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OncoMatch/Clinical Trials/NCT06827860

Subcutaneous Talquetamab in Elderly Patients With Multiple Myeloma in Early Relapse

Is NCT06827860 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including Daratumumab and Talquetamab for multiple myeloma in relapse.

Phase 2RecruitingLarysa SanchezNCT06827860Data as of May 2026

Treatment: Daratumumab · TalquetamabInduction 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.

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Extracted eligibility criteria

Cancer type

Multiple Myeloma

Performance status

WHO 0–1

Prior therapy

Min 1 prior line

Must have received: antimyeloma therapy

Relapsed or refractory disease as defined below: Relapsed disease is defined as an initial response to prior treatment, followed by confirmed progressive disease by IMWG criteria >60 days after cessation of treatment. Refractory disease is defined as <25% reduction in M-protein or confirmed progressive disease by IMWG criteria during previous treatment or ≤60 days after cessation of treatment. Received at least 1 prior line(s) of antimyeloma therapy including a minimum of 2 consecutive cycles

Must have received: systemic antimyeloma therapy

Subject must have received at least ≥2 prior line(s) of systemic antimyeloma therapy of treating physician's discretion, including a PI and an IMID

Must have received: proteasome inhibitor

including a PI

Must have received: immunomodulatory agent

including an IMID

Cannot have received: T-cell-engaging antibody

Prior treatment with T-cell-engaging antibodies

Cannot have received: GPRC5D-directed therapy

Any prior GPRC5D-directed therapy

Cannot have received: gene-modified adoptive cell therapy (chimeric antigen receptor modified T cells, NK cells)

Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NK cells) within 3 months

Cannot have received: targeted therapy

Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less.

Cannot have received: epigenetic therapy

Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less.

Cannot have received: investigational drug

treatment with an investigational drug or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less.

Cannot have received: investigational vaccine

Exception: SARS CoV-2 vaccine approved/in use under emergency approval within 4 weeks is allowed

Investigational vaccine other than SARS CoV-2 vaccine approved/ in use under emergency approval within 4 weeks

Cannot have received: live, attenuated vaccine

Live, attenuated vaccine within 4 weeks

Cannot have received: monoclonal antibody

Monoclonal antibody treatment for multiple myeloma within 21 days.

Cannot have received: cytotoxic therapy

Cytotoxic therapy within 21 days.

Cannot have received: proteasome inhibitor

Proteasome inhibitor therapy within 14 days.

Cannot have received: immunomodulatory agent

Immunomodulatory agent therapy within 14 days.

Cannot have received: radiotherapy

Exception: focal radiation within 7 days

Radiotherapy within 14 days or focal radiation within 7 days

Cannot have received: allogenic stem cell transplant

Previous allogenic stem cell transplant

Cannot have received: autologous stem cell transplant

Exception: Received an autologous stem cell transplant ≤12 weeks before the first dose of study drug

Received an autologous stem cell transplant ≤12 weeks before the first dose of study drug

Lab requirements

Blood counts

Hemoglobin: ≥7 g/dL (without transfusion support or erythropoietin use within 7 days before the laboratory test); Platelets: ≥50×10^9/L (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test); Absolute neutrophil count: ≥1.0×10^9/L (prior growth factor support is permitted but must be without support for 7 days for G-CSF or GM-CSF and for 14 days for pegylated GCSF before the laboratory test)

Kidney function

eGFR: ≥30 mL/min based on Modified Diet in Renal Disease Formula calculation

Liver function

AST and ALT: ≤2.5×ULN; Total bilirubin: ≤2.0×ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5×ULN is required)

Have clinical laboratory values meeting the following criteria during the Screening Phase: Hematology Hemoglobin: ≥7 g/dL (≥4.96 mmol/L; without transfusion support or erythropoietin use within 7 days before the laboratory test) Platelets: ≥50×10^9/L (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test) Absolute neutrophil count: ≥1.0×10^9/L (prior growth factor support is permitted but must be without support for 7 days for G-CSF or GM-CSF and for 14 days for pegylated GCSF before the laboratory test) Chemistry AST and ALT: ≤2.5×ULN eGFR: ≥30 mL/min based on Modified Diet in Renal Disease Formula calculation Total bilirubin: ≤2.0×ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5×ULN is required) Serum calcium corrected for albumin: ≤14 mg/dL (≤3.5 mmol/L) or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L;)

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Icahn School of Medicine at Mount Sinai · New York, New York

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