NCT06827860

Subcutaneous Talquetamab in Elderly Patients With Multiple Myeloma in Early Relapse

A Phase 2 Single-Arm Study of Subcutaneous Talquetamab in Elderly Patients With Multiple Myeloma in Early Relapse

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 23 (estimated)
• Sponsor: Larysa Sanchez · Academic / Other
• Sex: All
• Age: 70 Years
• Healthy volunteers: Not accepted

Summary

Induction therapy approaches in recent years have evolved, now utilizing triple or quadruple drug regimens in the majority of patients. By combining anti-CD38 antibodies, proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and steroids, patients achieve longer remissions with their first- and second-line therapies but also become refractory to most or all three major drug classes earlier. For patients who are refractory to at least 3 of the commonly administered PIs and IMiDs, occurring after 2 lines of therapy in many, the median overall survival is only 5 months. Elderly, frail patients are not often candidates at this point for aggressive therapies like stem cell transplantation and CAR T-cell therapy thus necessitating effective yet tolerable treatments for elderly patients in early relapse (1-3 prior therapy). Talquetamab is a GPRC5DxCD3 bispecific antibody that redirects patients' T cells to myeloma cells which express GPRC5D. In the phase 1 MonumenTAL-1, heavily pretreated patients with a median of 6 prior lines of therapy attained a 70% response rate with 405 μg/kg of subcutaneous (SC) talquetamab. Importantly, subcutaneous talquetamab was found to be tolerable for the treated population, which included 28% of patients aged ≥70, with only three patients experiencing dose-limiting toxicities in the form of grade 3 rashes which responded to steroids. The anti-CD38 antibody daratumumab eliminates CD38-positive T and B regulatory cells, potentiates the activity of bispecific antibodies like talquetamab, and may improve its efficacy when used in combination. The aim of this study will be to assess the efficacy and safety of treating elderly patients with relapsed/refractory multiple myeloma with at least ≥2 prior lines of therapy with subcutaneous talquetamab. Patients who have progressive disease on talquetamab or who fail to respond after 3 cycles will have subcutaneous daratumumab added to their regimen.

Conditions

• Multiple Myeloma in Relapse

Interventions

Type	Name	Description
DRUG	Talquetamab	SC monotherapy starting with three step-up doses followed by the standard 800 μg/kg dose every other week. Cycles will be 28 days long.
DRUG	Daratumumab	SC at the standard dose (weekly for 2 cycles, every other week for 4 cycles, monthly thereafter)

Timeline

• Start date: 2025-11-18
• Primary completion: 2027-01-01
• Completion: 2028-01-01
• First posted: 2025-02-14
• Last updated: 2025-12-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study