DOCSLIB.ORG

Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia HEMATOLOGIC MALIGNANCIES—LYMPHOMA AND CHRONIC LYMPHOCYTIC LEUKEMIA 7500 Oral Abstract Session First results of a head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia. John C. Byrd, Peter Hillmen, Paolo Ghia, Arnon P. Kater, Asher Alban Akmal Chanan-Khan, Richard R. Furman, Susan M. O’Brien, Mustafa Nuri Yenerel, A�rpa�d Ille�s, Neil E. Kay, Jose Antonio Garcia Marco, Anthony R. Mato, John Francis Seymour, Stephane Lepre^tre, Stephan Stilgenbauer, Tadeusz Robak, Priti Patel, Kara Higgins, Sophia Sohoni, Wojciech Jurczak; The Ohio State University Wexner Medical Center, Columbus, OH; St. James’s University Hospital, Leeds, United Kingdom; Universita� Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy; Amsterdam University Medical Center, Amsterdam, on behalf of Hovon, Amsterdam, Netherlands; Mayo Clinic, Jacksonville, FL; Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA; Liv Hospital Ulus, Besiktas, Turkey; University of Debrecen, Debre- cen, Hungary; Mayo Clinic, Rochester, MN; Hospital Universitario Puerta de Hierro-Majadahonda, Ma- drid, Spain; University of Pennsylvania, Philadelphia, PA; Peter MacCallum Cancer Centre & Royal Melbourne Hospital, Melbourne, Australia; Centre Henri Becquerel and Normandie University UNI- ROUEN, Rouen, France; University of Ulm, Ulm, Germany; Medican University of Lodz, Lodz, Poland; AstraZeneca, South San Francisco, CA; Maria Sklodowska-Curie National Research Institute of Oncolo- gy, Krakow, Poland Background: Increased selectivity of the Bruton tyrosine kinase inhibitor (BTKi) acalabrutinib (Aca) vs ibrutinib (Ib) may improve tolerability. We conducted an open-label, randomized, noninferiority, phase 3 trial to compare Aca vs Ib in patients (pts) with chronic lymphocytic leukemia (CLL). Methods: Previ- ously treated CLL pts with del(17p) or del(11q) by central lab were randomized to receive oral Aca 100 mg BID or Ib 420 mg QD (stratified by del(17p) status, ECOG PS [2 vs #1], and number of prior thera- pies [1–3 vs $4]) until progression or unacceptable toxicity. Primary endpoint was progression-free sur- vival (PFS) as assessed by IRC; secondary endpoints of all grade atrial fibrillation (AF), grade $3 infection, Richter transformation, and overall survival (OS) were assessed in hierarchical order. Results: 533 pts (Aca, n=268; Ib, n=265) were randomized (median age 66 y; median 2 prior therapies; del(17p) 45.2%; del(11q) 64.2%). At a median follow-up of 40.9 mo (range 0.0–59.1), Aca was non- inferior to Ib with a median PFS of 38.4 mo in both arms (HR 1.00; 95% CI 0.79–1.27). Aca was statis- tically superior to Ib in all-grade AF incidence (9.4% vs 16.0%; P=0.023). Among the other secondary endpoints, incidences of grade $3 infection (Aca: 30.8%, Ib: 30.0%) and Richter transformation (Aca: 3.8%, Ib: 4.9%) were comparable between arms. Median OS was not reached in either arm (HR 0.82 [95% CI 0.59–1.15]), with 63 (23.5%) deaths in the Aca arm and 73 (27.5%) in the Ib arm. Among any-grade AEs in $20% of pts in either arm, Aca was associated with a lower incidence of hypertension (9.4%, 23.2%), arthralgia (15.8%, 22.8%), and diarrhea (34.6%, 46.0%) but a higher incidence of headache (34.6%, 20.2%) and cough (28.9%, 21.3%). AEs led to treatment discontinuation in 14.7% of Aca- vs 21.3% of Ib-treated pts. Among any-grade events of clinical interest, cardiac, hyper- tension, and bleeding events were less frequent with Aca (Table). Conclusions: In this first head-to-head trial of BTKis in CLL, Aca demonstrated non-inferior PFS with less cardiotoxicity and fewer discontinua- tions due to AEs vs Ib. Clinical trial information: NCT02477696. Research Sponsor: Acerta Pharma, a member of the AstraZeneca Group. Selected events of clinical interest. Acalabrutinib (n = 266) Ibrutinib (n = 263) Events, n (%) Any grade Grade $3 Any grade Grade $3 Cardiac events 64 (24.1) 23 (8.6) 79 (30.0) 25 (9.5) Atrial fibrillationa 25 (9.4) 13 (4.9) 42 (16.0) 10 (3.8) Ventricular tachyarrhythmias 0 0 1 (0.4) 1 (0.4) Hypertensionb 25 (9.4) 11 (4.1) 61 (23.2) 24 (9.1) Bleeding events 101 (38.0) 10 (3.8) 135 (51.3) 12 (4.6) Major bleeding eventsc 12 (4.5) 10 (3.8) 14 (5.3) 12 (4.6) Infections 208 (78.2) 82 (30.8) 214 (81.4) 79 (30.0) Second primary malignancies excluding non-melanoma skin cancers 24 (9.0) 16 (6.0) 20 (7.6) 14 (5.3) aIncludes atrial fibrillation and atrial flutter bIncludes hypertension, blood pressure increased, and blood pressure systolic increased cAny hemorrhagic event that was serious, grade $3, or a CNS hemorrhage (any grade). © 2021 by American Society of Clinical Oncology. Visit abstracts.asco.org and search by abstract for disclosure information. HEMATOLOGIC MALIGNANCIES—LYMPHOMA AND CHRONIC LYMPHOCYTIC LEUKEMIA 7501 Oral Abstract Session Fixed-duration (FD) first-line treatment (tx) with ibrutinib (I) plus venetoclax (V) for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary analysis of the FD cohort of the phase 2 captivate study. Paolo Ghia, John N. Allan, Tanya Siddiqi, Thomas J. Kipps, Ryan Jacobs, Stephen Opat, Paul M. Barr, Alessandra Tedeschi, Livio Trentin, Rajat Bannerji, Sharon Jackson, Byrone Kuss, Carol Moreno, Edith Szafer-Glusman, Kristin Russell, Cathy Zhou, Joi Suzuki Ninomoto, James P. Dean, William G. Wierda, Constantine Si Lun Tam; Universita� Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy; Weill Cornell Medicine, New York, NY; City of Hope National Medical Center, Duarte, CA; Univer- sity of California San Diego Moores Cancer Center, La Jolla, CA; Levine Cancer Institute, Charlotte, NC; Monash University, Clayton, Australia; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY; ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Hematology and Clinical Immunology Unit, Department of Medicine, University of Padova, Padua, Italy; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Middlemore Hospital, Auckland, New Zealand; Flinders University and Medical Centre, Bedford Park, SA, Australia; Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA; Pharmacyclics Inc, Sunnyvale, CA; De- partment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; Peter Mac- Callum Cancer Centre & St. Vincent’s Hospital and the University of Melbourne, Melbourne, Australia Background: CAPTIVATE (PCYC-1142) is a multicenter phase 2 study of first-line I+V in CLL. We previ- ously reported results from the Minimal Residual Disease (MRD) cohort wherein undetectable MRD (uMRD) was achieved in over two-thirds of patients (pts) with 12 cycles of I+V, and 30-mo PFS rates were $95% irrespective of subsequent randomized treatment (Wierda, ASH 2020). We now present re- sults from the FD cohort, evaluating fixed-duration tx with I+V. Methods: Pts aged #70 y with previously untreated CLL/SLL received 3 cycles of I then 12 cycles of I+V (I 420 mg/d orally; V ramp-up to 400 mg/d orally). Primary endpoint was CR rate, including CR with incomplete recovery (CRi); secondary endpoints were ORR, duration of response, uMRD rate (<10-4 by 8-color flow cytometry), PFS, OS, tu- mor lysis syndrome (TLS) risk reduction, and adverse events (AEs). Results: 159 pts were enrolled (me- dian age 60 y). High-risk features included del(17p)/TP53 mutation, 17%; del(11q), 18%; complex karyotype, 19%; and unmutated IGHV, 56%. 147 (92%) and 149 (94%) pts completed planned tx with I and V, respectively. Median time on study was 27.9 mo (range, 0.8–33.2). With fixed-duration I+V, CR rate was 55% (95% CI 48–63) in the overall population and was consistent across high-risk subgroups. Of the 88 pts who achieved CR, 78 (89%) had durable CR (duration $1 y); 1 died 7 mo af- ter CR, and 9 with <1 y follow-up were not evaluable. ORR was 96%. Best uMRD response was achieved in 77% of pts in peripheral blood (PB) and 60% of pts in bone marrow (BM). 24-mo PFS was 95%; 24-mo OS was 98%. Results were similar in pts without del(17p) (n=136) (Table). In pts with del(17p)/TP53 mutation (n=27), CR rate was 56%, uMRD rate was 81% (PB) and 41% (BM), and 24- mo PFS was 84% (95% CI 63–94). Of 34 pts with high baseline TLS risk based on tumor burden, 32 (94%) shifted to medium or low risk after I lead-in; no TLS occurred. AEs were primarily grade 1/2. Most common grade 3/4 AEs were neutropenia (33%), hypertension (6%), and neutrophil count de- creased (5%). AEs led to discontinuation of I in 4% and V in 2%. Conclusions: First-line I+V is an all- oral, once-daily, chemotherapy-free, fixed-duration regimen that provides deep, durable responses in pts with CLL/SLL, including those with genomic high-risk features. CR, uMRD rates, PFS, and OS ap- pear favorable. The safety profile of I+V was consistent with known AEs for each agent; no new safety signals were identified. Clinical trial information: NCT02910583. Research Sponsor: Pharmacyclics LLC, an AbbVie Company. Pts without del(17p) All pts Efficacy n=136 N=159 CR/CRi, n (%) 76 (56) 88 (55) Durable CR/CRi, n/N (%)* 66/76 (87) 78/88 (89) ORR, n (%) 130 (96) 153 (96) uMRD in PB, n (%) 104 (76) 122 (77) uMRD in BM, n (%) 84 (62) 95 (60) 24-mo PFS rate, % (95% CI) 96 (91-98) 95 (90-97) 24-mo OS rate, % (95% CI) 98 (93-99) 98 (94-99) *Progression-free $12 cycles from first CR.
Load more

Recommended publications
  • 2015 Post-ASH Report
    Datamonitor Healthcare Trialtrove Biomedtracker Pharma intelligence | Pharma intelligence | Pharma intelligence | 2015 Post-ASH Report RACHEL MEIGHAN-MANTHA Principal Analyst, Citeline JOSEPH HEDDEN Senior Analyst, Datamonitor Healthcare Summary Profiled themes at the 57th Annual Meeting and Exposition of the American Society of Hematology (ASH), held December 5-8, 2015, in Orlando, Florida, included Genomic Profiling and Chemical Biology, Genome Editing and Gene Therapy, Epigenetic Mechanisms, Immunologic Treatments, Stem Cell Biology and Regenerative Medicine and Preventing Venous Thromboembolic Disease. This report will mainly focus on the theme of Immunologic Treatments because of the importance and popularity of immunotherapies for many different hematological cancers. Also covered in this report are the results from pivotal trials presented at ASH, as well as highlights from other drugs/therapies of interest. In addition, we felt it was important to cover first-in-human trials since (hopefully) some of these drugs/therapies will be in pivotal trials in a few years. At the end of the report, we’ve included a section showcasing drugs that had top- line results presented at ASH, followed by a list of other data presentations supplied by BioMedTracker (BMT). Accompanying links to BioMedTracker events along with changes to the drugs’ likelihood of approval (LOA) are also provided throughout the report. Finally, additional supplemental material related to ASH is listed in the Appendix. 2 Datamonitor Healthcare Trialtrove Biomedtracker
    [Show full text]
  • Tanibirumab (CUI C3490677) Add to Cart
    5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor
    [Show full text]
  • Pre-Clinical Specificity and Safety of UC-961, a First-In-Class Monoclonal Antibody Targeting ROR1
    SOHO Supplement 2015 Pre-clinical Specificity and Safety of UC-961, a First-In-Class Monoclonal Antibody Targeting ROR1 Michael Y. Choi,1 George F. Widhopf II,1 Christina C.N. Wu,1 Bing Cui,1 Fitzgerald Lao,1 Anil Sadarangani,1,2 Joy Cavagnaro,3 Charles Prussak,1 Dennis A. Carson,1 Catriona Jamieson,1,2 Thomas J. Kipps1 Abstract Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncoembryonic antigen. Because of its expression on the cell surface of leukemia cells from patients with chronic lymphocytic leukemia (CLL), but not on normal B-cells or other postpartum tissues, ROR1 is an attractive candidate for targeted therapies. UC-961 is a first-in-class humanized monoclonal antibody that binds the extracellular domain of ROR1. In this article we outline some of the preclinical studies leading to an investigational new drug designation, enabling clinical studies in patients with CLL. Clinical Lymphoma, Myeloma & Leukemia, Vol. 15, No. S1, S167-9 ª 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Keywords: AKT, cancer stem cell, Cirmtuzumab, CLL, Wnt receptor Receptor Tyrosine Kinase-Like normal B lymphocytes.5,6 Analysis of autoantibodies produced Orphan Receptor 1 Is an by patients immunized with autologous leukemia cells transduced Oncoembryonic Antigen Not to express CD154 identified that these autoantibodies recognized Expressed by Normal Postpartum ROR1 protein on the leukemia cell surface.7 Functional studies Tissues
    [Show full text]
  • Role of Non-Coding Rnas in the Development of Targeted Therapy and Immunotherapy Approaches for Chronic Lymphocytic Leukemia
    Journal of Clinical Medicine Review Role of Non-Coding RNAs in the Development of Targeted Therapy and Immunotherapy Approaches for Chronic Lymphocytic Leukemia Felice Pepe 1,2 and Veronica Balatti 1,2,* 1 Department of Cancer Biology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA; [email protected] 2 The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA * Correspondence: [email protected]; Tel.: +1-614-292-0654 Received: 31 December 2019; Accepted: 16 February 2020; Published: 21 February 2020 Abstract: In the past decade, novel targeted therapy approaches, such as BTK inhibitors and Bcl2 blockers, and innovative treatments that regulate the immune response against cancer cells, such as monoclonal antibodies, CAR-T cell therapy, and immunomodulatory molecules, have been established to provide support for the treatment of patients. However, drug resistance development and relapse are still major challenges in CLL treatment. Several studies revealed that non-coding RNAs have a main role in the development and progression of CLL. Specifically, microRNAs (miRs) and tRNA-derived small-RNAs (tsRNAs) were shown to be outstanding biomarkers that can be used to diagnose and monitor the disease and to possibly anticipate drug resistance and relapse, thus supporting physicians in the selection of treatment regimens tailored to the patient needs. In this review, we will summarize the most recent discoveries in the field of targeted therapy and immunotherapy for CLL and discuss the role of ncRNAs in the development of novel drugs and combination regimens for CLL patients. Keywords: CLL; mir-15/16; venetoclax; targeted therapy; immunotherapy 1.
    [Show full text]
  • CLL June 18 2014 Slides
    CLL Current and Emerging Therapies Welcome and Introductions June 18, 2014 CLL Current and Emerging Therapies Thomas J. Kipps, MD, PhD Professor of Medicine Division of Hematology-Oncology Deputy Director for Research UC San Diego Moores Cancer Center La Jolla, CA June 18, 2014 1 CLL Current and Emerging Therapies Disclosures Dr. Kipps does not have any relevant financial relationships with any commercial interests to disclose. June 18, 2014 2 Chronic Lymphocytic Leukemia (CLL) • Clinical course of pts with CLL is highly variable • Many pts are asymptomatic at diagnosis • CLL still is considered incurable with current therapy • Therapy may cause morbidity or mortality • Current recommendations are to withhold therapy until pts develop disease-related – Symptoms (e.g. fatigue, wt. loss) – Complications (e.g. impaired marrow or immune function) CLL Prognostic Markers Mutated vs Unmutated IGHV Genes Overall Survival 100 All Patients 100 Binet Stage A Patients (N=84) (n=62) 80 80 Mutated 60 Mutated 60 Surviving, % Surviving, 40 P=0.001 40 P=0.0008 Surviving, % Surviving, Unmutated 20 Unmutated 20 0 0 0 50 100 150 200 250 300 0 50 100 150 200 250 300 Months Months CLL, chronic lymphocytic leukemia. Hamblin TJ, et al. Blood. 94:1848-1854, 1999 3 Approved Drugs For Treatment of Patients with Chronic Lymphocytic Leukemia • Steroids (e.g. prednisone) Kinase Inhibitors • Ibrutinib • Classic Chemotherapy – Alkylating Agents • Chlorambucil Monoclonal Antibodies • Cyclophosphamide (C) • Alemtuzumab • Bendamustine (B) • Ofatumumab – Purine Analogs •
    [Show full text]
  • 2018 Medicines in Development for Cancer
    2018 Medicines in Development for Cancer Bladder Cancer Product Name Sponsor Indication Development Phase ABI-009 AADi Bioscience non-muscle invasive bladder cancer Phase I/II (nab-rapamycin/mTOR inhibitor) Los Angeles, CA www.aadibio.com ALT-801 Altor BioScience non-muscle invasive bladder cancer Phase I/II (tumor antigen-specific T-cell Miramar, FL www.altorbioscience.com receptor linked to IL-2) NantKwest Culver City, CA ALT-803 Altor BioScience non-muscle invasive bladder cancer Phase II (IL-15 superagonist protein complex) Miramar, FL (BCG naïve) (Fast Track), www.altorbioscience.com NantKwest non-muscle invasive bladder cancer Culver City, CA (BCG unresponsive) (Fast Track) B-701 BioClin Therapeutics 2L locally advanced or metastatic Phase I/II (anti-FGFR3 mAb) San Ramon, CA bladder cancer www.bioclintherapeutics.com Bavencio® EMD Serono 1L urothelial cancer Phase III avelumab Rockland, MA www.emdserono.com (anti-PD-L1 inhibitor) Pfizer www.pfizer.com New York, NY BC-819 BioCanCell Therapeutics non-muscle invasive bladder cancer Phase II (gene therapy) Cambridge, MA (Fast Track) www.biocancell.com Medicines in Development: Cancer ǀ 2018 1 Bladder Cancer Product Name Sponsor Indication Development Phase Capzola® Spectrum Pharmaceuticals non-muscle invasive bladder cancer application submitted apaziquone Henderson, NV (Fast Track) www.sppirx.com Cavatak® Viralytics bladder cancer (+pembrolizumab) Phase I coxsackievirus Sydney, Australia www.viralytics.com CG0070 Cold Genesys non-muscle invasive bladder cancer Phase II (oncolytic immunotherapy)
    [Show full text]
  • Understanding Mantle Cell Lymphoma: Relapsed/Refractory
    Understanding Mantle Cell Lymphoma: Relapsed/Refractory Mantle cell lymphoma (MCL) is a rare type of B-cell non-Hodgkin lymphoma (NHL). It can occur in men and women of any age, but it most commonly affects men over 60 years old. The disease is called “mantle cell lymphoma” because the tumor cells come from white blood cells (B lymphocytes) that are found in the “mantle zone” of the lymph node. By the time a person is diagnosed, MCL is usually present throughout the body, in the lymph nodes, spleen, bone marrow, and gastrointestinal tract. Although patients may not need treatment at the time of diagnosis, MCL usually reacts well to the first treatment. The amount and period of time of the remission (disappearance of signs and symptoms) may be different because of things like lymphoma biology and the kind of treatment given. Most patients will need treatment more than one time. TREATMENT OPTIONS given after a patient’s first therapy, but it may also work well for medically fit patients who have a good response to There are a number of treatment options for the management later therapies. Younger medically fit patients may consider of relapsed/refractory (returns after or no longer responds to allogeneic SCT as a possible cure, but SCT may have more treatment) MCL, and the number of treatment choices is going risks. For more information on transplantation, see the up. The type of treatment recommended depends on several Understanding the Stem Cell Transplantation Process publication things, including what treatments were already given, when the at lymphoma.org/publications.
    [Show full text]
  • FOCUS on NHL/CLL Thursday December 10, 2020 (3 Hrs)
    CONGRESS COVERAGE: ASH 2020 – FOCUS ON NHL/CLL Thursday December 10, 2020 (3 hrs) Agenda is tentative based on late-breakers. Abstracts in orange represent potentially lower-priority material; we will discuss with Dr Kahl about whether to include them. AGENDA Time Topic Presenter 5 min Welcome Brad Kahl, MD DLBCL • 597 “Safety and Efficacy of Induction and Maintenance Avelumab Plus R-CHOP in Patients with Diffuse Large B- Cell Lymphoma (DLBCL): Analysis of the Phase II Avr- CHOP Study”--Eliza A Hawkes • 598 “Phase 1b/2 Study of Vipor (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide) in Relapsed/Refractory B-Cell Lymphoma: Safety, Efficacy and Molecular Analysis”--Christopher Melani • 401 “Single-Agent Mosunetuzumab Is a Promising Safe and Efficacious Chemotherapy-Free Regimen for Elderly/Unfit Patients with Previously Untreated Diffuse Large B‑Cell Lymphoma”--Adam J Olszewski • 2099 “Interim Results of Loncastuximab Tesirine Combined with Ibrutinib in Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma (LOTIS-3)”--Julien Depaus 10 min • 400 “Odronextamab (REGN1979), a Human CD20 x TBC CD3 Bispecific Antibody, Induces Durable, Complete Responses in Patients with Highly Refractory B-Cell Non- Hodgkin Lymphoma, Including Patients Refractory to CAR T Therapy”--Rajat Bannerji • 599 “Polatuzumab Vedotin Plus Venetoclax with Rituximab in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Primary Efficacy Analysis of a Phase Ib/II Study”--Giuseppe Gritti • 33 “Double-Hit Signature with TP53 Abnormalities Predicts Poor Survival in Patients with Germinal Center Type Diffuse Large B-Cell Lymphoma Treated with R- CHOP”--Joo Y Song • 126 “A Once Daily, Oral, Triple Combination of BTK Inhibitor, mTOR Inhibitor and IMiD for Treatment of Relapsed/Refractory Richter’s Transformation and De Novo Diffuse Large B-Cell Lymphoma”--Anthony R.
    [Show full text]
  • Targeting Cancer
    TARGETING CANCER New Science. New Cancer Therapies. New Hope. Company Overview – May 7, 2020 ONCT Corporate Presentation May 7, 2020 FORWARD LOOKING STATEMENTS This presentation includes forward-looking statements (including within the meaning of §21E of the U.S. Securities Exchange Act of 1934, as amended, and § 27A of the U.S. Securities Act of 1933, as amended). Forward looking statements, which generally include statements regarding goals, plans, intentions and expectations, are based upon current beliefs and assumptions of Oncternal Therapeutics, Inc. (“Oncternal,” or the “Company”) and are not guarantees of future performance. Statements that are not historical facts are forward-looking statements, and include statements regarding the expected timing for achieving key milestones, including completing and announcing results of clinical trials of the Company’s product candidates, and the anticipated market potential, duration of patent coverage, and ability to obtain and maintain favorable regulatory designations for the Company’s product candidates and preclinical programs. All forward looking statements are subject to risks and uncertainties, which include, but are not limited to: uncertainties associated with the clinical development and process for obtaining regulatory approval of Oncternal’s product candidates, including potential delays in the commencement, enrollment and completion of clinical trials; inherent risks involved in the commercialization of any product, if approved; the risk that results seen in a case study of
    [Show full text]
  • Copyrighted Material
    127 Index Note: Page numbers in italic refer to figures, those in bold refer to tables. 7.1 see NG2 acute mixed phenotype with t(6;9) 52 α (alpha) 39 leukaemia see mixed with t(8;21)(q22;q22.1) 54, γ (gamma) 39 phenotype acute leukaemia 55, 93, 112 δ (delta) 39 acute monoblastic leukaemia, with t(9;11) or other KMT2A ε (epsilon) 39 case 102, 118–119 rearranged 52 κ (kappa) 38 acute monoblastic/monocytic acute promyelocytic leukaemia, λ (lambda) 38 leukaemia 33 with t(15;17)(q24.1;q21.2) μ (mu) 39 acute monocytic leukaemia, 48–52, 54, 93, 112 case 100, 116–118 acute undifferentiated a acute myeloid leukaemia leukaemia (AUL) 62 abbreviations ix–x, 47, 89 (AML) 48 case 108, 123 acute basophilic leukaemia associated with Down’s adult T‐cell leukaemia/ 14, 36, 55 syndrome 28, 55 lymphoma (ATLL) 74, acute lymphoblastic leukaemia with bi‐allelic CEBPA 92, 94, 112, 113 (ALL) 55–62, 90, 111 mutation 55 aggressive NK‐cell see also B‐lineage acute case 98, 115 leukaemia 76, 91, 111 lymphoblastic leukaemia immunophenotyping of alemtuzumab 27, 73 (B‐ALL) acute myeloid leukaemia ALK1 see CD246 case 103, 119–120 and blastic plasmacytoid ALK‐negative anaplastic large minimal residual disease dendritic cell cell lymphoma 75 (MRD) 77–78 neoplasm 53–54 ALK‐positive anaplastic large therapy‐related 103, 119–120 with inv(3) 52 cell lymphoma 75 T‐lineage acute lymphoblasticCOPYRIGHTED with inv(16) 12, 52, MATERIAL53 ALL see acute lymphoblastic leukaemia (T‐ALL) minimal residual disease leukaemia 60–62, 103–104, 119–120 (MRD) 78 AML see acute myeloid acute mast cell leukaemia with mutated NPM1 leukaemia 20, 23 92, 111 anaplastic large cell lymphoma acute megakaryoblastic with mutated RUNX1 55 75, 95, 113 leukaemia 15, 23, 25, 29, with myelodysplasia‐related case 105, 120 30, 53–54, 55 changes 55 angioimmunoblastic T‐cell with t(1;22)(p13.3;q13.1); not otherwise specified 55 lymphoma 74 RBM15‐MKL1 54, 93 with t(1;22) 92 annexin A1 39 Immunophenotyping for Haematologists: Principles and Practice, First Edition.
    [Show full text]
  • 2019 Biomedtracker Datamonitor Healthcare ASCO Planner
    AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING 2018 Pre-ASCOCHICAGO, Report ILLINOIS • MAY 31 – JUNE 4, 2019 Cover page, paste image over entire page 2019 ASCO Planner May 2018 / 1 Information Classification: General NOT A PRODUCT SPONSORED BY ASCO 2019 ASCO Annual Meeting Planner Friday, May 31 - Oral Presentations Start End Title Drug Company Presenter Abstract # Clinical Science Symposium EGFR and ROS1: Targeting Resistance Location: Hall D1 1:00 PM 2:30 PM Chair - EGFR and ROS1: Targeting Resistance Gregory J. Riely 1:00 PM 2:30 PM Chair - EGFR and ROS1: Targeting Resistance Jose Maria Pacheco 1:00 PM 1:12 PM How Can We Overcome TKI Resistance in EGFR-Mutant NSCLC? Katerina A. Politi 1:12 PM 1:24 PM JNJ-61186372 (JNJ-372), an EGFR-cMet bispecific antibody, in EGFR-driven advanced non-small cell JNJ-61186372 Johnson & Johnson Eric B. Haura 9009 lung cancer (NSCLC). 1:24 PM 1:36 PM Safety and preliminary antitumor activity of U3-1402: A HER3-targeted antibody drug conjugate in U3-1402 Daiichi Sankyo Pasi A. Janne 9010 EGFR TKI-resistant, EGFRm NSCLC. 1:36 PM 1:48 PM Using Antibodies in a TKI World Jessica Ruth Bauman 1:48 PM 2:00 PM Safety and preliminary clinical activity of repotrectinib in patients with advanced ROS1 fusion- repotrectinib Turning Point Byoung Chul Cho 9011 positive non-small cell lung cancer (TRIDENT-1 study). Therapeutics 2:00 PM 2:12 PM cROS1ng Barriers in Resistance Benjamin Besse 2:12 PM 2:30 PM Panel Question and Answer Panel Discussion Oral Abstract Session Genitourinary (Prostate) Cancer Location: Arie Crown Theater 2:45 PM 5:45 PM Chair - Genitourinary (Prostate) Cancer Joshi J.
    [Show full text]
  • This Is an Author Produced Version of a Paper Published in Current Drug Targets
    This is an author produced version of a paper published in Current Drug Targets. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination. Citation for the published paper: Curr Drug Targets. 2015 Sep 30. [Epub ahead of print] Targeting Receptor Tyrosine Kinases using Monoclonal Antibodies: The Most Specific Tools for Targeted-Based Cancer Therapy Shabani, Mahdi ; Hojjat-Farsangi, Mohammad DOI: 10.2174/1389450116666151001104133 Access to the published version may require subscription. Published with permission from: Bentham Science Targeting Receptor Tyrosine Kinases using Monoclonal Antibodies: The Most Specific Tools for Targeted-Based Cancer Therapy Mahdi Shabani 1 and Mohammad Hojjat-Farsangi 2, 3 1 Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran 2 Department of Oncology-Pathology, Immune and Gene therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute, Stockholm, Sweden 3 Department of Immunology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran Corresponding author: Mohammad Hojjat-Farsangi, Ph.D, Assistant Professor, Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden, Tel: +46 8 51 77 43 08, Fax: +46 8 31 83 27, Email: [email protected] Running title: Monoclonal antibodies and RTKs targeted therapy 1 Abstract: Receptor tyrosine kinases (RTKs) family is comprised of different cell surface glycoproteins. These enzymes participate and regulate vital processes such as cell proliferation, polarity, differentiation, cell to cell interactions, signaling, and cell survival. Dysregulation of RTKs contributes to the development of different types of tumors. RTKs deregulation in cancer has been reported for more than 30 RTKs.
    [Show full text]