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4079 Preliminary Safety and Anti-Tumor Activity of XmAb13676, an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster III
Hematology Disease Topics & Pathways:
Biological, Diseases, Follicular Lymphoma, antibodies, CRS, Therapies, Lymphoma (any), Marginal Zone Lymphoma, CLL, Non-Hodgkin Lymphoma, DLBCL, B-Cell Lymphoma, immunotherapy, Lymphoid Malignancies
Monday, December 9, 2019, 6:00 PM-8:00 PM
Hall B, Level 2 (Orange County Convention Center)

Krish Patel, MD1, Jean-Marie Michot, MD2*, Asher A. Chanan-Khan, MD3, Gilles A. Salles, MD, PhD4, Guillaume Cartron, MD, PhD5*, Frederic Peyrade, MD6*, Reda Bouabdallah7*, Erin G. Reid, MD, MS8, Sheeba K. Thomas, MD9, William G. Wierda, MD, PhD10, David Liebowitz, MD11, John M. Pagel, MD, PhD, DSc1, Vincent Ribrag, MD12, M. Wayne Saville, MD11, Chelsea M. Johnson, BSN11*, Thomas Ly, PhD11* and Tycel J. Phillips, MD13

1Center for Blood Disorders and Stem Cell Transplantation, Swedish Cancer Institute, Seattle, WA
2Gustave Roussy Cancer Campus, Villejuif, France
3Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL
4Lyon-Sud University Hospital Complex, Pierre-Bénite, France
5CHU Montpellier, Montpellier, FRA
6Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France
7Department of Hematology, Institute Paoli-Calmettes, Marseille, France
8Moores University of California, San Diego Cancer Center, La Jolla, CA
9Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
10University of Texas M.D. Anderson Cancer Center, Houston, TX
11Xencor, Inc., San Diego, CA
12Gustave Roussy, Villejuif, France
13University of Michigan Cancer Center, Dexter, MI

Introduction: XmAb13676 is a humanized bispecific antibody that binds both CD20 and CD3 in order to recruit cytotoxic T cells to kill CD20 expressing malignant cells. Interim results of an ongoing first-in-human, dose-escalation study (XmAb13676-01; NCT02924402) in subjects with relapsed/refractory (R/R) non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL) are reported here.

Methods: The study is a first-in-human, multi-center, open-label, phase 1, dose-escalation study in subjects with R/R NHL and R/R CLL with a standard 3 + 3 design. The primary objectives are to determine safety, tolerability, and the maximum tolerated dose (MTD) or recommended dose of XmAb13676. Secondary objectives include preliminary anti-tumor activity and PK/PD of XmAb13676. This study is designed in two parts: Part A, escalating dose cohorts that establish an initial priming dose as part of repeated weekly infusions at a fixed dose in a 28-day cycle; and Part B, with a dosing schedule consisting of a priming dose on C1D1 , established in Part A, followed by escalated dose(s) on subsequent weeks. Cytokine Release Syndrome (CRS) prophylaxis with dexamethasone was mandated prior to each administration of XmAb13676. Treatment was continued for 2 cycles or longer if there was evidence of therapeutic benefit.

Results: At data cut-off, 44 subjects have been treated, 36 with NHL and 8 with CLL.

NHL: Subjects with R/R NHL had a median age of 61.5 years (range 32-89), a median of 3.5 prior therapies (range 1-9) and had been diagnosed a median of 24.6 months (range 6.3-181.2) prior to treatment in the study. Treatment-emergent adverse events (TEAEs) related to treatment occurring in ˃ 3 subjects are shown in Table 1A. Nine treatment-related serious adverse events (SAE) occurred in 6 subjects. The most common treatment-related SAE was CRS, which occurred in 4 (11.1%) subjects with 1 of the events being Grade 4 and the other events being ≤ Grade 2. Treatment responses were assessed by the Lugano criteria or International Working Group criteria for Waldenström Macroglobulinemia (WM). There have been 7 objective responses: 2 complete responses (CR; DLBCL), 1 Very Good PR (VGPR; WM), and 4 partial responses (PR; 1FL, 3 DLBCL) at doses of 20-125 µg/kg. In the efficacy-evaluable population, at doses of 80-125 µg/kg, objective responses were observed in 6/18 patients. A priming dose of 45 µg/kg has been chosen for Part B. An MTD has not been reached and dose escalation is ongoing in Part B in NHL.

CLL: Subjects with R/R CLL had a median age of 76 years (range 62-81), a median of 4.5 prior therapies (range 2-6) and had been diagnosed a median of 76.1 months (range 17.5-328.9) prior to treatment in the study. Treatment-related TEAEs occurring in ˃ 1 subject are shown in Table 1B. Three treatment-related serious adverse events (SAE) occurred in 2 subjects. The treatment related SAEs were CRS (Grade 3), hepatocellular injury (Grade 3), and jaundice cholestatic (Grade 2), each of which occurred in 1 (12.5%) subject. There has been 1 CR reported (Richter transformation) in 5 subjects at 20 µg/kg, the highest dose administered thus far. The treatment response was assessed by the Lugano criteria. An MTD has not been reached and dose escalation is ongoing in Part A in CLL.

Conclusions: XmAb13676 demonstrated evidence of clinical activity in heavily pretreated subjects with R/R NHL and R/R CLL treated at doses between 20 and 125 µg/kg. CRS was generally manageable with premedication. The study is ongoing with further optimization of dose and schedule.

Disclosures: Patel: AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Pharmacyclics/Janssen: Consultancy, Speakers Bureau; Sunesis: Consultancy. Chanan-Khan: AbbVie: Research Funding; Xencor: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment; Ascentage: Research Funding; Millennium: Research Funding. Salles: Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Amgen: Honoraria, Other: Educational events; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Epizyme: Consultancy, Honoraria; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events. Cartron: Gilead: Honoraria; Jansen: Honoraria; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Sanofi: Honoraria. Thomas: Celgene: Research Funding; Amgen: Research Funding; Xencor: Research Funding; BMS: Research Funding. Wierda: KITE pharma: Research Funding; Sunesis: Research Funding; Miragen: Research Funding; Gilead Sciences: Research Funding; Acerta Pharma Inc: Research Funding; GSK/Novartis: Research Funding; Cyclcel: Research Funding; Loxo Oncology Inc.: Research Funding; AbbVie: Research Funding; Genentech: Research Funding; Juno Therapeutics: Research Funding; Oncternal Therapeutics Inc.: Research Funding; Pharmacyclics LLC: Research Funding; Xencor: Research Funding; Janssen: Research Funding. Liebowitz: Xencor: Employment, Equity Ownership. Pagel: AstraZeneca: Consultancy; Gilead Sciences: Consultancy; Pharmacyclics: Consultancy. Ribrag: MSD: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel, accommodations, and expenses ; Nanostring: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; AZ: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses ; Incyte: Membership on an entity's Board of Directors or advisory committees; ArgenX: Research Funding. Saville: Xencor: Employment, Equity Ownership. Johnson: Xencor: Employment, Equity Ownership. Ly: Xencor: Employment, Equity Ownership. Phillips: Pharmacyclics: Consultancy, Research Funding; Bayer: Consultancy; Abbvie: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Seattle Genetics: Consultancy; Gilead: Consultancy; Incyte: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH