Lahiry, Anirban

7540 Background: Tafasitamab is a humanized, Fc-modified anti-CD19 monoclonal antibody that enhances antibody-dependent cellular cytotoxicity and phagocytosis. It is FDA-approved with LEN for adult patients (pts) with relapsed/refractory (R/R) DLBCL ineligible for autologous stem cell transplantation. First-MIND (NCT04134936) is a Phase Ib, open-label, randomized study of tafa + R-CHOP or tafa + LEN + R-CHOP in newly diagnosed DLBCL. Methods: Eligible pts were ≥18 years, treatment-naïve, with histologically confirmed DLBCL not otherwise specified, international prognostic index (IPI) 2–5 and ECOG performance status (PS) 0–2. Pts with known double- or triple-hit and transformed lymphoma were excluded. Treatment (Tx) comprised six 21-day cycles of tafa (12 mg/kg IV, Day [D] 1, 8, 15) + R-CHOP (arm A) or tafa (12 mg/kg IV, D1, 8, 15) + LEN (25 mg orally, D1–10) + R-CHOP (arm B). G-CSF and VTE prophylaxis was mandatory. Primary objective is safety; secondary objectives are ORR, PET-CR rate at end of Tx, PFS, long-term safety, pharmacokinetics, immunogenicity. Results: From Dec 2019 to Aug 2020, 83 pts were screened in Europe and the US; 66 were randomized (33 per arm). Data cut-off for this analysis: 9 Dec 2020; study is ongoing. Median age was 64.5 years (range 20–86). Overall, 30% (20/66) of pts were ≥70 years and many had high-risk disease: IPI 2 29%, IPI 3 46%, IPI 4 26%. ECOG PS: 47% of pts were ECOG PS 0, 44% PS 1, 9% PS 2. Most pts had stage III/IV disease (92%); 46% had bulky disease. All pts experienced a treatment-emergent adverse event (TEAE). Grade ≥3 neutropenia and thrombocytopenia occurred in 54.5% and 12.1% (arm A) and 66.7% and 30.3% (arm B) of pts, respectively (Table). Serious TEAEs occurred in 42.4% (arm A) and 51.5% (arm B) of pts. There were three deaths, unrelated to tafa and/or LEN (sepsis, urosepsis, and COVID-19 pneumonia). R-CHOP dose intensity was maintained in both arms. Among 60 pts who completed tumor assessments after cycle 3, ORR was 89.7% (arm A) and 93.5% (arm B). Conclusions: These data suggest R-CHOP + tafa or tafa + LEN is tolerable in pts with Tx-naïve DLBCL and that R-CHOP dosing is not affected. Toxicities are similar to those expected with R-CHOP or R-CHOP + LEN. Updated safety and early efficacy data will be presented at the conference. Clinical trial information: NCT04134936. [Table: see text]

Introduction Approximately 15-20% of treatment-naïve patients with diffuse large B-cell lymphoma (DLBCL) have CD20-low tumors, while CD19 is homogeneously expressed in >90% of cases of DLBCL. CD20-low DLBCL is associated with poor response to rituximab-based regimens (Johnson NA, et al. 2009). CD19 functions as a positive regulator of B-cell receptor signaling and is important for B-cell activation and proliferation and is therefore an attractive therapeutic target in addition to CD20. Tafasitamab (MOR208) is a humanized, Fc-enhanced, anti-CD19 monoclonal antibody with improved antibody-dependent cellular cytotoxicity and phagocytosis. Monotherapy with tafasitamab has shown clinical activity in relapsed/refractory (R/R) non-Hodgkin's lymphoma (Jurczak W, et al. 2018). In the Phase II, single-arm L-MIND study (NCT02399085) in patients with R/R DLBCL, combined treatment of tafasitamab with lenalidomide resulted in a high proportion of patients having a complete response (Salles GA, et al. 2020). First-MIND (NCT04134936) is a Phase Ib, randomized study of tafasitamab + R-CHOP (Arm A) or tafasitamab + lenalidomide + R-CHOP (Arm B) in patients with newly diagnosed DLBCL. Here, we report data from the safety run-in phase. Study design and methods Patients must be aged ≥18 years, treatment naïve, with histologically confirmed DLBCL not otherwise specified and have intermediate- to high-risk disease (International Prognostic Index [IPI] 2-5) and an ECOG performance status of 0-2. Known double- or triple-hit lymphoma and transformed lymphoma are excluded. Treatment consists of six 21-day cycles of tafasitamab (12 mg/kg intravenously [IV], on Day [D] 1, 8 and 15) in addition to R-CHOP (Arm A) or tafasitamab (12 mg/kg IV, on D1, 8 and 15) + lenalidomide (25 mg orally, on D1-10) in addition to R-CHOP (Arm B). Granulocyte-colony stimulating factor prophylaxis was mandatory in all patients. The study includes a safety run-in phase and a main phase. In the safety run-in phase, 24 patients were enrolled. The primary objective is to assess safety; secondary objectives include ORR, PET-CR rate at end of treatment, PFS, event-free survival, long-term safety, pharmacokinetics and immunogenicity of tafasitamab. Exploratory objectives include the assessment of circulating cell-free tumor DNA. Approximately 60 patients will be recruited in 9 countries across Europe and the US. Results Recruitment is ongoing. Thirty-six patients were randomized; 18 in each arm. The data presented for the safety run-in phase consist of 24 patients: 13 patients in Arm A and 11 patients in Arm B. All completed the first treatment cycle; 88% of patients entered into Cycle 2 and 50% of patients entered into Cycle 3 of treatment. At baseline, their median age was 67 years (range: 47-76; Arm A) and 65 years (range: 40-74; Arm B). Overall, 33% of patients were male and 67% female; IPI scores were: IPI 2, 33%; IPI 3, 42%; IPI 4, 25%. Most patients had advanced stages III/IV (92%) and approximately 50% had bulky disease. Cell of origin was determined to be germinal center B-cell (GCB) DLBCL in 13%, non-GCB DLBCL in 42% and not yet classified in 46% of cases. A total of 248 treatment-emergent adverse events (AEs) by system organ class were documented: 111 in Arm A and 137 in Arm B. Grade ≥3 neutropenia was observed in 54% (Arm A) and 46% (Arm B) of patients. Thrombocytopenia Grade ≥3 was observed in 8% (Arm A) and 18% (Arm B) of patients. Diarrhea, fatigue and vomiting were comparable between the two arms. Febrile neutropenia was uncommon in both arms, with one event each (Figure 1). To date, 23 serious AEs were observed: 11 in Arm A (Grade 2, 1; Grade 3, 6; Grade 4, 4) and 12 in Arm B (Grade 2, 3; Grade 3, 7; Grade 4, 2). One suspected unexpected serious adverse reaction was reported in Arm B - pneumocystis jirovecii pneumonia. No treatment-associated deaths occurred. Conclusions R-CHOP can be safely combined with tafasitamab or tafasitamab + lenalidomide in patients with treatment-naïve DLBCL. Toxicities appear to be similar to what is expected with R-CHOP alone or in combination with lenalidomide. Enrollment is ongoing and updated safety and early efficacy data will be presented at the meeting. Disclosures Belada: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Celgene: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Nowakowski:NanoString: Research Funding; Seattle Genetics: Consultancy; Curis: Consultancy; MorphoSys: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Kite: Consultancy; Kymera: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees. André:Takeda: Consultancy; Karyopharm: Consultancy; Gilead: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Research Funding; Seattle Genetics: Consultancy; Abbvie: Consultancy; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Amgen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Johnson & Johnson: Research Funding; Celgene: Other, Research Funding; CHU UCL Namur, site Godinne, Yvoir, Belgium: Current Employment; Bristol-Myers-Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Stevens:Amgen, MorphoSys: Consultancy. Trněný:Takeda: Consultancy, Honoraria, Other: Travel Expenses; Bristol-Myers Squibb Company: Consultancy, Honoraria, Other: Travel Expenses; Amgen: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel Expenses; Roche: Consultancy, Honoraria, Other: Travel Expenses; MorphoSys: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Celgene: Consultancy; Janssen: Consultancy, Honoraria, Other: Travel Expenses; Gilead: Consultancy, Honoraria, Other: Travel Expenses. Pérez Persona:Celgene: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Jannsen: Consultancy, Speakers Bureau; Amgen: Consultancy; Abbvie: Consultancy, Speakers Bureau; Takeda: Consultancy. Klöpfer:MorphoSys AG: Current Employment. Brackertz:MorphoSys AG: Current Employment. Lohrmann:MorphoSys AG: Current Employment. Lahiry:MorphoSys AG: Current Employment. Shah:MorphoSys AG: Current Employment. Fingerle-Rowson:MorphoSys AG: Current Employment. Brugger:MorphoSys AG: Current Employment. Burke:Epizyme: Consultancy; Roche: Consultancy; Bristol Myers Squibb: Consultancy; Kura: Consultancy; Celgene: Consultancy; Adaptive Biotechnologies: Consultancy; Gilead: Consultancy; Seattle Genetics: Speakers Bureau; AbbVie: Consultancy; Verastem: Consultancy; Bayer: Consultancy; Astra Zeneca: Consultancy; Adaptive: Consultancy; Morphosys: Consultancy.