What Is Talquetamab?
Talquetamab is an investigational drug, currently being studied in clinical trials for certain blood cancers. It is a type of medication known as a bispecific antibody. Bispecific antibodies are designed to target two different proteins, often one on cancer cells and another on immune cells, to help the body's immune system recognize and fight cancer. By bringing these cells closer, Talquetamab aims to enhance the immune response against cancerous plasma cells in patients with multiple myeloma.
This drug is primarily being investigated for the treatment of multiple myeloma, especially in patients whose disease has returned after treatment (relapsed) or has not responded to previous treatments (refractory). Clinical trials are evaluating its safety and effectiveness, as well as determining the optimal doses and schedules. Talquetamab is being studied in a total of 36 trials, with 18 trials currently recruiting participants. The first trial for Talquetamab began in 2018, and studies are planned as late as 2026, with a total enrollment of approximately 7,100 participants across all studies.
Uses and Conditions Under Study
Talquetamab is primarily being investigated for various forms of multiple myeloma and related blood cancers. The drug's mechanism as a bispecific antibody aims to help the immune system target and eliminate cancerous cells.
- Multiple Myeloma and Relapsed/Refractory Multiple Myeloma: This is a cancer of plasma cells, a type of white blood cell found in the bone marrow. When these cells become cancerous, they can produce abnormal proteins and damage bones. Talquetamab is being studied in 32 trials for multiple myeloma, including cases where the disease has returned (relapsed) or has not responded to previous treatments (refractory). The goal is to provide a new treatment option for patients with challenging forms of this cancer.
- Plasma Cell Leukemia: This is a rare and aggressive form of multiple myeloma where cancerous plasma cells are found in the blood. Talquetamab is being investigated in 1 trial for this condition, suggesting its potential role in managing more advanced plasma cell disorders.
- Hematological Malignancies: This is a broader category that includes cancers affecting the blood, bone marrow, and lymph nodes. Talquetamab is being explored in 2 trials for these types of cancers, indicating a potential wider application beyond just multiple myeloma.
- Post Stem Cell Transplant: In 1 trial, Talquetamab is being studied in patients who have undergone a stem cell transplant. This suggests an investigation into its role in managing multiple myeloma in the context of post-transplant care, potentially to prevent relapse or treat residual disease.
Dosing
Talquetamab is administered through injection, with both intravenous (IV) and subcutaneous (SC) routes of administration being studied in clinical trials. The specific dose and schedule can vary depending on the trial and whether Talquetamab is given alone or in combination with other medications.
For subcutaneous administration, some studies have investigated a dose escalation schedule. For example, one trial administered Talquetamab on Days 1, 3, and 5, with doses of 0.01 mg/kg on Day 1, 0.06 mg/kg on Day 3, and 0.4 mg/kg on Day 5. This approach allows medical staff to gradually increase the dose until a target treatment dose is reached.
Talquetamab is also being studied in various combinations, such as with daratumumab, iberdomide, dexamethasone, carfilzomib, lenalidomide, pomalidomide, and teclistamab. These combination therapies often involve different dosing regimens and schedules tailored to the specific treatment plan. The aim of these studies is to determine the safest and most effective dose for patients with multiple myeloma and related conditions.
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Side Effects
The most common side effect experienced by patients taking Talquetamab was cytokine release syndrome (CRS), occurring in 76% of patients. This compares to 0% in a placebo group, as CRS is a known effect of this type of therapy.
Other frequently reported side effects included:
- Dysgeusia (taste alteration): 70% of patients experienced this.
- Nail disorders: 55% of patients developed nail-related issues.
- Skin disorders (such as rash): 51% of patients reported skin reactions.
- Weight loss: 49% of patients experienced a decrease in weight.
- Fatigue: 45% of patients reported feeling tired or lacking energy.
In trials without a placebo comparator, other notable side effects included infections (e.g., upper respiratory tract infection in 30% of patients) and neurological toxicity, specifically immune effector cell-associated neurotoxicity syndrome (ICANS), which occurred in 10% of patients. These events were closely monitored due to the nature of Talquetamab's mechanism of action.
Clinical Trial Results
Multiple Myeloma (Relapsed/Refractory)
Clinical trials have evaluated Talquetamab in patients with relapsed or refractory multiple myeloma who had received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. The primary study supporting its use was MonumenTAL-1 (NCT04634552).
In this study, Talquetamab demonstrated significant efficacy. Among patients who received the recommended Phase 2 dose, 73% of patients achieved an overall response, meaning their cancer significantly improved or disappeared. A deeper response, defined as a very good partial response (VGPR) or better, was observed in 58% of patients. This included 35% of patients who achieved a complete response (CR) or better.
The median duration of response (DOR) for patients who responded to treatment was 9.5 months, indicating how long patients continued to benefit from the therapy. For those who achieved a complete response or better, the median DOR was not yet reached, suggesting a potentially longer benefit in this subgroup. These results highlight Talquetamab's ability to induce meaningful and durable responses in a heavily pretreated patient population.
Currently Recruiting Trials
Talquetamab is currently being investigated in a range of clinical trials for patients with multiple myeloma, exploring its potential both as a standalone therapy and in combination with other treatments. These studies aim to understand its safety, effectiveness, and optimal use in different patient populations and disease stages.
- One Phase 1 study, NCT07032714, is enrolling 25 patients with relapsed and refractory multiple myeloma (RRMM) to find the recommended dose of mezigdomide and talquetamab alongside dexamethasone.
- For frail patients with newly diagnosed multiple myeloma, a Phase 2 study, NCT07107529, is comparing daratumumab with either teclistamab or talquetamab, targeting 150 participants.
- Another Phase 1b study, NCT07093554, is evaluating talquetamab as a bridging therapy before cilta-cel in 31 patients with RRMM.
- NCT06827860 is a Phase 2 study focusing on subcutaneous talquetamab monotherapy or in combination with daratumumab for 23 elderly patients with multiple myeloma in early relapse.
- A Phase 1/2 trial, NCT06572605, is combining external beam radiation therapy with talquetamab for 20 patients whose multiple myeloma includes extramedullary disease.
- NCT06993675 is a Phase 2 study for 50 patients with newly diagnosed multiple myeloma, investigating talquetamab and teclistamab to eliminate minimal residual disease (MRD).
- In a Phase 1 trial, NCT06348108, talquetamab is being studied with iberdomide and dexamethasone for 32 patients with relapsed or refractory multiple myeloma.
- Stanford University is sponsoring a Phase 2 study, NCT06461988, to assess talquetamab and lenalidomide as post-stem cell transplant maintenance therapy in 20 patients with multiple myeloma.
- A Phase 2 study, NCT06500884, is evaluating preventive treatments for GPRC5D-related oral events in 210 patients receiving talquetamab for multiple myeloma.
- NCT06505369 is a Phase 2 study for 50 transplant-eligible patients with newly diagnosed MM, evaluating talquetamab and teclistamab as consolidation therapy.
- A large Phase 3 study, NCT06208150, is comparing talquetamab plus pomalidomide or talquetamab plus teclistamab against standard regimens in 795 patients with relapsed or refractory multiple myeloma who have received previous anti-CD38 antibody and lenalidomide treatment.
- The REVIVE Study, NCT06100237, is a Phase 2 immuno-oncology study for 50 patients with high-risk smoldering myeloma, exploring teclistamab or talquetamab in combination with daratumumab.
- NCT05972135 is a Phase 2 study evaluating the feasibility of outpatient administration of teclistamab or talquetamab for 100 patients with multiple myeloma.
- For patients who have received BCMA CAR T-Cell therapy, a Phase 2 study, NCT06066346, is investigating talquetamab in 17 patients with multiple myeloma.
- The MajesTEC-5 study, NCT05695508, is a Phase 2 trial evaluating various teclistamab-, talquetamab-, and JNJ-79635322-based combination regimens in 160 newly diagnosed transplant-eligible patients with multiple myeloma.
- A significant Phase 3 study, NCT05552222, is comparing teclistamab plus daratumumab and lenalidomide, or talquetamab plus daratumumab and lenalidomide, against daratumumab, lenalidomide, and dexamethasone in 1590 newly diagnosed patients with multiple myeloma.
- NCT04634552 is a Phase 2 study evaluating the efficacy and safety of talquetamab in 510 participants with relapsed or refractory multiple myeloma.
- An observational study, NCT06855121, is also underway in Norway to study the effectiveness and complications of novel immunotherapies, including Talquetamab, in routine care for 400 patients with multiple myeloma, plasma cell leukemia, and AL amyloidosis.
Where to Participate
Clinical trials for Talquetamab are actively recruiting patients across a broad geographical area, with study sites located in 35 states and 96 cities. The top recruiting locations include:
- New York, New York (9 sites)
- Cleveland, Ohio (5 sites)
- New Haven, Connecticut (4 sites)
- Cincinnati, Ohio (4 sites)
- Denver, Colorado (3 sites)
- Seattle, Washington (3 sites)
- Duarte, California (3 sites)
- Salt Lake City, Utah (3 sites)
- Louisville, Kentucky (3 sites)
- Richmond, Virginia (3 sites)
Eligibility criteria for most Talquetamab trials typically require participants to be between 18 and 70 years of age. These studies are designed for patients with specific medical conditions, and healthy volunteers are not being recruited.
Development Timeline
The development journey for Talquetamab began with its first clinical trial initiated on January 16, 2018. Early in its pipeline, Talquetamab was explored for conditions such as IBS-C and hyperphosphatemia, indicating an initial broad scope of investigation.
However, the focus of Talquetamab's development quickly shifted and expanded significantly into the realm of hematological malignancies, particularly multiple myeloma (MM). The drug's pipeline grew to include various stages and types of MM, such as relapsed or refractory multiple myeloma (RRMM), multiple myeloma with extramedullary disease, and even as a post-stem cell transplant maintenance therapy.
Janssen Research & Development, LLC has been a key driver in this extensive research, sponsoring 15 of the 36 total trials. The drug has progressed through various phases, with 17 Phase 2 studies and 8 Phase 1 studies evaluating its safety and efficacy. More recently, Talquetamab has advanced into 4 Phase 3 trials, a crucial step towards potential widespread clinical use. The ongoing research efforts are projected to continue, with the latest trial expected to conclude on March 30, 2026.