Array Biopharma Research Articles

The Impact of the Administration Schedule and Mutational Profile on Outcomes of Patients with Relapsed and Refractory Acute Myeloid Leukemia Treated with Hypomethylating Agents: A Large, International, Multi-Center Analysis

The Impact of the Administration Schedule and Mutational Profile on Outcomes of Patients with Relapsed and Refractory Acute Myeloid Leukemia Treated with Hypomethylating Agents: A Large, International, Multi-Center Analysis

Randomized Phase II Study of Axitinib Versus Observation in Patients with Recurred or Metastatic Adenoid Cystic Carcinoma

BACKGROUND: Adenoid cystic carcinoma (ACC) does not respond to cytotoxic chemotherapy. While several anti-angiogenic agents have been evaluated in single-arm phase II trials, the role of chemotherapy is still controversial because ACC is usually stable without chemotherapy and lack of randomized trials. Here, we conducted the first randomized trial to evaluate the efficacy of axitinib as compared to observation in ACC. METHODS: In this multicenter, prospective phase II trial, we enrolled recurred, metastatic ACC patients who had progressed within the past 9 months. Patients were randomly assigned to either axitinib (5 mg twice daily) or observation at a 1:1 ratio. Crossover from observation to axitinib was permitted for patients who showed progression. The primary endpoint was a 6-month progression-free survival (PFS) rate. The secondary endpoints included objective response rate (ORR), overall survival (OS), PFS, duration of response, and adverse events. FINDINGS: Sixty patients were randomly allocated to axitinib or observation, with response evaluation conducted in 54 patients. With a median follow-up of 25.4 months, the 6-month PFS rate was 73.0% with axitinib and 23.0% with observation. Median PFS was significantly different ( P < 0.001) between the two arms. The ORR of axitinib was 0.0%. The disease control rate was 100.0% with axitinib and 51.9% with observation. After crossover, ORR of axitinib in the observation arm was 11.5%. Median OS was not reached with axitinib versus 27.2 months with observation ( P = 0.226). The most frequently reported adverse events for axitinib were oral mucositis and fatigue. INTERPRETATION: In this first randomized trial in patients with recurred or metastatic ACC, axitinib significantly increased the 6-month PFS rate as compared to observation. TRIAL REGISTRATION: (ClinicalTrials.gov number, NCT02859012) FUNDING STATEMENT: Adenoid Cystic Carcinoma Research Foundation, and National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1720150). DECLARATION OF INTERESTS: BK received research funding from MSD, AstraZeneca, and Ono Pharmaceutical and served as an advisor for AstraZeneca, MSD, Handok, CBS Bio and Genexine outside of the current work. M-J A received research funding from AstraZeneca and received honoraria from AstraZeneca, Lilly, Novartis, MSD, TAKEDA, Alpha pharmaceutical, Roche, Ono Pharmaceutical and served as an advisor or consultancy for AstraZeneca, Lilly, Novartis, MSD, TAKEDA, Alpha Pharmaceutical, Roche and Ono pharmaceutical. K-W L received honoraria from BMS, Lilly, Genexine and received research funding from Macrogenics, MSD, Ono Pharmaceutical, Green Cross Corp. ASLAN Pharmaceuticals and AstraZeneca/MedImmune, Five Prime Therapeutics, LSK BioPharma, Merck, Array BioPharma, Pharmacyclics, Pfizer, ALX Oncology, Zymeworks, BeiGene, Daiichi Sankyo, Taiho Pharmaceutical, and served as an advisor or consultancy for Bayer. S-BK received research funding from Novartis, Sanofi- Genzyme, Dongkook Pharmaceutical Co., Ltd and served as an advisor or consultancy for Novartis, Astrazeneca, Lilly, Enzychem, Dae Hwa Pharmaceutical Co.,Ltd, ISU Abxis and Daiichi-Sankyo.YY served as an advisor or consultancy for Lilly.MKK received honoraria from Janssen Korea. All other authors declare no competing interests. ETHICS APPROVAL STATEMENT: The study protocol was approved by the Institutional Review Board of each participating institution.

Transcriptomics in Tumor and Normal Tissues and Precision Oncology Algorithms Identify Early-Stage NSCLC Patients with High Risk of Post-Surgery Recurrence Who May Benefit from Adjuvant Therapies

Background: The prognosis of patients with non-small cell lung cancer (NSCLC) is traditionally determined by anatomic staging using the Tumor, Node, Metastasis (TNM) staging system. TNM staging neglects the biological features of the tumor that may be important in determining patient outcome and guiding therapeutic interventions. Identifying NSCLC patients at increased risk of recurrence after curative-intent surgery remains an important unmet need as adjuvant therapies are available that may reduce the risk of recurrence and improve patient survival. Methods: Digital Display Precision Predictor (DDPP), based on differential RNA expression in tumor versus normal tissue, was used to interrogate gene sets to determine their association with disease-free survival (DFS) in patients with non-small cell lung cancer (NSCLC) who underwent curative-intent surgery. Findings: Low versus high DDPP score was significantly associated with shorter DFS (highest recurrence risk): HR=1.88, 95% CI [1.2-2.9] (p=0.006) in all patients (n=120) and in patients with TNM stages 1-2 (p= 0.00051) (n=83). For patients with stages 1-2 and low DDPP (n=29), adjuvant chemotherapy was associated with improved DFS (p= 0.0041). High co-overexpression of CTLA-4, PD-L1 and ICOS in normal lung (28 of 120 patients), hypothesized to reflect the host immune status, was also significantly associated with decreased DFS (p= 0.0013) suggesting an immune tolerance to tumor neoantigens in some patients. Patients with DDPP low and immunotolerant normal tissue had the shortest DFS (p=2.12E-11). Interpretation: We identified stage 1-2 NSCLC patients with high risk of recurrence who benefitted from adjuvant chemotherapy. Furthermore, identified a subset of NSCLC patients who may have poor post-surgery outcome related to an immunotolerant normal tissue profile that might be amenable to modulation by specific checkpoint blockade immunotherapies. Funding: European Union Frame Pprogram 6-funded project (Chemores FP6 Health, Grant 37 665). Declaration of Interest: Dr. Vladimir Lazar, Catherine Bresson, are full time employees of Worldwide Innovative Network (WIN) Association - WIN Consortium. Worldwide Innovative Network (WIN) Association - WIN Consortium is the owner of the patent family entitled Digital Display. The inventors are Dr. Vladimir Lazar, and Shai Magidi. Dr. Jean-Francois Martini, is a full-time employee and stockholder of Pfizer Inc. Dr. Susan Galbraith is a full-time employee and stockholder of AstraZeneca. Dr. Benjamin Solomon received honorarium for Advisory Board from AstraZeneca and Bayer. Shai Magidi receives consultancy from Worldwide Innovative Network (WIN) Association. Dr. Amir Onn receives consulting fees from Roche Israel, MSD Israel, Boehringer Ingelheim 552 and AstraZeneca. Dr. Enriqueta Felip receives advisory board and/or speaker’s bureau fee from Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-LaRoche, Glaxi Smith Kline, Janssen, Medical Trends, Medscape, Merck Sharp & Dohme, Merck Serono, Peptomyc, Peervoice, Pfizer, Puma, Regeneron, Sanofi, Springer, Syneos Health, Takeda, Touch Medical; on the board of Grifols, Independent member. Receives research funding from Fundacion Merck Salud, Grant for Oncology Innovation (GOI) EMD Serono. Dr. Josep Tabernero declares scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, F. Hoffmann-La Roche Ltd, Sanofi, SeaGen, Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. Dr. Gerald Batist collaborates in formal clinical trial contracts, IITs and in joint grants funded by Canadian and Quebec governments with Roche, Merck, Novartis, Astra-Zeneca, Bayer, Esperas, Aurka, Caprion, MRM. Pr. Angel Porgador declares scientific consultancy role for PiNK Biopharma. Dr. Razelle Kurzrock has received research funding from Genentech, Merck Serono, Pfizer, Boehringer Ingelheim, TopAlliance, Takeda, Incyte, Debiopharm, Medimmune, Sequenom, Foundation Medicine, Konica Minolta, Grifols, Omniseq, and Guardant, as well as consultant and/or speaker fees and/or advisory board for X-Biotech, Neomed, Pfizer, Actuate Therapeutics, Roche, Turning Point Therapeutics, TD2/Volastra, Bicara Therapeutics, Inc., and Biological Dynamics, has an equity interest in IDbyDNA and CureMatch Inc, serves on the Board of CureMatch and CureMetrix, and is a co-founder of CureMatch. Dr. Richard L. Schilsky’s institution (ASCO) receives research grants in support of a clinical trial that he directs from the following companies: AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Genentech, Lilly, Merck, Pfizer. Dr. Schilsky reports being a consultant to Cellworks, Clarify Precision Medicine, Bryologx, EQRx and Scandion Oncology. The remaining authors declare no competing interests. Ethical Approval: The bio-banking study was approved by the IMM’s Ethics Committee.

Updated Phase 1 Results of Teclistamab, a B-Cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Relapsed and/or Refractory Multiple Myeloma (RRMM)

Updated Phase 1 Results of Teclistamab, a B-Cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Relapsed and/or Refractory Multiple Myeloma (RRMM)

Updated Analysis of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (NDMM): The Phase 3 Maia Study

Updated Analysis of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (NDMM): The Phase 3 Maia Study

Phase 1b Study of BET Inhibitor PLX2853 in Patients with Relapsed or Refractory Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Phase 1b Study of BET Inhibitor PLX2853 in Patients with Relapsed or Refractory Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Evaluation of Minimal Residual Disease (MRD) Negativity in Patients with Relapsed or Refractory Multiple Myeloma Treated in the Candor Study

Evaluation of Minimal Residual Disease (MRD) Negativity in Patients with Relapsed or Refractory Multiple Myeloma Treated in the Candor Study

Preliminary Results of Balli-01: A Phase I Study of UCART22 (allogeneic engineered T-cells expressing anti-CD22 Chimeric Antigen Receptor) in Adult Patients with Relapsed or Refractory (R/R) CD22+ B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Preliminary Results of Balli-01: A Phase I Study of UCART22 (allogeneic engineered T-cells expressing anti-CD22 Chimeric Antigen Receptor) in Adult Patients with Relapsed or Refractory (R/R) CD22+ B-Cell Acute Lymphoblastic Leukemia (B-ALL)

CC-486 Improves Overall Survival (OS) and Relapse-Free Survival (RFS) for Patients with Acute Myeloid Leukemia (AML) in First Remission after Intensive Chemotherapy (IC), Regardless of Amount of Consolidation Received: Results from the Phase III QUAZAR AML-001 Maintenance Trial

CC-486 Improves Overall Survival (OS) and Relapse-Free Survival (RFS) for Patients with Acute Myeloid Leukemia (AML) in First Remission after Intensive Chemotherapy (IC), Regardless of Amount of Consolidation Received: Results from the Phase III QUAZAR AML-001 Maintenance Trial

28-Day Metronomic Therapy for Relapsed Refractory Multiple Myeloma

Background: The advent of novel therapies has led to tremendous progress in the treatment of multiple myeloma (MM). However, management of patients with high-risk disease who have failed approved agents and have rapidly progressive disease with cytopenias continues to be challenging. While palliative care is an option, many patients hope to qualify for a clinical trial option. Here we report results of a 28-day metronomic therapy (METRO-28) consisting of continuous administration of very low doses of classical chemotherapeutic agents. Sixteen-day cycles of metronomic therapy were previously shown to have a favorable response with acceptable toxicity profiles in MM patients (Papanikolaou et al. Haematologica 2013). Aim: To investigate the efficacy and toxicity in patients with high-risk relapsed refractory MM (RRMM) ineligible for clinical trial options receiving 1 cycle of METRO-28. Method: We retrospectively analyzed the clinical outcomes of 106 RRMM, treated with 1 cycle of 28-day metronomic chemotherapy at the Tisch Cancer Institute - The Mount Sinai Hospital. METRO-28 consists of 6 agents: dexamethasone 8 mg on days 1 through 4, 7 through 10, 13 through 16, 19 through 22 and 25 through 28; bortezomib 1 mg/m2 on days 1, 4, 7, 10, 13, 16, 19, 22, 25, 28; cisplatin 1 mg/m2 daily; doxorubicin 1 mg/m2 daily; thalidomide 100 mg daily; and vincristine flat dose 0.06 mg daily. METRO-28 was administered through a central line in either the inpatient or outpatient setting. Result: Our cohort of 106 RRMM patients has a median age of 65 years (range: 35-85) and at a median of 59 months from time of diagnosis; 42% were females. They had a median of 7 prior lines of therapy (range: 1 - 25); with 73% triple- and 58% penta-refractory cases. Prior autologous transplantation was utilized in 69% of patients including tandem transplants in 30%. Moreover, 78% of patients carried high-risk cytogenetic features, including 1q21 duplication/amplification (89%), 17p deletion (49%), t(4;14) (17%), t(14;16) (17%) or t(14;20) (3%). At the time of METRO-28 initiation, patients were cytopenic with grade 3 and 4 anemia (21%), neutropenia (8%) and thrombocytopenia (23%). Profound cytopenias in some patients led to early discontinuation of treatment; forty-three patients (41%) received the full 28-day course of METRO-28, while 11%, 17%, 20% and 11% were treated for &amp;lt;1 week, &amp;lt;2 weeks, &amp;lt;3 weeks or &amp;lt;4 weeks, respectively. Grade 3-4 cytopenia increased: anemia 66%, leucopenia 61%, neutropenia 55% and thrombocytopenia 76%. On an intent to treat basis (106 patients), the deepest response included 2% stringent complete response (sCR), 7% near complete response (nCR), 7% very good partial response (VGPR), 28% partial response (PR), 11% minimal response (MR) and 12% stable disease (SD). Only 43 patients (41%) completed all 4 weeks of METRO-28 and had a 72% overall response rate (ORR) and 88% clinical benefit rate (CBR). Seventy-four percent of these patients were able to move on to new therapies, including novel agents and clinical trials. Their overall survival (OS) was 11.8 months (range: 6.1-NE) as opposed to an OS of 4.2 months (range: 3.4-7.2) for patients with &amp;lt;4 weeks of METRO-28. Sixty-three patients had their treatment interrupted: 34 due to disease progression or absence of response, 18 due to bacterial or viral infections and 11 due to hematologic toxicity. Conclusion: Giving 1 cycle of METRO-28 is better tolerated in patients with good hematologic reserve and offers an opportunity for a clinical benefit and a bridge to a subsequent treatment option for these advanced refractory myeloma patients. Disclosures Richter: Takeda: Consultancy; Janssen: Speakers Bureau; Sanofi: Consultancy; AstraZeneca: Consultancy; X4 Pharmaceuticals: Consultancy; Adaptive Biotechnologies: Consultancy, Speakers Bureau; Oncopeptides: Consultancy; Secura Bio: Consultancy; Antengene: Consultancy; Karyopharm: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy, Speakers Bureau. Parekh:Foundation Medicine: Consultancy; Celgene: Research Funding; Karyopharm: Research Funding. Chari:Adaptive Biotechnology: Honoraria; The Binding Site: Honoraria; Array BioPharma: Honoraria; Novartis: Honoraria; Secura Bio: Consultancy; Glaxo Smith Kline: Consultancy; Antengene: Consultancy; Takeda: Consultancy, Research Funding; Oncopeptides: Consultancy; Seattle Genetics: Consultancy, Research Funding; Sanofi Genzyme: Consultancy; Karyopharm: Consultancy; Pharmacyclics: Research Funding; Bristol Myers Squibb: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Jagannath:Legend Biotech: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Madduri:Janssen: Consultancy; BMS: Consultancy; Takeda: Consultancy; Legend: Consultancy; Sanofi: Consultancy; GSK: Consultancy; Kinevant: Consultancy; Foundation Medicine: Consultancy.

CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel, a B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy, in Relapsed/Refractory Multiple Myeloma

CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel, a B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy, in Relapsed/Refractory Multiple Myeloma

A Polish Acute Leukemia Group Prospective Multicenter Clinical Trial to Compare the Efficacy of Two Standard Induction Therapies (DA-90 vs DAC) and Two Standard Salvage Regimens (FLAG-IDA vs CLAG-M) in Acute Myeloid Leukemia (AML) Patients ≤ 60 Years Old (PALG-AML1/2016)

Background: AML is the most common acute leukemia in adults. While most adults &amp;lt; 60 years achieve complete remission (CR) with intensive induction chemotherapy, approximately one third have primary refractory disease and, overall, the majority of AML patients still relapse despite having attained initial remission (Dohner et al, Blood 2017). The combination of an anthracycline and cytarabine has been the mainstay of intensive AML induction for more than 50 years. Combined with cytarabine (AraC), high-dose daunorubicin (90 mg/m2) in induction (DA-90) resulted in a higher rate of CR (70.6% vs. 57.3%, P&amp;lt;0.001) and improved overall survival (OS) (median 23.7 vs. 15.7 months; P = 0.003), without increased serious adverse events compared with DA-45 (Fernandez et al, NEJM, 2009). In two PALG randomized trials, the combination of cladribine with DA (DAC regimen) also resulted in significantly increased CR after a single induction course, compared with the standard two-drug induction (DA-60) (Holowiecki et al, Leukemia, 2004 and JCO 2012). Both regimens have a recommendation from the National Cancer Comprehensive Network (NCCN) for routine use. For patients with primary refractory disease, the commonly used FLAG-IDA (fludarabine, cytarabine, idarubicin, GCSF) regimen results in a CR rate of 52% (Pastore et al, Ann Hem, 2003). Two previous PALG studies confirmed that another standard regimen, CLAG-M (a combination of cladribine, Ara-C, G-CSF and mitoxantrone) is also effective with tolerable toxicity in refractory/relapsed AML patients (Robak et al Leuk Lymph, 2000; Wrzesień-Kuś et al, Eur J Haematol 2003; Wrzesień-Kuś et al, Ann Hematol, 2005; Wierzbowska et al, Eur J Haematol ,2008; Jaglal et al, Leuk Res, 2014). PALG-AML1/2016 aims to compare the safety and efficacy of two commonly used induction and salvage regimens in AML. This trial is also the first international randomized trial in AML induction to prospectively evaluate the impact of measurable residual disease (MRD) on overall survival, using multi-modality testing (flow-cytometry, next-generation sequencing, and PCR) of serial samples. The study is conducted in accordance with the principles of the "Declaration of Helsinki". Study Design and Methods: PALG-AML1/2016 is a multicenter, randomized, Phase III study which will include 582 patients with newly-diagnosed AML treated at multiple centers across Poland and at Weill Cornell Medicine and The New York Presbyterian Hospital in New York City. This will allow a 10% difference in CR rate between the DAC and DA-90 induction regimens to be confirmed with a power of 80% and level of significance 0.05. Eligible patients must be 18 to 60 years of age with untreated AML, Eastern Cooperative Oncology Group performance status 0-2 and HCT-CI Index of comorbidities, ≤ 3. As midostaurin treatment has become approved and available the study was amended with an exclusion of FLT3-mutated patients. The trial schema is shown in Figure 1. The trial was initiated in July 2017 and 279 patients have been enrolled to date and accrual is ongoing. Preliminary safety and efficacy data were reviewed by the data safety monitoring committee after 194 patients and the recommendation was to proceed without changes. Serial samples for MRD are being collected from all patients at multiple time points and analysis is ongoing. ClinicalTrials.gov Identifier: NCT03257241 Figure 1 Disclosures Wierzbowska: Janssen: Honoraria; Celgen/BMS: Honoraria; Novartis: Honoraria; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Research Funding. Pluta:Angelini: Research Funding; Celgene/BMS: Honoraria. Libura:Novartis: Honoraria. Wrobel:Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau. Zaucha:Abbvie: Honoraria; Sandoz: Consultancy, Honoraria; Cellgene: Other: travel, accomodations, expenses; Novartis: Consultancy; BMS: Consultancy; Takeda: Consultancy, Honoraria, Other: travel, accomodations, expenses; Roche: Consultancy, Honoraria, Other: travel, accomodations, expenses. Robak:AstraZeneca: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; GSK: Research Funding; Bristol Meyers Squibb: Research Funding; Novartis: Honoraria, Research Funding; Morphosys: Research Funding; UCB: Honoraria, Research Funding; Roche: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; UTX-TGR: Research Funding; BioGene: Honoraria, Research Funding; Acerta: Research Funding; Momenta: Consultancy; Pfizer: Research Funding; Sandoz: Consultancy, Honoraria; Octapharma: Honoraria; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; Medical University of Lodz: Current Employment; Takeda: Consultancy. Lee:BMS: Consultancy; Helsinn: Other: Member -DSMB; AstraZeneca: Consultancy; Jazz: Consultancy; Roche Molecular Systems: Consultancy. Ritchie:Novartis: Honoraria; Incyte: Speakers Bureau; Sierra Oncology: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria, Research Funding; Jazz pharmaceuticals: Honoraria, Research Funding. Guzman:Cellectis: Research Funding; SeqRx: Honoraria. Roboz:Agios: Consultancy; Amphivena: Consultancy; Astex: Consultancy; Pfizer: Consultancy; Abbvie: Consultancy; Array BioPharma: Consultancy; Bayer: Consultancy; Celltrion: Consultancy; Eisai: Consultancy; Jazz: Consultancy; Roche/Genentech: Consultancy; Sandoz: Consultancy; Actinium: Consultancy; Argenx: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; AstraZeneca: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Takeda: Consultancy; Trovagene: Consultancy; Cellectis: Research Funding; Jasper Therapeutics: Consultancy; Epizyme: Consultancy; Helsinn: Consultancy; MEI Pharma: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Novartis: Consultancy. OffLabel Disclosure: cladribine - in induction regimen in AML

Response-Adaptive Phase II Study of Daratumumab Combined with Carfilzomib, Lenalidomide and Dexamethasone in Newly Diagnosed Multiple Myeloma

Response-Adaptive Phase II Study of Daratumumab Combined with Carfilzomib, Lenalidomide and Dexamethasone in Newly Diagnosed Multiple Myeloma

Clinical Efficacy and Safety of Oral Decitabine/Cedazuridine in 133 Patients with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

Clinical Efficacy and Safety of Oral Decitabine/Cedazuridine in 133 Patients with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

Cytokine Release Syndrome in Patients with Relapsed/Refractory Multiple Myeloma Treated with Ciltacabtagene Autoleucel in the Phase 1b/2 CARTITUDE-1 Study

Cytokine Release Syndrome in Patients with Relapsed/Refractory Multiple Myeloma Treated with Ciltacabtagene Autoleucel in the Phase 1b/2 CARTITUDE-1 Study

Health-Related Quality of Life in the Cartitude-1 Study of Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma

Health-Related Quality of Life in the Cartitude-1 Study of Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma

Sustained Minimal Residual Disease (MRD) Negativity and Clinical Efficacy in Transplant-Ineligible (TIE) Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Treated with Daratumumab-Based Regimens: Analysis of Maia and Alcyone

Sustained Minimal Residual Disease (MRD) Negativity and Clinical Efficacy in Transplant-Ineligible (TIE) Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Treated with Daratumumab-Based Regimens: Analysis of Maia and Alcyone

KarMMa-4: Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T-Cell Therapy, in High-Risk Newly Diagnosed Multiple Myeloma

BACKGROUND: Despite the introduction of novel agents, patients with high-risk (Revised International Staging System [R-ISS] stage III) newly diagnosed multiple myeloma (NDMM) have a poor prognosis (median progression-free survival [PFS], 29 months), highlighting the need for novel disease-targeting approaches (Palumbo A, et al. J Clin Oncol. 2015;33:2863-2869). The BCMA-directed CAR T cell therapy ide-cel demonstrated deep, durable responses in heavily pretreated patients with relapsed and refractory MM (RRMM; Raje N, et al. N Engl J Med. 2019;380:1726-1737; Munshi NC, et al. J Clin Oncol. 2020;38[suppl] [abstract 8503]), including those with high-risk (R-ISS stage III) RRMM. Earlier use in this population-where there is potentially more bone marrow reserve, more healthy peripheral blood mononuclear cells, a less compromised immune status, and less extensive disease to debulk before cell therapy-may result in improved outcomes and offer an opportunity to replace transplant with CAR T cell therapy. KarMMa-4 is a multicenter, open-label, phase 1, single-arm study of ide-cel in patients with high-risk NDMM (R-ISS stage III disease per International Myeloma Working Group criteria). STUDY DESIGN: KarMMa-4 is enrolling patients with NDMM who have high-risk disease, defined as R-ISS stage III (ISS stage III [serum b2 microglobulin ≥ 5.5 mg/L] and cytogenetic abnormalities t(4;14), del(17p), and/or t(14;16) by interphase fluorescence in situ hybridization; or ISS stage III and serum lactate dehydrogenase &amp;gt; upper limit of normal). Patients must have received ≤ 3 cycles of the induction regimens listed below, be aged ≥ 18 years, and have Eastern Cooperative Oncology Group performance status 0-1. Patients with nonsecretory myeloma or central nervous system involvement are excluded. Patients can enroll between cycle 1 and cycle 3 of induction. Permitted induction regimens for cycle 1 are carfilzomib + lenalidomide + dexamethasone ± daratumumab (KRd ± DARA), lenalidomide + bortezomib + dexamethasone ± daratumumab (RVd ± DARA), or cyclophosphamide + bortezomib + dexamethasone (CyBorD). Induction regimens for cycles 2-4 are limited to KRd or RVd, with dexamethasone omitted during cycle 3. All patients will undergo leukapheresis for T cell collection after cycle 3, and ide-cel will be manufactured during cycle 4 of induction. Stem cell collection for future use may be conducted after cycle 3 (following leukapheresis) or cycle 4 (before lymphodepletion). Ide-cel is infused after 2 days of rest following lymphodepletion with 3 days of fludarabine 30 mg/m2 + cyclophosphamide 300 mg/m2. Lenalidomide-based maintenance may be provided upon bone marrow recovery or 90 days after ide-cel infusion, whichever is later. The primary endpoints are dose-limiting toxicity and safety. Secondary endpoints include complete response rate and overall response rate, duration of response, time to complete response, time to start of maintenance, feasibility of initiating maintenance, PFS, overall survival, and pharmacokinetics. Exploratory endpoints include safety of lenalidomide maintenance therapy, minimal residual disease, immunogenicity and biomarkers. The starting ide-cel target dose is 450 × 106 CAR+ T cells, with dose escalation/de-escalation (150, 300, and 800 × 106 CAR+ T cells). After identification of the optimal target dose, 12 patients will be enrolled in the dose-expansion phase. KarMMa-4 is registered at ClinicalTrials.gov: NCT04196491. Disclosures Usmani: Celgene: Other; 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; Merck: Consultancy, Research Funding; Incyte: Research Funding; Pharmacyclics: Research Funding; Array Biopharma: Research Funding; GSK: Consultancy, Research Funding; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding. Berdeja:Servier: Consultancy; Poseida: Research Funding; Lilly: Research Funding; Legend: Consultancy; Kite Pharma: Consultancy; Kesios: Research Funding; Karyopharm: Consultancy; Prothena: Consultancy; Acetylon: Research Funding; Amgen: Consultancy, Research Funding; Abbvie: Research Funding; Vivolux: Research Funding; Novartis: Research Funding; Bluebird: Research Funding; Bioclinica: Consultancy; BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Cellularity: Research Funding; Constellation: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; CURIS: Research Funding; EMD Sorono: Research Funding; Genentech, Inc.: Research Funding; Janssen: Consultancy, Research Funding; Glenmark: Research Funding; Teva: Research Funding; Takeda: Consultancy, Research Funding. Truppel-Hartmann:bluebird bio, Inc: Current Employment, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); F. Hoffmann La Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Casadebaig:Bristol-Myers Squibb Company: Current Employment. Wortman-Vayn:Bristol-Myers Squibb Company: Current Employment. Shelat:Bristol-Myers Squibb Company: Current Employment. Novick:Bristol-Myers Squibb Company: Current Employment. Shah:GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy; BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding.

Ameli-01: Phase I, Open Label Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Expansion, Persistence and Clinical Activity of UCART123 (allogeneic engineered T-cells expressing anti-CD123 chimeric antigen receptor), Administered in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Ameli-01: Phase I, Open Label Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Expansion, Persistence and Clinical Activity of UCART123 (allogeneic engineered T-cells expressing anti-CD123 chimeric antigen receptor), Administered in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Patient Expectations and Perceptions of Treatment in CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma

Patient Expectations and Perceptions of Treatment in CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma