INMIND: A PHASE 3 STUDY OF TAFASITAMAB + LENALIDOMIDE AND RITUXIMAB VS PLACEBO + LENALIDOMIDE AND RITUXIMAB FOR RELAPSED/REFRACTORY FOLLICULAR OR MARGINAL ZONE LYMPHOMA

Abstract

Background: Most patients (pts) with the indolent non‐Hodgkin lymphoma (NHL) subtypes follicular lymphoma (FL) or marginal zone lymphoma (MZL) respond to first‐line treatment but relapse is common, and there is no single standard treatment for pts with relapsed/refractory (R/R) FL or MZL. Tafasitamab is an Fcengineered humanized monoclonal antibody (mAb) against CD19 which is broadly expressed in FL and MZL, and regulates B‐cell proliferation via B‐cell receptor signaling. In preclinical studies, tafasitamab has shown activity against NHL cell lines in combination with rituximab (anti‐CD20 mAb) and lenalidomide (LEN). Tafasitamab monotherapy has shown promising clinical activity in a phase 2a study in pts with R/R NHL (NCT01685008), with an ORR of 29% (n/N = 10/34) in pts with FL and 33% (n/N = 3/9) in pts with MZL. In an ongoing phase 2, single‐arm study (L‐MIND, NCT02399085), tafasitamab plus LEN followed by tafasitamab alone demonstrated an ORR of 57.5% (n/N = 46/80), CR of 40% (n/N = 32/80) and median DOR of 34.6 months (95% CI: 26.1‐NR), in pts with R/R diffuse large B‐cell lymphoma (FDA approved indication). These preclinical and clinical observations from phase 2 trials suggest a potential clinical benefit of tafasitamab plus LEN and rituximab for pts with R/R FL or MZL. Methods: This phase 3 double‐blind, placebo‐controlled, randomized study is designed to investigate whether tafasitamab plus LEN and rituximab provides improved clinical benefit compared with LEN and rituximab in pts with R/R FL or R/R MZL. Pts 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 [10 mg PO QD if creatinine clearance ≥30 to <60 mL/ minute], 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. The primary study endpoint is PFS (investigator assessed [INV] by Lugano 2014 criteria) for pts with FL. Key secondary endpoints are PFS (INV) in overall population (FL and MZL), PET‐CR rate (INV) at end of treatment (4‐8 weeks after last treatment) and OS in pts with FL. Inclusion criteria include age ≥18 y, 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, adequate systemic organ function, and high tumor burden (per GELF criteria). Exclusion criteria include prior rituximab plus LEN treatment, history of radiotherapy for other diseases (≥25% of bone marrow), nonhematologic malignancy, congestive heart failure (LVEF < 50%), active systemic infection, known CNS lymphoma, or severe immunocompromised state. inMIND (NCT04680052, EudraCT2020‐004407‐13) is currently enrolling pts; planned enrollment is 528 pts with R/R FL and 60‐90 pts with R/R MZL.