IBCL-123 inMIND: A Phase 3 Study of Tafasitamab Plus Lenalidomide and Rituximab Versus Placebo Plus Lenalidomide and Rituximab for Relapsed/Refractory (R/R) Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL).

CONTEXT: Treatment options for patients with R/R FL or MZL are limited. Tafasitamab is an Fc-engineered humanized monoclonal antibody against CD19, which is broadly expressed in FL and MZL and regulates B-cell proliferation. Tafasitamab monotherapy showed clinical activity in a phase 2a study (NCT01685008), with an ORR of 29% (n/N=10/34) and 33% (n/N=3/9) in patients with FL and MZL, respectively. In an ongoing phase 2 study (L-MIND, NCT02399085), tafasitamab plus lenalidomide (LEN) followed by tafasitamab alone demonstrated an ORR of 57.5% (n/N=46/80) in patients with R/R diffuse large B-cell lymphoma (FDA approved indication). These observations suggest potential clinical benefit of tafasitamab plus LEN for patients with R/R FL or MZL.

OBJECTIVE: To investigate efficacy and safety of tafasitamab plus LEN as add-on to rituximab compared with LEN alone added to rituximab in patients with R/R FL or MZL.

DESIGN: Multicenter, global, randomized, double-blind, placebo-controlled, phase 3 study.

PATIENTS: ≥18 years with histologically confirmed FL (grade 1, 2, or 3a) or MZL (nodal, splenic, or extranodal), documented R/R disease, ≥1 prior systemic anti-CD20 therapy (including anti-CD20 refractory disease), ECOG PS ≤2, high tumor burden (per GELF criteria). Exclusions include prior rituximab plus LEN combination treatment, history of non-hematologic malignancy, congestive heart failure, or known CNS lymphoma. inMIND (NCT04680052, EudraCT2020-004407-13) is currently enrolling, with planned enrollment of 528 R/R FL and 60-90 R/R MZL patients.

INTERVENTIONS: Patients will be randomized 1:1 to receive tafasitamab (12 mg/kg IV on days 1, 8, 15, and 22 of a 28-day cycle [cycles 1-3], then days 1 and 15 [cycles 4-12]) plus LEN (20 mg PO QD, days 1-21/cycle for 12 cycles) and rituximab (375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1, then day 1 of cycles 2-5) OR placebo (0.9% saline solution IV) plus LEN and rituximab.

MAIN OUTCOME MEASURES: Primary endpoint is PFS (investigator-assessed [INV] by Lugano 2014 criteria) for patients with FL. Secondary endpoints include PFS (INV) in the overall population, PET-CR rate (INV) at 90 days after last treatment, and OS in patients with FL.