Mawad, Raya

Background HPN217 is a B Cell Maturation Antigen (BCMA)-targeting tri-specific T cell engager (TCE). HPN217 contains three binding domains including anti-BCMA for MM cell binding, anti-albumin for half-life extension, and anti-CD3 for T cell engagement and activation. HPN217 is a small (~50 kDa) globular protein, designed to increase the therapeutic window by minimizing off-target toxicities and cytokine release syndrome (CRS). HPN217 is under investigation in patients (pts) with heavily pretreated relapsed/refractory MM (RRMM). Methods This study is designed to assess the safety, pharmacology and early clinical activity of HPN217 using fixed and step-dose (prime dose followed by target doses) regimens in dose escalation cohorts along with expansion of selected regimens for further evaluation. Pts with RRMM who have received at least 3 prior therapies including a proteasome inhibitor, an immunomodulatory drug, and CD38-targeted therapy are eligible. Prior exposure to a BCMA-targeting agent is permitted. Primary objectives include evaluation of safety, tolerability, pharmacokinetics (PK), and determination of the Recommended Phase 2 Dose(s) (RP2D). Secondary objectives include preliminary efficacy. HPN217 is administered IV once weekly or once every 2 weeks. Adverse events (AEs) are graded by CTCAE 5.0, and ASTCT for cytokine release syndrome (CRS) and ICANS. Clinical activity is assessed per IMWG Response Criteria. Results Dose escalation has been completed. 97 pts were enrolled across 15 dose escalation cohorts and expansion of 3 regimens with the highest target dose levels from dose escalation (12mg weekly; 24mg every 2 weeks; 24mg weekly for 1 cycle followed by 24mg every 2 weeks). As of 26 June 2023, across all cohorts, 94 pts were treated and had received a median (range) of 6 (2-19) prior lines of treatment (62% penta-exposed, 17% BCMA-targeted therapy, 68% prior transplantation). Median age was 70 (38-85) years. 36 pts (38%) remain on treatment. The most common (≥25%) treatment-emergent adverse events (TEAEs) across all cohorts and in the 12mg and 24mg cohorts are summarized in Table 1. Dose limiting toxicities (DLTs) of reversible transaminitis (Gr 3, n=1; Gr 4, n=1) in 2 pts at 2.86 mg fixed dose during dose escalation informed the choice of 2.15 mg as priming dose in the highest step dose cohorts; a maximum tolerated dose (MTD) has not been reached in step dose cohorts. All CRS events were grade 1-2 except one event of grade 3 CRS at 24 mg. Grade 1 ICANS was reported in 2 pts. Responses were observed at doses ≥ 2.15 mg. Among the 12mg and 24mg cohorts, 55% (22/40) of efficacy-evaluable pts currently have had a confirmed response (PR or better) including 2 pts with prior BCMA directed CAR-T cell therapy; disease assessments for recently enrolled patients are pending. Among pts with a response, 73% (16/22) have had a confirmed response of VGPR or better. Across all dose levels, the median time on treatment for pts with a confirmed response was 40 weeks (range 8.3-114 weeks), including 9 patients on treatment for over 12 months, with data maturing to include longer follow-up on patients recently enrolled. HPN217 exhibited linear and dose proportional PK across all dose groups with a median half-life of 68 hours (range 26-197 hours). Transient cytokine increases were higher with the initial/priming dose compared to subsequent/target doses. Conclusions Dose escalation of HPN217, a novel half-life extended BCMA-targeting T-cell engager, has been completed; the MTD was not reached in step dose cohorts. The 12mg and 24mg target doses are well tolerated with manageable adverse event profiles similar to those at lower dose levels and are associated with robust and durable clinical responses. Additional follow up of recently enrolled pts in 12 mg and 24 mg cohorts will inform the choice of the RP2D(s), and complete data on all pts enrolled will be presented. NCT04184050

Abstract Acute myeloid leukemia (AML), an aggressive malignancy with unmet medical need, lacks immunotherapeutic options. CD123, the cellular receptor for interleukin-3, expressed in AML is an attractive target for tumor-specific therapy. Vibecotamab (XmAb14045), a humanized bispecific antibody, monovalently binds both CD3 and CD123 to recruit cytotoxic T cells to kill CD123+ tumor cells. This phase 1 study’s primary objectives were safety and tolerability and identification of a maximum tolerated dose/recommended dose for use as monotherapy in patients with relapsed/refractory AML. Identification of a recommended phase 2 vibecotamab dose comprised 3 step-up doses (Week 1), which were noted to reduce cytokine response syndrome (CRS), followed by weekly dosing (1.7 μg/kg, Cohort -1D). In 16 of 120 patients, at least 1 treatment-emergent adverse event was classified as a dose-limiting toxicity. CRS, the most common adverse event (59.2%), managed with premedication, were mostly ≤grade 2. A secondary objective was assessment of efficacy in patients with CD123-expressing leukemias. A total of 10 of 111 (9.0%) efficacy-evaluable patients with AML achieved an overall response of morphologic leukemia-free state or better with an overall objective response rate (ORR) of 9.0%. Response was only observed in patients receiving a target dose of 0.75 μg/kg or higher (n = 87) in which the efficacy-evaluable ORR was 11.5%. Response was associated with lower baseline blast counts in blood and bone marrow (<25%) suggesting potential benefit. This trial was registered at www.clinicaltrials.gov as #NCT02730312.

Abstract ZUMA-3 is a phase 1/2 study evaluating KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We report the phase 1 results. After fludarabine-cyclophosphamide lymphodepletion, patients received a single infusion of KTE-X19 at 2 × 106, 1 × 106, or 0.5 × 106 cells per kg. The rate of dose-limiting toxicities (DLTs) within 28 days after KTE-X19 infusion was the primary end point. KTE-X19 was manufactured for 54 enrolled patients and administered to 45 (median age, 46 years; range, 18-77 years). No DLTs occurred in the DLT-evaluable cohort. Grade ≥3 cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 31% and 38% of patients, respectively. To optimize the risk-benefit ratio, revised adverse event (AE) management for CRS and NEs (earlier steroid use for NEs and tocilizumab only for CRS) was evaluated at 1 × 106 cells per kg KTE-X19. In the 9 patients treated under revised AE management, 33% had grade 3 CRS and 11% had grade 3 NEs, with no grade 4 or 5 NEs. The overall complete remission rate correlated with CAR T-cell expansion and was 83% in patients treated with 1 × 106 cells per kg and 69% in all patients. Minimal residual disease was undetectable in all responding patients. At a median follow-up of 22.1 months (range, 7.1-36.1 months), the median duration of remission was 17.6 months (95% confidence interval [CI], 5.8-17.6 months) in patients treated with 1 × 106 cells per kg and 14.5 months (95% CI, 5.8-18.1 months) in all patients. KTE-X19 treatment provided a high response rate and tolerable safety in adults with R/R B-ALL. Phase 2 is ongoing at 1 × 106 cells per kg with revised AE management. This trial is registered at www.clinicaltrials.gov as #NCT02614066.

Background: Blasts and leukemic stem cells of acute myeloid leukemia (AML) as well as several other hematologic malignancies express CD123, potentially providing a target for novel therapies. Vibecotamab (XmAb14045, SQZ622) is a potent bispecific antibody targeting both CD123 and CD3 that stimulates targeted T cell-mediated killing of CD123-expressing cells, regardless of T cell antigen specificity. It is a full-length immunoglobulin molecule designed to be dosed intermittently. Methods: Patients with relapsed or refractory AML, B-cell acute lymphoblastic leukemia (B-ALL), blast phase chronic myelogenous leukemia, or blastic plasmacytoid dendritic cell neoplasm were eligible to enroll on this first-in-human, multicenter, open-label phase 1 dose-escalation study (XmAb14045-01) with standard 3+3 design. The primary objective was to estimate the maximum tolerated dose (MTD) or recommended dose and schedule of vibecotamab. Secondary objectives included safety, preliminary antileukemic activity, and pharmacokinetics/pharmacodynamics of vibecotamab. Treatment was administered weekly in 28-day cycles, using a weight-based dose with 3 escalating doses in the first week followed by escalating weekly doses. Therapy was continued for as long as tolerated and there was continuing evidence of therapeutic benefit in the opinion of the investigator. Treatment response was assessed by the 2017 European LeukemiaNet (ELN) criteria after Cycle 1 and after each odd-numbered cycle. CRS was graded using the CRS revised grading system (Lee et al., Blood, 2014). Results: At data cut-off, 104 patients with AML, 1 with B-cell ALL, and 1 with CML as their primary diagnosis have been treated at dosages from 0.003 to 12.0 µg/kg vibecotamab. Patients had a median age of 63 years and were heavily pretreated (median of 3 prior therapies [range 1-8], including 32 (30%) who had undergone prior allogeneic stem cell transplantation). The recommended initial priming dose is 0.75 µg/kg; no MTD has been identified. CRS or its component symptoms was the most common treatment-emergent adverse event (TEAE). CRS occurred in 62 of 106 patients (85% grade 1-2, 15% grade ≥3), the majority on the first dose. Additional events consistent with CRS or infusion related reaction were seen in 24% of subjects (chills, fever, tachycardia, hypotension, etc.), and they were mostly mild or moderate severity. No myelosuppression requiring dose modification or evidence of tumor lysis syndrome was seen. Response of CR (2), CRi (3) or MLFS (2) was observed in 7/51 patients (ORR=14%) treated at higher dose levels (0.75 µg/kg). Stable Disease was observed in an additional 36 patients (71%). No CR, CRi, or morphologic leukemia-free state (MLFS) responses were observed at lower doses. Antileukemic activity occurred quickly; 6 out of 7 responders achieved at least a MLFS response after first cycle. A characterization of responders versus non-responders revealed responding patients harbor a lower burden of disease and specific T-cell subtypes. No association was found between response status and CD123 target expression on AML blasts. Conclusions: Vibecotamab demonstrated evidence of antileukemic activity in heavily pretreated patients with relapsed/refractory AML treated at the ≥0.75 µg/kg doses cohorts, with a 14% response rate. CRS was the most common toxicity but was generally manageable with premedications. The study is ongoing with further optimization of dose and schedule. Biomarker data suggest a population of AML patients that are more likely to respond. Additional information will be provided at the time of the meeting. Disclosures Ravandi: Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Orsenix: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Xencor: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Macrogenics: Research Funding. Stock:Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria; American Society of Hematology: Honoraria; Leukemia and Lymphoma Society: Research Funding; Novartis: Research Funding; Abbvie: Honoraria, Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; UpToDate: Honoraria. Foran:Xencor: Research Funding; H3Biosciences: Research Funding; Agios: Honoraria, Research Funding; Trillium: Research Funding; Takeda: Research Funding; Kura Oncology: Research Funding; Aptose: Research Funding; Aprea: Research Funding; Actinium: Research Funding; Boehringer Ingelheim: Research Funding; Abbvie: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Revolution Medicine: Consultancy. Mawad:Adaptive Biotechnologies: Speakers Bureau; Abbvie: Speakers Bureau. Blum:Celyad: Research Funding; Amerisource Bergen: Honoraria; Syndax: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Research Funding; Xencor: Research Funding. Yang:Xencor: Current Employment, Current equity holder in publicly-traded company; Jazz Pharmaceuticals: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Pastore:Novartis NIBR East Hanover New Jersey: Current Employment, Current equity holder in publicly-traded company; Memorial Sloan Kettering Cancer Center: Ended employment in the past 24 months. Johnson:Xencor: Current Employment, Current equity holder in publicly-traded company. Zheng:Xencor: Current Employment, Current equity holder in publicly-traded company; Tocagen: Ended employment in the past 24 months. Yilmaz:Pint Pharma: Honoraria; Pfizer: Research Funding; Daicho Sankyo: Research Funding. Mims:Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Agios: Consultancy; Novartis: Speakers Bureau.

Abstract Background: Blasts and leukemic stem cells of acute myeloid leukemia (AML) as well as several other hematologic malignancies express CD123, potentially providing a target for novel therapies. XmAb14045 (also known as SQZ622) is a potent bispecific antibody targeting both CD123 and CD3 that stimulates targeted T cell-mediated killing of CD123-expressing cells, regardless of T cell antigen specificity. It is a full-length immunoglobulin molecule designed to be dosed intermittently, in contrast to smaller constructs that are referred to as "DART" or "BiTE" bispecific antibodies that require a continuous infusion. Methods: Patients with relapsed or refractory AML, B cell acute lymphoblastic leukemia (B-ALL), blast phase chronic myelogenous leukemia, or blastic plasmacytoid dendritic cell neoplasm were eligible to enroll on this first-in-human, multicenter, open-label phase 1 dose-escalation study (XmAb14045-01) with standard 3+3 design. The primary objective was to estimate the maximum tolerated dose (MTD) or recommended dose and schedule of XmAb14045. Secondary objectives included safety, preliminary antileukemic activity, and pharmacokinetics/pharmacodynamics of XmAb14045. Treatment was administered weekly in 28 day cycles, using a weight-based dose with a single dose level in Part A and, in Part B, an initial priming dose on Day 1 followed by an escalated dose on subsequent weeks. Premedication to prevent cytokine release syndrome (CRS) was instituted as needed and included a steroid, acetaminophen, and diphenhydramine. Patients were premedicated at all XmAb14045 doses ≥0.075 µg/kg. Therapy was continued for as long as tolerated and there was continuing evidence of therapeutic benefit in the opinion of the investigator. Treatment response was assessed by the 2017 European LeukemiaNet (ELN) criteria after Cycle 1 and after each odd-numbered cycle. CRS was graded using the CRS revised grading system (Lee et al., Blood, 2014). Results: At data cut-off, 64 patients have been treated to date, 63 with relapsed/refractory AML and 1 with B-ALL. Patients had a median age of 61 years and were heavily pretreated (median of 3 prior therapies [range 1-8], including 19 [30%] who had undergone prior allogeneic stem cell transplantation). The recommended dose for Part A was 1.3 µg/kg after a single dose-limiting toxicity of Grade 4 CRS at 2.3 µg/kg; no MTD has been identified. CRS or its component symptoms was the most common treatment-emergent adverse event (TEAE). CRS episodes began within approximately 1-4 hours of the start of drug infusion and occurred in 49 of 64 patients (77%). Seven patients (11%) developed Grade ≥3 CRS, the majority of these on the first dose. There were no CRS-related deaths. Excluding CRS-related events, additional TEAEs occurring in >10% of patients included fatigue (31%), febrile neutropenia (30%), peripheral edema (30%), cough (23%), elevated hepatic transaminases (19%; all recovered without sequelae), pneumonia (17%), stomatitis (14%), hyperglycemia (13%), and sepsis (11%). No myelosuppression requiring dose modification or evidence of tumor lysis syndrome was seen. In Part A, single agent antileukemic activity was documented with a best response of CR (2) or CRi (1) in 3/13 AML patients (CR/CRi rate 23%) treated at the two highest dose levels studied to date (1.3 and 2.3 µg/kg weekly); no CR, CRi, or morphologic leukemia-free state (MLFS) responses were seen at lower doses. Antileukemic activity occurred quickly; all responders had achieved at least an MLFS response after 4 doses (1 cycle). Two responders were bridged to stem cell transplantation, and the third was ineligible for medical reasons but remains in remission at 14+ weeks after initiating therapy. Conclusions: XmAb14045 demonstrated evidence of antileukemic activity in heavily pretreated patients with relapsed/refractory AML treated in Part A at the 1.3 and 2.3 µg/kg doses administered once weekly, with a 23% CR/CRi rate. CRS was the most common toxicity but was generally manageable with premedications. The study is ongoing with further optimization of dose, schedule, and premedication regimen for CRS anticipated during accrual to dose escalation cohorts in Part B. ClinicalTrials.gov Identifier: NCT02730312 Disclosures Ravandi: Xencor: Research Funding; Abbvie: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Sunesis: Honoraria; Astellas Pharmaceuticals: Consultancy, Honoraria; Abbvie: Research Funding; Seattle Genetics: Research Funding; Macrogenix: Honoraria, Research Funding; Jazz: Honoraria; Sunesis: Honoraria; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Orsenix: Honoraria; Xencor: Research Funding; Orsenix: Honoraria; Jazz: Honoraria; Bristol-Myers Squibb: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Macrogenix: Honoraria, Research Funding. Foran:Xencor, Inc.: Research Funding; Agios: Research Funding. Stock:Jazz Pharmaceuticals: Consultancy. Mawad:Swedish Cancer Institute: Employment. Blum:Astellas: Consultancy; Pfizer: Consultancy; Boehringer Ingelheim: Research Funding; Forma: Research Funding; Xencor: Research Funding; Tolero: Research Funding. Saville:Xencor, Inc.: Employment, Equity Ownership. Johnson:Xencor, Inc.: Employment, Equity Ownership. Vanasse:Novartis: Employment, Equity Ownership. Ly:Xencor, Inc.: Employment, Equity Ownership. Mims:Novartis: Consultancy; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Abstract Background: Older patients (pts) with AML unfit for intense induction chemotherapy have a poor prognosis with a 5 year survival of <10%. 225Ac-lintuzumab is composed of 225Ac linked to a humanized anti-CD33 monoclonal antibody. Data were previously presented on the initial 13 pts who received 2.0 µCi/kg/dose on Days 1 and 8 (ASH, 2017, Abstract 616). Although that dose resulted in a high response rate of 69%, there were 6 pts with Grade 4 thrombocytopenia lasting >6 weeks and 5 CRi patients did not reach an ANC of ≥ 500/µL. Therefore, the activity level was reduced to 1.5 µCi/kg/dose for further evaluation. Methods: This study enrolled older pts with untreated AML who were considered to be unfit for standard induction chemotherapy. Pts aged 60 to 74 years were required to have significant co-morbidities, while all pts ≥ 75 years were eligible. Other eligibility criteria included ECOG PS 0-2, CD33 expression on > 25% of blasts, and a peripheral blast count <200/µL within 10 days of the first dose to optimize targeting of bone marrow (BM) blasts. Hydroxyurea was used to lower peripheral blast counts. 1.5 µCi/kg of 225Ac-lin were administered IV on Days 1 and 8. G-CSF was given starting 10 days after the 2nd dose and spironolactone was given for up to 1 year to minimize the risk of radiation-induced nephrotoxicity. Pts were evaluated for the CD33 splicing polymorphism SNP rs12459419. Results: 18 pts were included in this prespecified Interim Analysis. An additional 9 pts were treated at this dose and will be included in an updated analysis at the ASH meeting. The median age of the 18 pts was 73.5 years (range 60-87) and median ECOG Performance Status was 1 (0 in 3 pts, 1 in 9 pts, & 6 in 2 pts). 11 pts had prior AHDs (6 MDS, 2 CMML, 2 NHL, 1 myelofibrosis), and 9 had prior treatment for AHDs. Of the pts with known cytogenetic and molecular genetic results, 1 had favorable-risk, 3 had intermediate-risk, and 5 had adverse-risk AML using NCCN guidelines. The median baseline BM blast % was 40.5% (range, 22-66%) with a median CD33 expression of 62% (range, 26-100%) of AML cells. Objective responses were seen in 4 pts (22%): 3 complete remissions with incomplete platelet count recovery (CRp) and 1 complete remission with incomplete hematologic recovery (CRi). Among the responders with known cytogenetics, 1 pt had adverse genetics and 1 had Intermediate-risk genetics.Of the pts with remission, 3 had CT genotype for the CD33 splicing polymorphism SNP rs12459419 (including 2 CRp) and 1 had CC genotype. 3 of the responders are in follow up at Days 59, 169 and 266 without further treatment. Myelosuppression was seen in all pts including Grade 4 thrombocytopenia with marrow aplasia for > 6 weeks after the first dose in 4 pts. 1 pt with prior MDS had pancytopenia for > 4 months. The 3 pts with CRp achieved an ANC ≥ 1000/µL at Days 28, 38, and 40 from the first dose of 225Ac-lin. The pt with CRi did not reach an ANC of 500/µL. Non hematologic Grade ≥3 Treatment-Emergent adverse events (AEs) that were at least possibly related were 4 patients with febrile neutropenia, as well as 1 patient each with fungal pneumonia, acute respiratory failure, pulmonary edema, chest pain, sepsis, gastric hemorrhage, generalized muscle weakness, atrial fibrillation with rapid ventricular response and typhilitis. No pts had an infusion-related reaction requiring dose interruption. Veno-occlusive disease did not occur. The 30-day mortality rate was 16.7% (1 cardiac arrest and 2 with multi organ failure). Conclusions: Preliminary data from this Interim Analysis of 225Ac-lin monotherapy in older AML pts unfit for intensive therapy indicate a lower rate of myelosuppression at 1.5 µCi/kg/dose but also a lower response rate than was seen at 2.0 µCi/kg/dose. Although the study met the prespecified response criteria for continuing enrollment, it will be closed to further accrual in recognition that targeted radiation, like other therapies, will likely have the best outcomes when used in combination with other therapies in pts with active AML. An extensive development program in AML, MDS, and multiple myeloma is planned. One study will utilize 225Ac-lin in combination with salvage chemotherapy and another with venetoclax. 225Ac-lin will be used as a single agent for AML postremission therapy. In addition, 225Ac-lin will be used as targeted conditioning prior to hematopoietic stem cell transplant in pts with MDS with a complex karyotype and as a conditioning agent prior to autologous transplant in MM. Table. Table. Disclosures Atallah: Jazz: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Abbvie: Consultancy; BMS: Consultancy. Orozco:Actinium Pharmaceuticals: Research Funding. Craig:Novartis: Research Funding; Actinium Pharmaceuticals: Research Funding; Celgene: Research Funding. Levy:Takeda (Millennium Pharmaceuticals, Inc.): Consultancy. Finn:Ochsner Clinic Foundation: Employment. Perl:NewLink Genetics: Membership on an entity's Board of Directors or advisory committees; Actinium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Arog: Consultancy; Astellas: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees. Park:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics: Consultancy, Research Funding; Shire: Consultancy; AstraZeneca: Consultancy; Adaptive Biotechnologies: Consultancy; Kite Pharma: Consultancy; Pfizer: Consultancy; Novartis: Consultancy. Roboz:Astex Pharmaceuticals: Consultancy; Bayer: Consultancy; Aphivena Therapeutics: Consultancy; Celltrion: Consultancy; Celgene Corporation: Consultancy; Novartis: Consultancy; Celgene Corporation: Consultancy; Pfizer: Consultancy; Argenx: Consultancy; Roche/Genentech: Consultancy; AbbVie: Consultancy; Cellectis: Research Funding; Aphivena Therapeutics: Consultancy; Roche/Genentech: Consultancy; Sandoz: Consultancy; Bayer: Consultancy; Sandoz: Consultancy; Jazz Pharmaceuticals: Consultancy; Otsuka: Consultancy; Astex Pharmaceuticals: Consultancy; Daiichi Sankyo: Consultancy; Orsenix: Consultancy; Janssen Pharmaceuticals: Consultancy; AbbVie: Consultancy; Jazz Pharmaceuticals: Consultancy; Argenx: Consultancy; Janssen Pharmaceuticals: Consultancy; Eisai: Consultancy; Otsuka: Consultancy; Pfizer: Consultancy; Eisai: Consultancy; Orsenix: Consultancy; Cellectis: Research Funding; Daiichi Sankyo: Consultancy; Novartis: Consultancy; Celltrion: Consultancy. Tse:Brown Cancer Center, University of Louisville School of Medicine: Employment; Jazz: Consultancy; Amgen: Consultancy; Amgen: Honoraria; Amgen: Honoraria. Mawad:Swedish Cancer Institute: Employment. Rizzieri:Novartis: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Teva: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Arog: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Berger:Actinium Pharmaceuticals: Employment, Equity Ownership. Jurcic:Astellas: Research Funding; Daiichi-Sankyo: Research Funding; Incyte: Consultancy; Celgene: Research Funding; AbbVie: Consultancy, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Research Funding; Syros Pharmaceuticals: Research Funding; Actinium Pharmaceuticals, Inc: Research Funding; Genetech: Research Funding; Kura Oncology: Research Funding.