Subcutaneous Talquetamab in Elderly Patients With Multiple Myeloma in Early Relapse

Part of paid clinical trials in New York, New York.

Sponsor
Larysa Sanchez
Study ID
NCT06827860
Phase
PHASE2
Status
Recruiting
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Conditions

  • Multiple Myeloma in Relapse

Eligibility Criteria

Sex
ALL
Age
70 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Talquetamab — DRUG
    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.
  • Daratumumab — DRUG
    SC at the standard dose (weekly for 2 cycles, every other week for 4 cycles, monthly thereafter)

Study Details

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.

Key Dates

Start date
Nov 18, 2025
Status verified
Dec 2025
Primary completion
Jan 31, 2027
Completion
Jan 31, 2028

Study Design

Enrollment
23 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Talquetamab SC monotherapy
    In part 1, patients will receive 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. Response will be assessed monthly according to IMWG criteria, and patients who have PD after completing at least 1 cycle of talquetamab or who fail to attain ≥ PR after completion of cycle 3 will proceed to part 2 only if not previously refractory to an anti-CD38 monoclonal antibody. Patients refractory to an anti-CD38 mAb will not be allowed in Part 2. patients who are refractory to an anti-CD38 mAb and PD at any point will be taken off study and not proceed to Part 2. patients who are refractory to an anti-CD38 mAb and achieve a response \<PR after 3 cycles (stable disease or minimal response) will continue on talquetamab monotherapy until PD or be taken off study per investigator discretion if it is deemed that subject will not continue to derive clinical benefit from talquetamab monotherapy.
  • Experimental: Talqeutemab SC + Daratumumab SC
    For participants who proceed to part 2, talquetamab will be continued at 800 μg/kg every other week but daratumumab will be initiated at the standard dose (weekly for 2 cycles, every other week for 4 cycles, monthly thereafter). In part 2, participants will continue talquetamab and daratumumab until PD, unacceptable toxicity or other reasons for discontinuing treatment, withdrawal from study. Patients in part 1 and part 2 who achieve VGPR or better after receiving at least 4 cycles of talquetamab in the respective part can be transitioned to every 4 week dosing.

Primary Outcome Measure

Objective Response Rate (ORR) [ Time Frame: Completion of part 1 of the study after completion of 3 cycles (each cycle is 28 days each) or until PD, whichever occurs first. ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Icahn School of Medicine at Mount SinaiNew YorkNew York10029
Erick Herrscher, MBA
[email protected]
(212) 241-8615
Nicole Devito, BSc
[email protected]
(212) 824-7367
Larysa Sanchez (PRINCIPAL_INVESTIGATOR)

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