Forimtamig's Effect on T-cells in Relapsed Myeloma Patients

Dr. Carmelo Carlo-Stella presents the updated intravenous and subcutaneous results from a Phase I dose escalation study of Forimtamig, a GPRC5DxCD3 T-cell engaging bispecific antibody with relapsed/refractory multiple myeloma patients

Abstract title:

RG6234, a GPRC5DxCD3 T-Cell Engaging Bispecific Antibody, Is Highly Active in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Updated Intravenous (IV) and First Subcutaneous (SC) Results from a Phase I Dose-Escalation Study

Purpose of the trial:

Despite advances in treatment, almost all pts with newly diagnosed multiple myeloma (MM) eventually relapse and progression-free survival decreases with each subsequent line of therapy. New treatments that target novel antigens and/or have novel mechanisms of action (MOAs) are needed. GPRC5D is a G-protein coupled receptor that is overexpressed on malignant plasma cells. Expression on normal tissue is limited to skin (hair follicles and eccrine glands) and testis (seminiferous tubules). In a Phase I study (NCT04557150), Forimtamig (RG6234), a GPRC5DxCD3 T-cell engaging bispecific antibody with a novel 2:1 configuration, was highly active in pts with RRMM and had a safety profile consistent with its MOA and target distribution when given IV (Hasselbalch Riley et al. EHA 2022). We report updated IV and first SC results.

Video summary:

All pts had RRMM for which no established therapy was available, appropriate or tolerable and had received ≥1 prior IMiD and ≥1 prior PI. Prior CAR T-cells, antibody–drug conjugates and bispecific antibodies were allowed. RG6234 was initiated with step-up dosing, reaching the target dose 2 weeks after the initial step dose, and was given for up to 1 year unless disease progression or unacceptable toxicity occurred. All pts who received RG6234 in the dose-escalation phase of the study were included in the analysis (IV dose range: 6–10000µg; SC dose range: 30–7200µg).

Conclusions:

Forimtamig (RG6234) is highly active in pts with heavily pretreated RRMM when administered IV or SC. AEs are consistent with its MOA and target distribution. Evaluation and optimization of IV and SC dosing is ongoing.

Trial information:

ASH 2022: Abstract #161 (https://ash.confex.com/ash/2022/webprogram/Paper157988.html)

Authors:

Carmelo Carlo-Stella, MD, PhD, Rita Mazza, MD, Salomon Manier, MD, PhD, Thierry Facon, Sung-Soo Yoon, MD, PhD, Youngil Koh, MD, PhD, Simon J Harrison, MD, Jeremy Er, MD, Antonio Pinto, MD, Francesco Volzone, MD, Giulia Perrone, MD, Paolo Corradini, MD, Titouan Cazaubiel, MD, Cyrille Hulin, Cyrille Touzeau, Philippe Moreau, MD, Enrique M. Ocio, Carmen Maria Montes Gaisan, MD, Rakesh Popat, MD, PhD, Sarah Leong, MD, Fritz Offner, MD, PhD, Paula Rodriguez Otero, Ana Alfonso-Pierola, MD, PhD, Ann-Marie E Bröske, Iryna Dekhtiarenko, PhD, Hans-Joachim Helms, PhD, Sara Belli, PhD, Eva Rossmann, MD, PhD, Tanja Fauti, PhD, Jan Eckmann, Tom Moore, MD, Meike Schneider, MD, Wolfgang Jacob, PhD, Martin Weisser, MD, PhD, Martin Hutchings, MD, PhD and Caroline Hasselbalch Riley, MD, PhD