Wu, Xiaoling

8005 Background: CARTITUDE-1 (NCT03548207) is a phase 1b/2 study evaluating ciltacabtagene autoleucel (cilta-cel; JNJ-68284528), a CAR T-cell therapy with two BCMA–targeting single-domain antibodies, in patients (pts) with R/R MM. Here, we report updated results in pts with a longer duration (median 12.4 months) of follow-up. Methods: Eligible pts had MM and received ≥3 prior regimens or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), and had received a PI, IMiD, and anti-CD38 antibody. After apheresis, bridging therapy was permitted. Pts received a single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg; range 0.5-1.0×106) 5–7 days (d) after lymphodepletion (300 mg/m2 cyclophosphamide, 30 mg/m2 fludarabine daily for 3 d). The primary objectives were to characterize cilta-cel safety, confirm the recommended phase 2 dose (RP2D; phase 1b), and evaluate efficacy (phase 2). Cytokine release syndrome (CRS) was graded by Lee et al (Blood 2014) and neurotoxicity by CTCAE, v5.0 (in phase 1b). CRS and ICANS were graded by ASTCT criteria (in phase 2). Here, Lee et al and CTCAE v5.0 were mapped to ASTCT for CRS and ICANS, respectively. Results: As of Sept 1, 2020, 97 pts with a median of 6 prior lines received cilta-cel. Overall response rate per independent review committee (primary endpoint) was 97% (95% CI, 91–99), with 67% achieving stringent complete response (sCR). Median time to first response was 1 month (range, 1–9), and median time to CR or better was 2 months (range, 1–15). Responses deepened over time, and median duration of response was not reached. Of 57 pts evaluable for minimal residual disease (MRD) assessment, 93% were MRD-negative at 10-5. The 12-month progression-free survival (PFS) and overall survival rates (95% CI) were 77% (66–84) and 89% (80–94), respectively; median PFS was not reached. Grade 3/4 hematologic AEs ≥20% included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). CRS occurred in 95% of pts (4% grade 3/4), with median time to onset of 7 d (range, 1–12), and median duration of 4 d (range, 1–14, excluding 1 pt with 97-d duration). CRS resolved in all but one with grade 5 CRS/haemophagocytic lymphohistiocytosis. CAR T-cell neurotoxicity occurred in 21% of pts (grade ≥3, 10%). Fourteen deaths occurred during the study after cilta-cel infusion: none within the first 30 days, 2 within 100 days; and 12 more than 100 days post infusion, of which 5 were due to disease progression, and 4 due to treatment-related AEs. Conclusions: A single infusion of cilta-cel yielded early, deep, and durable responses in heavily pretreated pts with MM, with a manageable safety profile at the RP2D. Cilta-cel is under further investigation in other MM populations in earlier lines of therapy and in outpatient settings. Clinical trial information: NCT03548207.

Background: The phase 1b/2 CARTITUDE-1 study (NCT03548207) is evaluating ciltacabtagene autoleucel (cilta-cel; JNJ-68284528; LCAR-B38M CAR-T cells), a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed/refractory (R/R) multiple myeloma (MM). Cytokine release syndrome (CRS), a known side effect of CAR-T therapy, can be mild to life-threatening and requires careful monitoring and management. Here, we analyzed CRS and cytokine profiles in CARTITUDE-1. Methods: Eligible patients (aged ≥18 years) had a diagnosis of MM per International Myeloma Working Group criteria, measurable disease, Eastern Cooperative Oncology Group performance status ≤1, received ≥3 prior regimens or were double-refractory to a proteasome inhibitor and immunomodulatory drug, and received an anti-CD38 antibody. Bridging therapy was permitted after apheresis. At 5-7 days prior to cilta-cel infusion, lymphodepletion was performed with cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 days. Cilta-cel was administered as a single infusion at a target dose of 0.75×106 (range: 0.5-1.0×106) CAR+ viable T cells/kg. CRS was graded using Lee et al (Blood 2014) in the phase 1b portion and American Society for Transplantation and Cellular Therapy (ASTCT) in the phase 2 portion. In this combined analysis, Lee et al criteria were mapped to ASTCT criteria for patients in the phase 1b portion. Serum samples for cytokine profiling were collected prior to lymphodepletion, prior to cilta-cel infusion and 2 hours post-infusion on Day 1, at regular time points until Day 100, and if CRS was suspected or reported. Results: A total of 97 patients with R/R MM were treated with cilta-cel; median follow-up for this analysis was 8.8 months (range: 1.5-20.4). CRS was reported in 92 (94.8%) patients. A total of 48 (49.5%) patients had grade 1 CRS, 38 (39.2%) had grade 2, 4 (4.1%) had grade 3, and 1 had grade 5 (1.0%); maximum toxicity grade according to the ASTCT consensus grading system could not be derived for 1 patient with CRS in the phase 1b portion. Median time to CRS onset from cilta-cel infusion was 7.0 days (range: 1-12). Median duration of CRS was 4.0 days (range: 1-27, excluding n=1 with 97 days). Supportive measures to treat CRS or CRS symptoms were administered to 87 (89.7%) patients, most commonly tocilizumab (69.1%), acetaminophen (68.0%), corticosteroids (20.6%), and anakinra (18.6%). CRS resolved in 91 (98.9%) patients; the patient with grade 5 CRS/hemophagocytic lymphohistiocytosis died on Day 99 subsequent to sequelae of grade 4 CRS. Across all patients, levels of interleukin (IL)-6, IL-10, and interferon-γ peaked at Days 7-14 post-cilta-cel infusion. Conclusions: CRS after cilta-cel treatment was low grade and manageable in most patients with R/R MM. The low rate of grade ≥3 CRS, median time to CRS onset of 7.0 days, and median duration of 4.0 days suggests outpatient dosing of cilta-cel may be feasible; this approach is being explored in the phase 2 CARTITUDE-2 study (NCT04133636). Disclosures Lin: Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite, a Gilead Company: Consultancy, Research Funding; Vineti: Consultancy; Takeda: Research Funding; Merck: Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding. Martin:Janssen: Research Funding; AMGEN: Research Funding; Sanofi: Research Funding; Seattle Genetics: Research Funding; GSK: Consultancy. Cohen:Novartis: Other: Patents/Intellectual property licensed, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda,: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees. Jakubowiak:AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive, Juno: Consultancy, Honoraria. Usmani:Celgene: Other; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Research Funding; GSK: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Array Biopharma: Research Funding; Merck: Consultancy, Research Funding; Abbvie: Consultancy; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Incyte: Research Funding. Madduri:AbbVie: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Foundation Medicine: Consultancy, Honoraria; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau. Stewart:Janssen, BMS, Sanofi-Aventis, GSK: Honoraria; Tempus, Inc., Genomics England LLC: Membership on an entity's Board of Directors or advisory committees. Singh:Janssen: Current Employment. Zudaire:Janssen: Current Employment. Yeh:Janssen: Current Employment. Allred:Janssen: Current Employment. Olyslager:Janssen: Current Employment. Banerjee:Janssen: Current Employment. Goldberg:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Schecter:Janssen: Current Employment. Jackson:Memorial Sloan Kettering Cancer Center: Consultancy; Janssen: Current Employment. Deraedt:Janssen: Current Employment, Current equity holder in publicly-traded company. Geng:Legend Biotech USA Inc.: Current Employment. Wu:Legend Biotech USA Inc.: Current Employment. Carrasco:Legend Biotech USA Inc.: Current Employment. Akram:Legend Biotech USA Inc.: Current Employment. Hossain:Legend Biotech USA Inc.: Current Employment. Wang:Legend Biotech USA Inc.: Current Employment. Berdeja:CRISPR Therapeutics: Consultancy, Research Funding; EMD Sorono: Research Funding; Teva: Research Funding; Servier: Consultancy; Vivolux: Research Funding; Abbvie: Research Funding; Novartis: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Karyopharm: Consultancy; Kesios: Research Funding; Kite Pharma: Consultancy; Legend: Consultancy; Genentech, Inc.: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Cellularity: Research Funding; Constellation: Research Funding; Glenmark: Research Funding; CURIS: Research Funding; Bioclinica: Consultancy; Amgen: Consultancy, Research Funding; Bluebird: Research Funding; Poseida: Research Funding; Acetylon: Research Funding; Prothena: Consultancy; Lilly: Research Funding. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy.

Background: Multiple myeloma (MM) negatively affects health-related quality of life (HRQoL), and with each relapse, patients with MM experience further declines in HRQoL. Patient-reported HRQoL is therefore an important treatment outcome, in addition to clinical response to therapy. CARTITUDE-1 (NCT03548207) is a phase 1b/2 study evaluating the safety and efficacy of ciltacabtagene autoleucel (cilta-cel; JNJ-68284528; LCAR-B38M CAR-T cells), a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed/refractory (R/R) MM. We evaluated symptoms, functioning, and overall HRQoL through patient-reported outcome measures, which is a secondary objective of CARTITUDE-1. Methods: Patients were ≥18 years of age with a diagnosis of MM per International Myeloma Working Group criteria, measurable disease, and Eastern Cooperative Oncology Group performance status ≤1. Patients had received ≥3 prior regimens for MM or were double-refractory to a proteasome inhibitor and immunomodulatory drug, and had received an anti-CD38 antibody. Cilta-cel was given as a single infusion on Day 1 (target dose: 0.75×106 [range: 0.5-1.0×106] CAR+ viable T cells/kg) 5-7 days after start of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days). In the phase 2 portion of CARTITUDE-1, HRQoL was assessed at baseline, on Days 7, 28, 56, 78, and 100, and every 28 days thereafter using 3 patient-reported instruments: the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30), 4 items from the EORTC QLQ-Multiple Myeloma (MY20) module, and the 5-level EuroQol Five Dimension (EQ-5D-5L) measure. Raw EORTC QLQ-C30 and EORTC QLQ-MY20 scores were linearly transformed to a scale ranging from 0 to 100; the EQ-5D-5L visual analog scale (VAS) score ranges from 0 to 100. Clinically meaningful changes in EORTC QLQ-C30 symptoms, physical functioning, and overall HRQoL were based on anchor-based methods using a patient global impression of change item. Repeated-measures mixed-effects models were used to analyze mean changes in HRQoL from baseline to subsequent assessment time points in patients in the modified intent-to-treat population with ≥1 post-baseline assessment. Median time to event of HRQoL scores was calculated descriptively, using a change in score ≥0.5×standard deviation of values prior to cilta-cel infusion as improvement/worsening with death due to progression defined as worsening. Results: For the 68 patients in the phase 2 portion of CARTITUDE-1 (63.2% male; median age: 62.0 years [range: 43-78]), questionnaire completion rates at baseline and Day 100, respectively, were 92.6% and 69.2% for both the EORTC QLQ-C30 and EORTC QLQ-MY20 items and 92.6% and 70.8% for the EQ-5D-5L. For EORTC QLQ-C30 subscales, clinically meaningful improvements at Day 100 were seen for 71.1% of patients for pain, 62.2% for fatigue, 72.1% for physical functioning, and 51.1% for global health status. Mean changes in pain and fatigue showed a reduction in these symptoms over time (following an initial worsening of fatigue at Day 7; Figure). This trend of improvements over time was also observed for overall HRQoL and EORTC QLQ-MY20 single items. Clinically meaningful improvements at Day 100, defined by a literature-based minimal important difference of 10 points in mean score, were observed for the EORTC QLQ-MY20 single items: thinking about illness and worries about dying or future health. Approximately 50% of the population reported an event of improvement or worsening in EORTC QLQ-C30 and EQ-5D-5L scales, with the rest censored in this early data cut; among these patients, median time to improvement was approximately 1-2 months (with median time to worsening occurring less than 1 month after cilta-cel treatment). There was a trend for an improvement in mean EORTC QLQ-C30 global health status, physical functioning, pain, and fatigue, and EQ-5D-5L VAS at Day 100 with increased depth of response. Conclusions: Some patients with heavily pretreated MM showed rapid and clinically meaningful improvements in pain, fatigue, physical functioning, overall HRQoL, and future perspectives, consistent with their clinical outcomes. With additional follow-up, it is possible that these early improvements in symptoms will translate into greater improvement in overall HRQoL in the long term. Disclosures Martin: Janssen: Research Funding; Sanofi: Research Funding; AMGEN: Research Funding; Seattle Genetics: Research Funding; GSK: Consultancy. Lin:Vineti: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Legend BioTech: Consultancy; Bluebird Bio: Consultancy, Research Funding; Juno: Consultancy; Merck: Research Funding; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cohen:Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda,: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Patents/Intellectual property licensed, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees. Htut:City of Hope Medical Center: Current Employment. Stewart:Janssen, BMS, Sanofi-Aventis, GSK: Honoraria; Tempus, Inc., Genomics England LLC: Membership on an entity's Board of Directors or advisory committees. Hari:GSK: Consultancy; BMS: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Incyte Corporation: Consultancy; Janssen: Consultancy. Berdeja:Teva: Research Funding; Cellularity: Research Funding; Kesios: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; CURIS: Research Funding; EMD Sorono: Research Funding; Genentech, Inc.: Research Funding; Karyopharm: Consultancy; Poseida: Research Funding; Novartis: Research Funding; Lilly: Research Funding; Amgen: Consultancy, Research Funding; Acetylon: Research Funding; Glenmark: Research Funding; Janssen: Consultancy, Research Funding; Vivolux: Research Funding; Takeda: Consultancy, Research Funding; Servier: Consultancy; CRISPR Therapeutics: Consultancy, Research Funding; Constellation: Research Funding; Bluebird: Research Funding; Abbvie: Research Funding; Prothena: Consultancy; Bioclinica: Consultancy; Kite Pharma: Consultancy; Legend: Consultancy. Madduri:Foundation Medicine: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; AbbVie: Consultancy, Honoraria; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Celgene: Consultancy, Honoraria. Usmani:Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Incyte: Research Funding; Pharmacyclics: Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; GSK: Consultancy, Research Funding; Abbvie: Consultancy; Array Biopharma: Research Funding; Celgene: Other; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding. Yeh:Janssen: Current Employment. Allred:Janssen: Current Employment. Olyslager:Janssen: Current Employment. Banerjee:Janssen: Current Employment. Goldberg:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Schecter:Janssen: Current Employment. Jackson:Janssen: Current Employment; Memorial Sloan Kettering Cancer Center: Consultancy. Deraedt:Janssen: Current Employment, Current equity holder in publicly-traded company. Gries:Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau:Janssen: Current Employment, Current equity holder in publicly-traded company. Wu:Legend Biotech USA Inc.: Current Employment. Carrasco:Legend Biotech USA Inc.: Current Employment. Akram:Legend Biotech USA Inc.: Current Employment. Hossain:Legend Biotech USA Inc.: Current Employment. Jakubowiak:AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive, Juno: Consultancy, Honoraria. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy.

Background: Ciltacabtagene autoleucel (cilta-cel; JNJ-68284528; LCAR-B38M CAR-T cells) is a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity. In the phase 1 LEGEND-2 study in China, LCAR-B38M yielded deep, durable responses with a manageable safety profile in patients (pts) with relapsed/refractory multiple myeloma (R/R MM). The phase 1b/2 CARTITUDE-1 study (NCT03548207) is further evaluating cilta-cel in this pt population in the US. We present updated data from the phase 1b portion along with initial phase 2 data. Methods: Eligible pts (aged ≥18 y) were diagnosed with MM per International Myeloma Working Group (IMWG) criteria and had measurable disease, Eastern Cooperative Oncology Group performance status ≤1, received ≥3 prior regimens or were double-refractory to a proteasome inhibitor and immunomodulatory drug, and received an anti-CD38 antibody. After apheresis, bridging therapy was permitted. Cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 d were used for lymphodepletion. A single infusion of cilta-cel at a target dose of 0.75×106 (range 0.5-1.0×106) CAR+ viable T cells/kg was administered 5-7 d after start of lymphodepletion. The primary objective of the phase 1b portion was to characterize cilta-cel safety and establish the recommended phase 2 dose; the primary objective of the phase 2 portion was to evaluate cilta-cel efficacy. Response was assessed per IMWG criteria and minimal residual disease (MRD) by next-generation sequencing. Adverse events (AEs) were graded using CTCAE v5.0. In the phase 1b portion, cytokine release syndrome (CRS) was graded by Lee et al (Blood 2014) and neurotoxicity by CTCAE v5.0; in the phase 2 portion, CRS and neurotoxicity were graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria. In this combined analysis, Lee et al and CTCAE v5.0 were mapped to ASTCT criteria for CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), respectively. Results: As of the May 20, 2020 clinical cutoff, 97 pts (58.8% male; median age 61.0 y [range 43-78]) with R/R MM received cilta-cel (29 in phase 1b; 68 in phase 2). Median follow-up duration was 8.8 mo (range 1.5-20.4). Pts had received a median of 6 prior lines of therapy (range 3-18); 83.5% were penta-exposed, 87.6% were triple-refractory, 41.2% were penta-refractory, and 97.9% were refractory to last line of therapy. Overall response rate per independent review committee (primary endpoint) was 94.8% (95% CI 88.4-98.3), with a stringent complete response rate of 55.7% (95% CI 45.2-65.8), very good partial response rate of 32.0% (95% CI 22.9-42.2), and partial response rate of 7.2% (95% CI 3.0-14.3). All pts achieved a reduction in M-protein. Median time to first response was 1.0 mo (range 0.9-5.8; 80.4% ≤1.0 mo), and median time to complete response or better was 1.8 mo (range 0.9-12.5; 74.1% ≤3.0 mo); responses deepened over time (Figure). Median duration of response was not reached (NR). Of 52 MRD-evaluable pts, 94.2% were MRD-negative at 10-5. The 6-mo progression-free survival (PFS) and overall survival (OS) rates (95% CI) were 87.4% (78.9-92.7) and 93.8% (86.7-97.2), respectively; median PFS and OS were NR. Ten deaths occurred during the study; 8 were due to AEs (both related and unrelated; CRS/hemophagocytic lymphohistiocytosis, neurotoxicity, respiratory failure, sepsis, septic shock, pneumonia, lung abscess, and acute myelogenous leukemia [n=1 each]), and 2 due to progressive disease. AEs reported in >70% of pts were CRS (94.8%; grade [gr] 3/4 4.1%), neutropenia (90.7%; gr 3/4 90.7%), anemia (81.4%; gr 3/4 68.0%), and thrombocytopenia (79.4%; gr 3/4 59.8%). Median time to CRS onset was 7.0 d (range 1-12) and median duration 4.0 d (range 1-27, excluding n=1 with 97 d). CAR-T cell-related neurotoxicity was reported in 20.6% of pts (gr 3/4 10.3%). Cilta-cel CAR+ T cells showed maximum peripheral expansion at 14 d (range 9-43). Among pts with 6 mo' individual follow-up, 67% had cilta-cel CAR+ T cells below the level of quantification (2 cells/µL) in peripheral blood. Conclusions: Preliminary phase 1b/2 data from CARTITUDE-1 indicate a single low-dose infusion of cilta-cel leads to early, deep, and durable responses in heavily pretreated pts with MM with a safety profile consistent with LEGEND-2. Further investigation of cilta-cel in other MM populations is underway. Disclosures Madduri: Celgene: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Foundation Medicine: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau. Berdeja:Teva: Research Funding; Bluebird: Research Funding; Bioclinica: Consultancy; Celgene: Consultancy, Research Funding; EMD Sorono: Research Funding; Kite Pharma: Consultancy; Prothena: Consultancy; Cellularity: Research Funding; Karyopharm: Consultancy; Servier: Consultancy; Legend: Consultancy; Poseida: Research Funding; Lilly: Research Funding; Acetylon: Research Funding; CURIS: Research Funding; Janssen: Consultancy, Research Funding; Genentech, Inc.: Research Funding; Glenmark: Research Funding; Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Constellation: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Vivolux: Research Funding; Abbvie: Research Funding; Amgen: Consultancy, Research Funding; Kesios: Research Funding; Novartis: Research Funding. Usmani:Celgene: Other; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; GSK: Consultancy, Research Funding; Pharmacyclics: Research Funding; Merck: Consultancy, Research Funding; Abbvie: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Incyte: Research Funding; Array Biopharma: Research Funding; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding. Jakubowiak:Adaptive, Juno: Consultancy, Honoraria; AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cohen:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda,: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Other: Patents/Intellectual property licensed, Research Funding. Stewart:Janssen, BMS, Sanofi-Aventis, GSK: Honoraria; Tempus, Inc., Genomics England LLC: Membership on an entity's Board of Directors or advisory committees. Hari:Amgen: Consultancy; BMS: Consultancy; GSK: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Incyte Corporation: Consultancy. Htut:City of Hope Medical Center: Current Employment. Munshi:OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Consultancy; Janssen: Consultancy; Adaptive: Consultancy; Legend: Consultancy; Amgen: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; AbbVie: Consultancy; C4: Current equity holder in private company. Deol:Novartis: Consultancy; Kite, a Gilead Company: Consultancy. Lesokhin:BMS: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Janssen: Research Funding; Juno: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; GenMab: Consultancy, Honoraria. Singh:Janssen: Current Employment. Zudaire:Janssen: Current Employment. Yeh:Janssen: Current Employment. Allred:Janssen: Current Employment. Olyslager:Janssen: Current Employment. Banerjee:Janssen: Current Employment. Goldberg:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Schecter:Janssen: Current Employment. Jackson:Janssen: Current Employment; Memorial Sloan Kettering Cancer Center: Consultancy. Deraedt:Janssen: Current Employment, Current equity holder in publicly-traded company. Zhuang:Janssen: Current Employment. Infante:Janssen: Current Employment. Geng:Legend Biotech USA Inc.: Current Employment. Wu:Legend Biotech USA Inc.: Current Employment. Carrasco:Legend Biotech USA Inc.: Current Employment. Akram:Legend Biotech USA Inc.: Current Employment. Hossain:Legend Biotech USA Inc.: Current Employment. Rizvi:Legend Biotech USA Inc.: Current Employment. Fan:Legend Biotech USA Inc.: Current Employment. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. Lin:Kite, a Gilead Company: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Merck: Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Vineti: Consultancy; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees. Martin:AMGEN: Research Funding; Seattle Genetics: Research Funding; Janssen: Research Funding; GSK: Consultancy; Sanofi: Research Funding.

8522 Background: CC-223 is an ATP-competitive inhibitor of the mTOR kinase, including both TORC1 and TORC2 complexes. CC-223 was selected to address resistance of rapamycin analogues mediated by TORC2 activation. Methods: Following establishment of the MTD (reported at ASCO 2012), subjects with advanced DLBCL, MM and select solid tumors were enrolled in parallel expansion cohorts of up to 20 evaluable subjects. CC-223 was dosed at 45 mg once daily in 28 day cycles until disease progression. Results: As of 09 January, 2013, 35 subjects were enrolled including DLBCL (21) and MM (14). Results in solid tumor cohorts are reported separately. The most common (> 20%) related adverse events (all grades) were fatigue, hyperglycemia, rash, anorexia, nausea, vomiting and diarrhea. In addition, related serious adverse events included infection (2), pneumonitis (1), renal insufficiency (2), pancreatitis (1) and thrombocytopenia (1). CC-223 dose reduction was required in 9 subjects (27%), usually during cycle 1 or 2, and 4 additional subjects with DLBCL dropped out during cycle 1 due to toxicity. Systemic exposure was similar between the two tumor cohorts and was associated with inhibition of TORC1 (p4EBP1) and TORC2 (pAKT) biomarkers in blood cells. Reduction in glucose uptake (32 – 98% decrease) on PET imaging at day 15 was observed in 7/7 DLBCL subjects with results currently available. Three of 17 evaluable subjects with DLBCL had partial responses (PR) after 2 cycles; two with rapid and near complete regression (> 90%) of target lesions by CT and PET with PR confirmed and treatment ongoing at 6 and 8 cycles. Both had failed multiple prior treatment regimens (5 and 3, respectively), including autologous stem cell transplant (ASCT). No responses were observed in 10/14 evaluable subjects with MM although 2 subjects have prolonged stable disease (SD) with treatment ongoing at 12 and 14 cycles. Conclusions: Encouraging signals of biomarker and clinical activity were observed in DLBCL, including two near complete responses, which are ongoing. Due to dose reductions and interruptions, a starting dose of 30 mg QD is recommended for future studies. Clinical trial information: NCT01177397.