Subcutaneous Talquetamab in Elderly Patients With Multiple Myeloma in Early Relapse

NCT06827860 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY-24-0079864407564MMY2004
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Talquetemab; Elderly patients; Early relapse; Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR defined as the proportion of patients who achieve ≥PR according to IMWG criteria in the intention-to-treat population in Part 1

  Completion of part 1 of the study after completion of 3 cycles (each cycle is 28 days each) or until PD, whichever occurs first.

Secondary Outcomes (14)

• Time to progression (TTP) for talquetamab monotherapy

  Evaluated continuously until end of study (due to disease progression or death from any cause, whichever comes first), assessed up to 36 months

• Progression-free survival (PFS) for talquetamab monotherapy

  Evaluated continuously until end of study (due to disease progression or death from any cause, whichever comes first), assessed up to 36 months

• Overall survival (OS) for talquetamab monotherapy

  Evaluated continuously until end of study (due to disease progression or death from any cause, whichever comes first), assessed up to 36 months

• Duration of response (DOR) for talquetamab monotherapy

  Evaluated continuously until end of study (due to disease progression or death from any cause, whichever comes first), assessed up to 36 months

• ORR2 with addition of daratumumab

  Evaluated continuously until end of study (due to disease progression or death from any cause, whichever comes first), assessed up to 36 months

Study Arms (2)

Talquetamab SC monotherapy

EXPERIMENTAL

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.

Drug: Talquetamab

Talqeutemab SC + Daratumumab SC

EXPERIMENTAL

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.

Drug: Talquetamab; Drug: Daratumumab

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.

Also known as: JNJ-64407564

Talqeutemab SC + Daratumumab SC; Talquetamab SC monotherapy

Daratumumab DRUG

SC at the standard dose (weekly for 2 cycles, every other week for 4 cycles, monthly thereafter)

Talqeutemab SC + Daratumumab SC

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Documented multiple myeloma as defined by the criteria below:
• Multiple myeloma diagnosis according to the IMWG diagnostic criteria
• Measurable disease at screening as assessed by central laboratory, defined by at least 1 of the following:
• Serum M-protein level ≥0.5 g/dL (central laboratory)
• Urine M-protein level ≥200 mg/24 hours (central laboratory)
• Light chain multiple myeloma without measurable M-protein in the serum or the urine: serum immunoglobulin free light chain ≥10 mg/dL or \>100 mg/L (central laboratory) provided the serum free light chain ratio is abnormal (0.22 to 1.52 \[central laboratory\])
• NOTE: Local laboratory results of blood and urine M-protein measurements may be used to determine initial eligibility. Central laboratory results should still be obtained prior to the start of administration of study treatment in order to establish baseline values and confirm the results from the local laboratory.
• 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
• NOTE: Participant must have undergone ≥1 complete cycle of treatment for each regimen, unless progressive disease was the best response to the regimen.
• NOTE: A single line of therapy may consist of 1 or more agents and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of 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
• Subjects who are anti-CD38 monoclonal antibody-naïve, exposed, or refractory will be allowed in Part 1; Only subjects who are anti-CD38 antibody-naïve or exposed will be allowed in Part 2, whereas subjects refractory to anti-CD38 monoclonal antibody will not be allowed in Part 2
• 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: ≥50×109/L (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test) Absolute neutrophil count: ≥1.0×109/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;)

You may not qualify if:

• Any potential subject who meets any of the following criteria will be excluded from participating in the study:
• Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the talquetamab and daratumumab Investigator's Brochure and appropriate prescribing information).
• Prior treatment with T-cell-engaging antibodies
• Prior antitumor therapy as follows, prior to the first dose of study drug:
• o Any prior GPRC5D-directed therapy
• Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NK cells) within 3 months
• 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.
• Investigational vaccine other than SARS CoV-2 vaccine approved/ in use under emergency approval within 4 weeks o Live, attenuated vaccine within 4 weeks
• Monoclonal antibody treatment for multiple myeloma within 21 days.
• Cytotoxic therapy within 21 days.
• Proteasome inhibitor therapy within 14 days. o Immunomodulatory agent therapy within 14 days. o Radiotherapy within 14 days or focal radiation within 7 days
• Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy.
• Received a maximum cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14-day period before the first dose of study drug.
• Stem cell transplantation:
• Previous allogenic stem cell transplant

Sponsors & Collaborators

• Larysa Sanchez: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

talquetamab; daratumumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Larysa Sanchez, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicole K DeVito, BSc

CONTACT

(718) 308-9273; nicole.devito@mountsinai.org

Lupita Chen

CONTACT

(718) 308-9447; Lupita.chen@mountsinai.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: The study will utilize a Simon's two stage design with a total sample size of 23 patients. The study will start with a 28-day screening phase followed by a two-part treatment phase. 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. 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.

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: February 14, 2025
• Study Start: November 18, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal. To achieve aims in the approved proposal. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at (Link tbd).

Locations

US (1)