Abstract: 7514 Background: The Fc-enhanced CD19 antibody MOR208 and the immunomodulatory drug LEN have demonstrated single agent activity in patients (pts) with R-R DLBCL. MOR208 and LEN have shown synergy in vitro and in vivo in preclinical lymphoma models. This ongoing phase II study assesses the safety and efficacy of MOR208 + LEN in pts with R-R DLBCL. Methods: Pts 〉 18 years old with R-R DLBCL, ECOG 0–2, adequate organ function, having previously received ≥1 but not more than 3 prior therapies, including ≥1 CD20-targeting regimen and who are not candidates for autologous stem cell transplant (ASCT), are eligible. Treatment comprises up to 12, 28-day (d) cycles (C) of MOR208 12 mg/kg IV, weekly during C1–3 (loading dose d4 of C1); every second week C4–12 + LEN 25 mg po d1–21, C1–12. Pts progression-free after 12 cycles receive up to 12 additional cycles of MOR208 (every second week). The primary endpoint is the overall response rate (ORR) by central radiology assessment. Secondary endpoints include disease control, duration of response, progression-free and overall survival, safety, and response by cell of origin and other biomarkers. A preplanned safety evaluation was undertaken. Results: 31 of 80 planned pts were enrolled prior to data cutoff (3 January 2017). Median age was 74 years (range 47–82); 45% of pts received ≥2 prior lines of therapy; 23% had rituximab refractory disease; 74% had Ann Arbor stage ≥III disease; 65% had elevated lactate dehydrogenase level, and 52% had a poor revised International Prognostic Index (3-5). The most common treatment-emergent adverse events (any grade/grade ≥3 [% pts]) were neutropenia (39/26), anemia (23/0) thrombocytopenia (16/6), infections (26/10) diarrhea (13/0), pyrexia (13/0), and rashes (13/6). Of 26 response evaluable pts (median follow-up 3.3 months), ORR (investigator assessed) was 58% (15 pts), with 7 (27%) complete responses. Median time to response was 1.8 months. Conclusions: The combination of MOR208 + LEN is well tolerated and shows promising activity in pts with R-R DLBCL. Accrual and follow-up of pts is ongoing, as are cell of origin and other biomarker analyses. Clinical trial information: NCT02399085.

Abstract: 7521 Background: MOR208, an Fc-enhanced, humanized, anti-CD19 monoclonal antibody has shown single agent activity in patients (pts) with R-R DLBCL and encouraging activity when combined with LEN in the phase II L-MIND study. Here we report an update with primary endpoint and subgroup analyses (cut off June 5, 2018). Methods: Key inclusion criteria were adequate organ function, ≤3 prior lines of therapy, including ≥1 anti-CD20 therapy, and ineligibility for stem cell transplantation. Treatment comprised up to 12, 28-day (d) cycles (C) of MOR208, 12 mg/kg IV, q1w C1–3 (loading dose on d4 of C1), and q2w C4–12 + LEN 25 mg PO d1–21, C1–12. Pts progression-free after 12 C received MOR208 q2w until progression. The primary endpoint was independent review committee (IRC)-assessed ORR as per Cheson 2007 criteria. Results: Recruitment is complete (N = 81): median age 72 years (range 41–87), median of 2 prior therapies, 19 (23%) of pts had early relapse (≤12 months [mo] from diagnosis), 32 (40%) were rituximab (RTX) refractory (no response to or progression during or within 6 mo of a prior RTX therapy), 34 (42%) were refractory to their last therapy, 21/40 (26%/49%) pts had non-germinal center B cell-like (GCB)- / GCB-DLBCL, and 42 (52%) had an International Prognostic Index (IPI) of 3–5. MOR208 + LEN therapy was well tolerated; 72% of pts stayed on a LEN dose of ≥20 mg/day. Treatment-related serious adverse events, mainly infections (10%) or neutropenic fever (5%), occurred in 17% of pts. Investigator (INV)-assessed complete response (CR) and partial response rates were 33% and 25%, respectively, giving an ORR of 58%, comparable to the IRC assessment (ORR 54%; CR 32%). ORR was 46% in pts with ≥2 prior therapies, 59%/56% in rituximab- / last treatment-refractory pts, 58% in early relapse pts, 57% in pts with a baseline IPI of 3–5, and 71% in pts with non-GCB- vs 53% with GCB-DLBCL. INV-assessed median PFS and OS (ITT analysis) were 16.2 mo (95% CI: 6.3–NR) and not reached (95% CI: 18.6–NR), respectively. Conclusions: MOR208 + LEN shows encouraging activity including a durable PFS in R-R DLBCL, and in pt subgroups with poor prognosis. Clinical trial information: NCT02399085.

Abstract: Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months’ follow-up. Patients were aged 〉 18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months’ follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085.

Abstract: Introduction: The CD19 antigen is broadly and homogeneously expressed across different B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL). MOR208 is an Fc-enhanced, humanized, monoclonal antibody that targets CD19, leading to natural killer (NK) cell-mediated antibody-dependent cytotoxicity, macrophage-mediated antibody-dependent phagocytosis and direct cytotoxicity. The immunomodulatory drug, lenalidomide (LEN), has both antiproliferative and antiangiogenic effects, and can stimulate the activity of immune effectors, such as NK cells. MOR208 and LEN have each shown single agent activity in patients with relapsed or refractory (R-R) DLBCL. In addition, MOR208 and LEN have shown synergy in in vitro and in vivo lymphoma models. We present results of an ongoing, multicenter phase II study designed to assess the safety and efficacy of MOR208 combined with LEN in patients with R-R DLBCL (NCT02399085). Methods:Patients 〉 18 years of age diagnosed with DLBCL, an Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function, who had relapsed after or were refractory to at least one but not more than three prior systemic therapies, including at least one CD20-targeting regimen, and who were not candidates for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT), were eligible. Patients with primary refractory disease (defined as no response to or progression during or within 6 months after completion of frontline therapy for DLBCL) were excluded. Treatment comprises up to twelve 28-day cycles of MOR208, administered intravenously at a dose of 12 mg/kg weekly during cycles 1-3 (plus a loading dose on day 4 of cycle 1), and every second week during cycles 4-12. LEN was administered orally at a daily dose of 25 mg on days 1-21 of each cycle, for up to 12 cycles. Patients who were progression-free after 12 cycles received MOR208 every second week until progression. The primary endpoint is the objective response rate (ORR), centrally assessed, as per the International Working Group criteria 2007, incorporating PET-based imaging. Secondary endpoints include ORR as per investigator assessment, duration of response (DoR), progression-free survival (PFS) and overall survival (OS), safety, and analysis of outcomes by cell of origin and other biomarkers. Results: As of November 2017, 81 patients had been enrolled and recruitment is complete. We report here updated preliminary results with a data cutoff of 5 June 2018. Median age was 72 years (range 41-87); 40 (49%) patients had received ≥2 prior lines of therapy (median 2, range 1-4); 31 (38%) had rituximab refractory disease; 33 (41%) were refractory to the previous line of therapy, 43 (53%) had Ann Arbor stage ≥III disease; and 42 (52%) had an International Prognostic Index of 3-5 at study entry, indicating poor prognosis. The most common treatment-emergent adverse events (any grade/grade ≥3) were neutropenia in 39/35 (48%/43%) patients, thrombocytopenia in 26/14 (32%/17%), anemia in 25/7 (31%/9%), diarrhea in 24/1 (30%/1%), pyrexia in 18/1 (22%/1%) and asthenia in 16/2 (20%/2%) patients. Thirty-four (42%) patients required dose reduction with LEN, 58 (72%) patients overall could stay on a daily LEN dose of 20 mg or higher. Based on investigator assessments, complete and partial responses were observed in 27 (33%) and 20 (25%) patients, respectively, resulting in an ORR of 58%. A further 12 (15%) patients had stable disease. With a median follow-up of 12 months, the median PFS was 16.2 months (95% CI: 6.3-not reached [NR] ). Responses were durable with a median DoR not reached (95% CI: NR-NR) and 70% of responding patients were without progression at 12 months (Kaplan-Meier estimate). A significant proportion of patients (37/81; 46%) are still on study treatment, with 19 having been treated for over 12 months. Median OS has not been reached (95% CI: 18.6-NR); the 12-month OS rate was 73% (95% CI: 63-85). Conclusions: MOR208 in combination with LEN has shown highly encouraging activity in patients with R-R DLBCL who were ineligible for HDC and ASCT and who had a poor prognosis. These results indicate a significant improvement in outcome for these patients who have very limited treatment options. MOR208 plus LEN was well tolerated in this population, without evidence of additive toxicity. Treatment and follow-up are currently ongoing, as are cell of origin and other biomarker analyses. Disclosures Salles: Novartis: Consultancy, Honoraria; Epizyme: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Merck: Honoraria; Morphosys: Honoraria; Pfizer: Honoraria; Servier: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Acerta: Honoraria; AbbVie: Honoraria; Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding. González-Barca:Roche: Speakers Bureau; Celtrion: Consultancy; Gilead: Consultancy; janssen: Consultancy, Speakers Bureau. Jurczak:Pharmacyclics: Research Funding; MorphoSys: Research Funding; Merck: Research Funding; Nordic Nanovector: Research Funding; Janssen: Research Funding; Epizyme: Research Funding; Celgene: Research Funding; Beigene: Research Funding; Bayer: Research Funding; Afimed: Research Funding; Sandoz-Novartis: Consultancy; Janssen: Consultancy; European Medicines Agency: Consultancy; AstraZeneca: Consultancy; Acerta: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Servier: Research Funding; Roche: Research Funding; TG Therapeutics: Research Funding. Gaidano:Morphosys: Honoraria; AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Kalakonda:Celgene: Research Funding. Dreyling:Bayer: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Acerta: Consultancy; Roche: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sandoz: Consultancy. Zinzani:Janssen: Honoraria, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Honoraria, Speakers Bureau; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dirnberger-Hertweck:MorphoSys: Employment. Weirather:MorphoSys: Employment. Ambarkhane:MorphoSys: Employment. Maddocks:Pharmacyclics: Research Funding; Novartis: Research Funding; Pharmacyclics/Janssen: Honoraria; AstraZeneca: Honoraria; Teva: Honoraria; Merck: Research Funding; BMS: Research Funding.

Abstract: Background: Tafasitamab, an anti-CD19 immunotherapy that enhances antibody-dependent cellular cytotoxicity and phagocytosis, received accelerated approval in the USA and conditional authorization in Europe in combination with lenalidomide (LEN) for patients (pts) with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant (ASCT) based on the results of the open-label, multicenter, single-arm, Phase II L-MIND study (NCT02399085; Salles G, et al. Lancet Oncol 2020, Duell J, et al. Haematologica 2021). Here, we report the final, 5-year follow-up of L-MIND. Data cut-off was Nov 14, 2022. Methods: Pts were aged ≥18 years with ASCT-ineligible R/R DLBCL, 1-3 prior systemic therapies (including a CD20-targeting regimen), and ECOG PS 0-2. Tafasitamab (12 mg/kg) was given for up to 12 cycles in combination with LEN (25 mg), then as monotherapy until disease progression (PD) or unacceptable toxicity. The primary endpoint was best objective response rate (ORR; complete response [CR] or partial response [PR] , by independent radiology committee). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and incidence and severity of adverse events (AEs). Exploratory analyses evaluated efficacy endpoints by prior lines of therapy (pLoT). Results: Of 81 pts enrolled, 80 were treated (full analysis set [FAS]). The ORR (FAS) of 57.5% [95% CI: 45.9-68.5] , with CR of 41.2% [30.4-51.6] (n=33) and PR of 16.2% [8.9-26.2] (n=13), was generally consistent with the primary and 3-year analyses. Median DoR was not reached (NR) with median follow up (mFU) of 44.0 months [29.9-57.0]. Median PFS was 11.6 months [5.7-45.7] (mFU 45.6 [22.9-57.6]) and median OS was 33.5 months [18.3-NR] (mFU 65.6 [59.9-70.3]). At data cut-off, OS was & gt;60 months in 21 pts (18 with best response of CR, 1 PR, 1 stable disease and 1 PD), including 14 with 1 pLoT and 7 with ≥2 pLoT. Pts with 1 pLoT (n=40) in the FAS had higher ORR (67.5%; 52.5% CR [n=21] and 15% PR [n=6] ) compared to pts with ≥2 pLoT (n=40; 47.5%; 30% CR [n=12] and 17.5% PR [n=7] ). However, median DoR was not reached for both subgroups, indicating similar long-term efficacy for responders. AEs were consistent with previous reports and manageable; incidence declined after transition from combination to tafasitamab monotherapy and again with monotherapy & gt;2 years. Conclusion: The final, 5-year analysis of L-MIND showed prolonged durable responses with tafasitamab + LEN combination therapy, followed by long-term tafasitamab monotherapy, in pts with R/R DLBCL ineligible for ASCT, with median DoR not reached after 44 months mFU. No new safety signals were identified, confirming the tolerability profile observed with earlier data cuts. These long-term data suggest that this immunotherapy may have curative potential that is being explored in further studies. Citation Format: Johannes Duell, Pau Abrisqueta, Marc Andre, Marinela Augustin, Gianluca Gaidano, Eva González Barca, Wojciech Jurczak, Nagesh Kalakonda, Anna Marina Liberati, Kami J. Maddocks, Tobias Menne, Zsolt Nagy, Olivier Tournilhac, Abhishek Bakuli, Aasim Amin, Konstantin Gurbanov, Gilles Salles. Five-year efficacy and safety of tafasitamab in patients with relapsed or refractory DLBCL: Final results from the phase II L-MIND study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT022.

Abstract: Tafasitamab, an anti-CD19 immunotherapy, is used with lenalidomide for patients with autologous stem cell transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) based on the results of the phase II L-MIND study (NCT02399085). We report the final 5-year analysis. Eighty patients (≥18 years, 1–3 prior systemic therapies, ECOG PS 0–2) received co-administered tafasitamab and lenalidomide for up to 12 cycles, followed by tafasitamab monotherapy until disease progression (PD) or unacceptable toxicity. Primary endpoint was best objective response rate (ORR). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory analyses evaluated efficacy endpoints by prior lines of therapy (pLoT). At data cut-off on November 14, 2022, ORR was 57.5%, with complete response (CR) of 41.3% (n=33), which was consistent with prior analyses. With median follow-up (mFU) of 44.0 months, median DoR was not reached. Median PFS was 11.6 months [95% CI, 5.7–45.7] (mFU 45.6), and median OS was 33.5 months [95% CI, 18.3–NR] (mFU 65.6). Patients with 1 pLoT (n=40) showed higher ORR (67.5%; 52.5% CR) compared with patients with ≥2 pLoT (n=40; 47.5%; 30% CR), but median DoR was not reached in either subgroup. Other exploratory analyses revealed consistent long-term efficacy results across subgroups. Adverse events were consistent with previous reports and manageable, and their frequency decreased during tafasitamab monotherapy, with no new safety concerns. This final 5-year analysis of L-MIND demonstrates that this immunotherapy combination is well tolerated and has long-term clinical benefit with durable responses.