Talquetamab in Relapsed Myeloma Patients

Dr. Ajai Chari presents an abstract on Talquetamab in patients with relapsed refractory multiple myeloma.

Abstract title:

Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Phase 1/2 Results from MonumenTAL-1

Purpose of the trial:

G protein-coupled receptor family C group 5 member D (GPRC5D) has limited expression in normal human tissue but is highly expressed on malignant plasma cells, making it a promising immunotherapy target for patients (pts) with multiple myeloma (MM). Talquetamab is a first-in-class, off-the-shelf, T-cell redirecting bispecific antibody targeting both GPRC5D and CD3 receptors. MonumenTAL-1 is a phase 1/2 trial (NCT03399799/NCT04634552) of talquetamab in pts with RRMM. In phase 1 of MonumenTAL-1, collective safety, efficacy, pharmacokinetic (PK), and pharmacodynamic (PD) data supported selection of 2 recommended phase 2 doses (RP2Ds) for talquetamab: 0.405 mg/kg subcutaneous (SC) weekly (QW) and 0.8 mg/kg SC every other week (Q2W). Here, we report results for pts treated at these RP2Ds in phase 1 and 2 of MonumenTAL-1.

Video summary:

Eligible pts in phase 1 had measurable MM and had progressed on or were intolerant to standard therapies. Pts in phase 2 had received ≥3 prior lines of therapy (LOT), including ≥1 proteasome inhibitor, ≥1 immunomodulatory drug, and ≥1 anti-CD38 monoclonal antibody (ie, triple-class exposed). In phase 1, 0.405 mg/kg SC QW was a putative RP2D; this was modified to 0.4 mg/kg SC QW in phase 2 for convenience. Phase 1 and 2 data were combined for analysis. Step-up dosing was used to mitigate risk of severe cytokine release syndrome (CRS). Primary endpoint of phase 2 was overall response rate (ORR) per IMWG criteria based on independent committee review. Key secondary endpoints were duration of response (DOR), rate of very good partial response or better (≥VGPR), rate of complete response or better (≥CR), time to response, progression-free survival (PFS), and incidence of AEs. AEs were graded by CTCAE v4.03; CRS events were graded per ASTCT criteria. PD parameters were measured at baseline and through day 1 of cycle 2.

Conclusions:

Talquetamab demonstrated robust efficacy and manageable safety in pts with heavily pretreated RRMM. Additional phase 1 studies (NCT04586426; NCT04108195; NCT05050097) are evaluating talquetamab in combination with other agents in pts with RRMM.

Trial information:

ASH 2022: Abstract #157

Authors:

Ajai Chari, Cyrille Touzeau, Carolina Schinke, Monique C. Minnema, MD, PhD, Jesus Berdeja, MD, Albert Oriol, Niels WCJ Van De Donk, MD, Paula Rodriguez Otero, Elham Askari, Maria-Victoria Mateos, MD, Luciano J. Megala Costa, MD, PhD, Jo Caers, PhD, Leo Rasche, MD, Amrita Y. Krishnan, MD, FACP, Deeksha Vishwamitra, Xuewen Ma, Xiang Qin, Katharine S. Gries, PhD, PharmD, Michela Campagna, Tara Masterson, Brandi Hilder, Jaszianne Tolbert, Thomas Renaud, Jenna D. Goldberg, Christoph Heuck, Jesús San-Miguel, MD, PhD and Philippe Moreau, MD