Article Text

Download PDFPDF

448 Lemzoparlimab (TJ011133), an anti-CD47 antibody, with/without dexamethasone plus anti-myeloma regimens for relapsed/refractory multiple myeloma: a phase 1b dose escalation and expansion study
  1. Edward Stadtmauer1,
  2. Lionel Karlin2,
  3. Katja Weisel3,
  4. Moshe Etzion Gatt4,
  5. Ankit Kansagra5,
  6. Gregory Monohan6,
  7. Andrew Yee7,
  8. Shayna Rockow-Magnone8,
  9. Jose Cordero8,
  10. David Hoffman8,
  11. Orlando Bueno8,
  12. Kevin Wu8 and
  13. Cristina Gasparetto9
  1. 1University of Pennsylvania, Philadelphia, PA, USA
  2. 2Centre Hospitalier Lyon Sud, Lyon, France
  3. 3University Medical Center Hamburg-Eppend, Hamburg, Germany
  4. 4Hadassah Medical Center-Hebrew Universit, Jerusalem, Israel
  5. 5University of Texas Southwestern Medical, Dallas, TX, USA
  6. 6University of Kentucky, Lexington, KY, USA
  7. 7Massachusetts General Hospital, Boston, MA, USA
  8. 8AbbVie Inc., North Chicago, IL, USA
  9. 9Duke University Hospital, NC, USA


Background Despite therapeutic advancements for multiple myeloma (MM), most patients with MM develop relapsed/refractory (R/R) disease, which is associated with high mortality and highlights an unmet need for novel treatments.A key characteristic of MM cells is the overexpression of CD47, which downregulates phagocytosis, thereby allowing malignant plasma cells to evade destruction by the immune system. Blocking CD47 with lemzoparlimab, an anti-CD47 monoclonal antibody, may enhance macrophage-mediated anti-tumor activity.This study will characterize the safety, dose-limiting toxicity, and recommended dosing of lemzoparlimab (TJ011133) with or without dexamethasone and combined with other anti-myeloma regimens in patients with R/R MM.

Methods This phase 1b, open-label, dose-escalation and expansion study (NCT04895410) will enroll adults with R/R MM, an Eastern Cooperative Oncology Group Performance Status ≤2, prior treatment history (varies based on treatment arm; Figure 1), and measurable disease (serum monoclonal paraprotein [M-protein] ≥0.5 g/dL, urine M-protein ≥200 mg/24 hours, or serum-free light chain ≥100 mg/L).Patients will be enrolled in 2 phases (escalation and expansion), divided into 4 arms to receive treatment in 28-day cycles (figure 1): (A) lemzoparlimab ± dexamethasone; (B) lemzoparlimab + dexamethasone + pomalidomide (4 mg orally daily [Days 1–21]); (C) lemzoparlimab + dexamethasone + carfilzomib (56 mg/m2 intravenously, 6 doses/cycle [first 2 doses in Cycle 1: 20 mg/m2]); and (D) lemzoparlimab + dexamethasone + daratumumab (1800 mg subcutaneously [Cycle 1, start on Day 2; Cycles 1–2, once weekly; Cycles 3–6, every 2 weeks; Cycles ≥7, Day 1]). Dexamethasone will be administered orally twice weekly at 20 mg for Arm C, and orally or intravenously weekly at 40 mg for other arms. Dose escalation will follow Bayesian optimal interval design. Once maximum tolerated dose/recommended phase 2 dose (RP2D) is determined, patients will be enrolled in the expansion. Treatment discontinuation criteria are: unacceptable toxicity, disease progression, consent withdrawal, or investigator’s discretion.The primary endpoint is determination of the RP2D. Secondary endpoints include safety and efficacy measures. Time-to-event endpoints will be analyzed using the Kaplan–Meier method.

Acknowledgements AbbVie is funding this study and participating in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.Medical writing support was provided by Marta Rossi, PhD, of Fishawack Communications Ltd, and funded by AbbVie.

Trial Registration ClinicalTrials.

gov: NCT04895410

Ethics Approval The protocol, informed consent form(s), recruitment materials, and all patient materials will be submitted to the Independent Ethics Committee/Institutional Review Board for review and approval.

Abstract 448 Figure 1

Study schematic

The dose escalation phase will follow BOIN; it will start with lemzoparlimab (TJ011133) monotherapy at DL1 in Arm A. If DL1 is not tolerated as monotherapy or as combination therapy, DL −1 will be evaluated. Investigation of combination arms will start after evaluation of monotherapy.

Arms A, B, C and D will include patients with R/R MM after progressing on defined therapies and number of prior lines of therapy.

BOIN, Bayesian optimal interval; DL, dose level; MM, multiple myeloma; R/R, relapsed/refractory.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.