P1103: INMIND: A PHASE 3 STUDY OF TAFASITAMAB PLUS LENALIDOMIDE AND RITUXIMAB VERSUS PLACEBO PLUS LENALIDOMIDE AND RITUXIMAB FOR RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (FL) OR MARGINAL ZONE LYMPHOMA (MZL)

Abstract

Background: Patients (pts) with indolent non-Hodgkin lymphoma (NHL) subtypes FL or MZL respond to first-line treatment but relapse is common; there is no standard treatment for pts with relapsed/refractory (R/R) FL or MZL. Tafasitamab (TAFA) is an Fc-engineered humanized monoclonal antibody (mAb) against CD19, which is broadly expressed in FL and MZL and regulates proliferation via B-cell receptor signaling. In preclinical studies, TAFA has shown activity against NHL cell lines in combination with rituximab (anti-CD20 mAb) and lenalidomide (LEN). TAFA monotherapy demonstrated 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), TAFA + LEN followed by TAFA alone demonstrated an ORR of 57.5% (n/N=46/80) with CR of 40% (n/N=32/80) and median DOR of 34.6 mo (95% CI: 26.1–NR), in pts with R/R diffuse large B-cell lymphoma (FDA approved indication). These observations suggest a potential clinical benefit of TAFA + LEN and rituximab for pts with R/R FL or MZL. Aims: Phase 3 double-blind, placebo-controlled, randomized study designed to investigate whether TAFA + LEN and rituximab provides improved clinical benefit compared with LEN and rituximab in pts with R/R FL or MZL. Methods: Pts will be randomized 1:1 to receive TAFA (12 mg/kg IV on days 1, 8, 15, and 22 of 28-day cycle [cycles 1–3], then days 1 and 15 [cycles 4–12]) + LEN (20 mg PO QD [or starting dose 10 mg PO QD if creatinine clearance ≥30 to <60 mL/min], 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) + LEN and rituximab. Stratification will include progression of disease within 24 mo (FL; yes vs no), refractoriness to prior anti-CD20 mAb therapy (FL; yes vs no), and number of prior lines of therapy (FL or MZL; <2 vs ≥2). Radiological (PET) assessment will be performed at baseline, every 12 (± 2) weeks in year 1, 16 (± 2) weeks in years 2–3, and 24 (± 3) weeks in years 4–6; additional assessment performed within 4 (± 2) weeks if progressive disease confirmed before end-of-treatment (EOT) visit. The primary study endpoint is PFS (investigator assessed [INV] by Lugano 2014 criteria) for pts with FL. Key secondary endpoints are PFS (INV) in the overall population (FL and MZL), PET-CR rate (INV) at EOT (90 days after last treatment) and OS in pts with FL. Other secondary endpoints include PET-CR rate (INV) at EOT and OS in the overall population, and ORR (INV), DOR (INV), health related quality of life, safety, and minimum residual disease-negativity rate at EOT in FL and the overall population. 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 + 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 across North America, Europe, and Asia Pacific. Results: Not applicable. Summary/Conclusion: Not applicable.