Phase II Study of Glofitamab With Venetoclax +/- Zanubrutinib in High-risk Mantle-cell Lymphoma

Conditions

• Lymphoma, Mantle-Cell

Eligibility Criteria

Sex

ALL

Age

18 Years - 79 Years

Healthy Volunteers

Not accepted

Interventions

• Obinutuzumab — DRUG
  1000 mg/40mL
• Glofitamab — DRUG
  10mg/mL
• Venetoclax Oral Product — DRUG
  10mg, 50mg and 100mg tablets
• Zanubrutinib Oral Capsule — DRUG
  80mg capsules

Study Details

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.

Key Dates

Start date

Feb 21, 2025

Status verified

Feb 2026

Primary completion

May 31, 2028

Completion

Mar 31, 2032

Study Design

Enrollment

100 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort A - POD24
  * Obinutuzumab IV infusion 2000 mg flat dose at C1D1 or Splited in 2 doses of 1000 mg at C1D1 and C1D2 * Glofitamab IV infusion 2.5 mg C1D8 10 mg C1D15 30 mg C2D1 and C3D1 (infusion during min 4 hours ) 30 mg Each D1 for C4 to C6 (Infusion during min 2 hours ) 30 mg Each D1 for C7 to C12 (Infusion during min 90 min) * Zanubrutinib PO 320 mg total daily dose (QD) From C1D2 continuously until end C35 * Venetoclax PO 20 mg/d C2D3 to C2D7 50 mg/d C2D8 to C2D14 100 mg/d C2D15 to C2D21 200 mg/d C3D1 to C3D7 400 mg/d From C3D8 continuously until end C35
• Experimental: Cohort B - BTKI failure
  * Obinutuzumab IV infusion 2000 mg flat dose at C1D1 or Splited in 2 doses of 1000 mg at C1D1 and C1D2 * Glofitamab IV infusion 2.5 mg C1D8 10 mg C1D15 30 mg C2D1 and C3D1 (infusion during min 4 hours ) 30 mg Each D1 for C4 to C6 (Infusion during min 2 hours ) 30 mg Each D1 for C7 to C12 (Infusion during min 90 min) * Venetoclax PO 20 mg/d C2D3 to C2D7 50 mg/d C2D8 to C2D14 100 mg/d C2D15 to C2D21 200 mg/d C3D1 to C3D7 400 mg/d From C3D8 continuously until end C35
• Experimental: Cohort C - first Line
  * Obinutuzumab IV infusion 2000 mg flat dose at C1D1 or Splited in 2 doses of 1000 mg at C1D1 and C1D2 * Glofitamab IV infusion 2.5 mg C1D8 10 mg C1D15 30 mg C2D1 and C3D1 (infusion during min 4 hours ) 30 mg Each D1 for C4 to C6 (Infusion during min 2 hours ) 30 mg Each D1 for C7 to C12 (Infusion during min 90 min) * Zanubrutinib PO 320 mg total daily dose (QD) From C1D2 continuously until end C35 * Venetoclax PO 20 mg/d C2D3 to C2D7 50 mg/d C2D8 to C2D14 100 mg/d C2D15 to C2D21 200 mg/d C3D1 to C3D7 400 mg/d From C3D8 continuously until end C35

Primary Outcome Measure

PFS at the end of C17 (each cycle is 21 days) [ Time Frame: end of cycle 17 (each cycle is 21 days) ]

Central Contacts

• Julie JULIE ASSEMAT
  +33 (4) 27 01 27 51
  [email protected]