Introduction: Diffuse large B-cell lymphoma (DLBCL) represents 33% of the non-Hodgkin lymphomas (NHL) and expresses CD19, a classic B-cell marker found on B lymphocytes. ADCT-402 (loncastuximab tesirine; Lonca-T) is an antibody drug conjugate comprising a humanized antibody directed against human CD19 conjugated to a pyrrolobenzodiazepine dimer toxin. This first-in-human clinical study evaluated the safety and efficacy of Lonca-T in patients (pts) with relapsed/refractory (R/R) B-cell lineage NHL. Here we present interim results in the subgroup of pts with DLBCL. Interim efficacy and safety of Lonca-T in pts with follicular lymphoma and mantle cell lymphoma are presented in a separate abstract. Methods: Pts ≥18 years of age with R/R DLBCL who have failed or are intolerant to established therapies, or have no other treatment options available, were enrolled in this Phase 1, multicenter, open-label, single-arm study, including dose-escalation and dose-expansion parts. The primary objectives are to evaluate the safety and tolerability of Lonca-T, and determine the recommended dose(s) to use for expansion cohorts. The secondary objectives are to evaluate the clinical activity (measured by overall response rate [ORR], duration of response [DoR], progression-free survival [PFS] and overall survival [OS]), pharmacokinetics, pharmacodynamics, and anti-drug antibody activity. Pts receive 1-hour intravenous infusions of Lonca-T every 3 weeks (1 cycle), with a 3+3 dose-escalation design for the dose-escalation part of the study. No intra-pt dose escalation is allowed. Results: As of June 20, 2018, 183 pts had been enrolled on the study, including 137 with DLBCL (79 male, 58 female). Pts with DLBCL had a median age of 63 years [range 20-86], and had received a median of 3 previous therapies (range 1-10; Table). Pts received doses of Lonca-T ranging from 15 to 200 µg/kg (median cycles: 2 [range 1-13]). Treatment-emergent adverse events (TEAEs) were reported in 136/137 (99.3%) pts, and grade ≥3 TEAEs in 100/137 (73.0%) pts. The most common all-grade TEAEs (≥20% pts), regardless of relationship to study treatment, were fatigue (57 [41.6%]), nausea (44 [32.1%], peripheral edema (44 [32.1%]), anemia (39 [28.5%]), rash (35 [25.5%]), gamma-glutamyltransferase (GGT) increased (33 [24.1%]), constipation (30 [21.9%]), dyspnea (29 [21.2%]), and thrombocytopenia (28 [20.4%]). The most common grade ≥3 TEAEs (>10% pts) were GGT increased (21 [15.3%]), neutropenia (20 [14.6%]), neutrophil count decreased (19 [13.9%]), anemia (15 [10.9]), thrombocytopenia (15 [10.9%]) and platelet count decreased (14 [10.2%]. Approximately 66% and 72% of pts in the 120 and 150 µg/kg groups, respectively, tolerated at least 2 cycles before any AE leading to dose reduction/delay occurred. The figure depicts tumor response data. Out of 132 evaluable pts with DLBCL, the ORR was 40.2% (53/132 pts), comprising 29/132 (22.0%) complete responses (CRs) and 24/132 (18.2%) partial responses (PRs). Median DoR was 4.17 months and PFS was 2.79 months after a median follow-up of 5.13 months. Median DoR was not reached in pts achieving a CR and was 2.76 months in pts with a PR. In pts with non-bulky disease, the ORR was 44.2% (50/113 pts); 28/113 (24.8%) pts attained a CR and 22/113 (19.5%) pts attained a PR. The majority of pts (122/132) received doses ≥120 µg/kg; in these pts, the ORR was 41.8% (51/122 pts), with 28/122 (23.0%) pts attaining a CR and 23/122 (18.9%) pts attaining a PR. Conclusions: In this Phase 1 study, Lonca-T has demonstrated encouraging and durable single-agent antitumor activity and manageable toxicity in pts with R/R DLBCL at doses ≥120 µg/kg. Updated safety, tolerability, and efficacy results will be presented at the meeting. Study sponsored by ADC Therapeutics. http://clinicaltrials.gov/show/NCT02669017. Disclosures Radford: Pfizer: Research Funding; ADC Therapeutics: Consultancy, Research Funding; BMS: Consultancy, Speakers Bureau; GlaxoSmithKline: Equity Ownership; Seattle Genetics: Consultancy, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; AstraZeneca: Equity Ownership; Novartis: Consultancy, Speakers Bureau; Celgene: Research Funding. Kahl:Seattle Genetics: Consultancy; Genentech: Consultancy; ADC Therapeutics: Research Funding. Hamadani:Sanofi Genzyme: Research Funding, Speakers Bureau; Takeda: Research Funding; Cellerant: Consultancy; Ostuka: Research Funding; MedImmune: Consultancy, Research Funding; ADC Therapeutics: Research Funding; Janssen: Consultancy; Celgene Corporation: Consultancy; Merck: Research Funding. Carlo-Stella:Boehringher Ingelheim Italia: Consultancy; Bristol-Myers Squibb: Speakers Bureau; Sanofi: Consultancy; MSD Italia: Speakers Bureau; Rhizen Pharmaceuticals: Research Funding; Genenta Science: Speakers Bureau; Janssen: Speakers Bureau; AstraZeneca: Speakers Bureau; Amgen: Speakers Bureau; ADC Therapeutics: Research Funding, Speakers Bureau. Caimi:Genentech: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Kite Pharma: Membership on an entity's Board of Directors or advisory committees. Ardeshna:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Conference expenses, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees. Feingold:ADC Therapeutics: Employment, Equity Ownership. He:ADC Therapeutics: Employment, Equity Ownership. Reid:AbbVie: Research Funding; Millenium Pharmaceuticals: Research Funding; ADC Therapeutics: Research Funding. Solh:ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Amgen: Speakers Bureau. Chung:ADC Therapeutics: Research Funding. Heffner:Pharmacyclics: Research Funding; ADC Therapeutics: Research Funding; Kite Pharma: Research Funding; Genentech: Research Funding. Ungar:ADC Therapeutics: Employment, Equity Ownership. O'Connor:ADC Therapeutics: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding.

median prior lines of therapy was 3 (range 1-13), and 86% pts were refractory to prior therapy. CRS (according to the criteria by Lee et al.Blood 2014) occurred in 45 patients (23% G1, 24% G2, 3% G3, 1% G4). At the highest dose cohort (25 mg) >G3 CRS occurred in 3/8 pts at cycle 1, thereby preventing further dose escalation. One patient in the 25 mg cohort died of upper GI bleeding after an episode of severe CRS. All other CRS events were manageable and resolved, and patients were retreated without delay at the same dose at cycle 2, where only one additional CRS event was seen (G1).In the efficacy evaluable pts (n=84) the ORR and CR rate by investigator assessment (Lugano 2014 criteria) in aNHL (n=76) was 46% and 29%, and in FL (n=8) 63% and 50%, respectively. In the highest dose cohorts (10-25 mg) the ORR and CR rate in aNHL (n=38) was 55% and 37% indicating a dose-response relationship. CR was usually achieved at the first or second response assessments (C3 or C6) although in 4 aNHL pts late conversion from PR or SD to CR was observed at cycle 12. A patient with FL initially dosed at 15 μg who had progressed was retreated at 10 mg, achieving CR. After a median follow up of 3.8 months all but 2 CRs are still ongoing. Responses were seen across NHL subtypes and across prognostic factors such as disease burden, prior lines of therapy, and refractoriness to prior therapy. CD20-TCB exposure and receptor occupancy increased dosedependently across the investigated dose range. No anti-drugantibodies have been found. Mode of action was demonstrated by rapid and sustained T cell activation in peripheral blood and tumor biopsies.Conclusions: CD20-TCB is a novel 2:1 format T-cell-engaging bispecific antibody which displays highly promising clinical activity in heavily-pretreated NHL. ABSTRACT 93 Introduction: Diffuse large B-cell lymphoma (DLBCL) accounts for approximately one-third of non-Hodgkin lymphomas (NHL) and expresses CD19, a B-cell marker. Loncastuximab tesirine (Lonca) 94 ABSTRACT comprises a humanized anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer toxin. A first-in-human study of Lonca in patients (pts) with relapsed/refractory (R/R) B-cell NHL demonstrated encouraging and durable single-agent antitumor activity and manageable toxicity at doses ≥120 μg/kg in pts with R/R DLBCL. Here we present subgroup analyses of response in R/R DLBCL. Methods: Pts ≥18 years of age with R/R B-cell NHL were enrolled in this phase 1 study (NCT02669017). Analyses of treatment-emergent adverse events (TEAE), overall response rate (ORR) by demographic and clinical characteristics, and duration of response (DoR) by response to prior therapy were performed in pts with DLBCL receiving ≥120 μg/kg Lonca. Results: As of data cutoff (October 16, 2018), 129 pts with DLBCL had received Lonca at ≥120 μg/kg; 129 and 127 pts were evaluable for safety and efficacy, respectively. The most common TEAEs, regardless of relationship to Lonca, were fatigue (42.6%), peripheral edema (34.1%), and nausea (34.1%). The most common g...

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