen, France|Institut Curie - Site Saint-Cloud, Saint-Cloud, France|Institut Curie, Saint-Cloud, France|Institut de Cancerologie Strasbourg Europe, Strasbourg, France

Summary:
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.

Primary Outcome Measures: 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),, end of cycle 17 (each cycle is 21 days)
Secondary Outcome Measures: 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, End of C3 (each cycle is 21 days), end of C6 (each cycle is 21 days), end of C12 (each cycle is 21 days), end of C17 (each cycle is 21 days), end of C26 (each cycle is 21 days))|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, end of cycle 17 (each cycle is 21 days)|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,, 72 months|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., 74 months|Disease Free Survival (DFS), Disease Free Survival (DFS) as determined by investigator (Lugano 2014 criteria) defined as time from first dose of study treatment to earliest of: progression, or death from lymphoma., 74 months|Overall Survival (OS), Overall survival defined as time from first dose of study treatment to death from any cause,, 74 months or death|Time to next anti-lymphoma treatment (TTNT), Time to next anti-lymphoma treatment (TTNT) defined as time from first dose of study treatment to earliest date of next anti-lymphoma treatment (except corticosteroids), date of next anti-lymphoma treatment (74 months)|Safety and tolerability:, Incidence of grade ≥3 adverse events, adverse events of special interest (AESI)., from ICF signature until 28 days after the last treatment administration|Minimal Residual Disease (MRD), MRD response, before Cycle 1 Day1 (baseline), end of C3 (each cycle is 21 days), end of C6 (each cycle is 21 days), end of C17 (each cycle is 21 days)