What Is Elranatamab?
Elranatamab is an FDA-approved medication for relapsed myeloma patients. It is a bispecific IgG2 kappa monoclonal antibody, meaning it is an engineered protein designed to target two different molecules. Specifically, it acts as a T-cell engager, bringing the body's immune T-cells closer to cancer cells to help destroy them. Elranatamab is also described as an IKZF1/3 degrader, which refers to its ability to break down certain proteins involved in cancer growth. Beyond its approved use, Elranatamab is currently being investigated in clinical trials for various forms of multiple myeloma, including refractory and newly diagnosed cases.
Uses and Conditions Under Study
Elranatamab is primarily studied for the treatment of multiple myeloma, a cancer of plasma cells in the bone marrow. This drug is designed to engage the immune system to fight these cancer cells. Clinical trials are investigating Elranatamab across various stages of the disease, including relapsed refractory multiple myeloma (RRMM), newly diagnosed multiple myeloma, and general multiple myeloma. In total, 48 trials are exploring Elranatamab for these myeloma-related conditions. Additionally, Elranatamab is being studied in 2 trials for AL amyloidosis, a rare condition where abnormal proteins build up in organs, often linked to plasma cell disorders. Overall, 46 clinical trials involving 9,308 participants have been conducted or are ongoing for Elranatamab, with the pharmaceutical company Pfizer sponsoring the majority of these studies. The first trial began in 2019, and the latest is projected to conclude in 2026.
Dosing
Elranatamab is administered as an injection, either intravenously (IV) or subcutaneously (under the skin). Clinical trials are exploring various dosing schedules and combinations. For instance, some studies evaluate Elranatamab (SubQ) Q4W, meaning a subcutaneous injection every four weeks. Researchers are also investigating standard versus reduced frequencies of treatment. Elranatamab is frequently studied in combination with other medications commonly used for multiple myeloma. These combinations include Elranatamab with lenalidomide, bortezomib, and dexamethasone (referred to as elra-RVd lite), or with daratumumab, isatuximab-irfc, or a DC/MM vaccine. Studies also explore Elranatamab Maintenance Therapy following other treatments. The drug is being evaluated for potential self-administration, offering convenience for patients. Various trial arms are comparing Elranatamab alone, or in combination with other agents, to established treatments for multiple myeloma.
Side Effects
In clinical studies, side effects of Elranatamab were observed across different patient groups. No placebo comparison data is available for these open-label trials.
From the NCT05014412 study, which included various parts:
- Cytokine Release Syndrome (CRS) was reported in 20 participants in Part 1, 1 participant in Part 2A Dose Level 1, and 10 participants in Part 2A Dose Level 2. Across all participants in this study, 12 individuals experienced Grade 2 or higher CRS during Cycle 1.
- Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) was reported in 1 participant in Part 1, 1 participant in Part 2A Dose Level 1, 2 participants in Part 2A Dose Level 2, and 14 participants in Part 2B.
- Grade 3 or 4 adverse events were observed in 23 participants in Part 1, 2 participants in Part 2A Dose Level 1, and 16 participants in Part 2B.
- Grade 5 (fatal) adverse events were reported in 5 participants in Part 1, 6 participants in Part 2A Dose Level 2, and 5 participants in Part 2B.
In the NCT04798586 study involving Japanese participants, 2 participants experienced Grade 3 or 4 treatment-emergent adverse events. Hematologic changes, specifically shifts to Grade 3 or 4, included thrombocytopenia in 4 participants, leukopenia in 3 participants, and lymphopenia in 3 participants.
Dose-limiting toxicities (DLTs) were reported in 1 participant in the Phase 1b of the NCT05228470 study (Chinese participants). In the NCT05090566 study, DLTs were observed in 4 participants receiving Elranatamab with Nirogacestat (Dose Level 3) and 2 participants at Dose Level 4A, and in 3 participants receiving Elranatamab with Lenalidomide and Dexamethasone (Dose Level 1).
Clinical Trial Results
Clinical trials have evaluated the efficacy of Elranatamab in patients with multiple myeloma.
MagnetisMM-3 Study (NCT04649359)
This study investigated Elranatamab monotherapy in participants with multiple myeloma refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 monoclonal antibody. The objective response rate (ORR), meaning the percentage of participants whose cancer responded to treatment, was a key outcome:
- In Cohort A, 61.0% of participants achieved an objective response.
- For participants in Cohort A with extramedullary disease (EMD) at baseline, the ORR was 38.5%.
- For participants in Cohort A without EMD at baseline, the ORR was higher at 71.4%.
- The median time to response (TTR) for Cohort A was 1.22 months.
- In Cohort B, 34.4% of participants achieved an objective response, with a median TTR of 1.92 months.
MAGNETISMM-2 Study (NCT04798586)
This study focused on Japanese participants with multiple myeloma. Key efficacy results included:
- An objective response rate (ORR) of 50.0%.
- The median duration of response (DOR) was 12.70 months.
- The median time to response (TTR) was 1.396 months.
- A minimal residual disease (MRD) negativity rate of 25.0% was observed, indicating a deep response to treatment.
Chinese Participants Study (NCT05228470)
In a study involving Chinese participants with refractory multiple myeloma, Elranatamab demonstrated the following objective response rates (ORR):
- In Phase 1b, 37.5% of participants achieved an objective response.
- When combining Phase 1b and Phase 2 data, the ORR was 50.0%.
- In Phase 2 alone, the ORR was 53.3%.
- The median time to response (TTR) ranged from 1.45 months (Phase 2) to 2.04 months (Phase 1b).
Currently Recruiting Trials
Elranatamab is being investigated in numerous clinical trials for multiple myeloma and related conditions, exploring its potential both alone and in combination with other treatments. These studies aim to understand how the drug works, its safety, and its effectiveness for different patient populations.
One Phase 2 study, NCT07382739, sponsored by M.D. Anderson Cancer Center, is enrolling 34 participants with relapsed refractory multiple myeloma (RRMM) who also have extramedullary or paramedullary disease. This trial is exploring whether low doses of radiation therapy can enhance the cancer-killing effect of elranatamab. Another Phase 2 study, NCT07454382, sponsored by Memorial Sloan Kettering Cancer Center, is recruiting 26 individuals to evaluate the combination of elranatamab and cyclophosphamide for people with RRMM who might not respond well to elranatamab alone.
Early-phase trials are also underway, such as NCT07280013, a Phase 1 study sponsored by C4 Therapeutics, Inc., which aims to understand the safety and tolerability of cemsidomide when combined with elranatamab in 60 participants with RRMM. Similarly, Celgene is sponsoring NCT06988488, a Phase 1/2 study enrolling 62 participants to determine the recommended dose and evaluate the safety and preliminary effectiveness of mezigdomide in combination with elranatamab for RRMM.
For individuals newly diagnosed with multiple myeloma, the University of Miami is sponsoring NCT06997081, a Phase 2 study enrolling 104 participants to determine the effects of elranatamab in combination with lenalidomide and dexamethasone (ERd). A large Phase 3 study, NCT06152575, enrolling 492 participants, compares elranatamab to other medicines for multiple myeloma that has returned after prior treatments. Another large Phase 3 study, NCT05623020, is enrolling 1116 participants with newly diagnosed multiple myeloma who are not candidates for transplant, comparing the combination of elranatamab, daratumumab, and lenalidomide with a standard regimen of daratumumab, bortezomib, lenalidomide, and dexamethasone.
Finally, NCT06183489, sponsored by Stichting European Myeloma Network, is a Phase 2 study enrolling 50 participants to evaluate the efficacy and safety of elranatamab in patients with previously untreated high-risk smoldering multiple myeloma.
Where to Participate
Clinical trials for elranatamab are being conducted across a wide geographic area, making participation accessible to many individuals. These studies are currently active at 185 sites in 102 cities across 35 states in the United States.
Some of the cities with the highest number of recruiting sites include:
- Miami, Florida (16 sites)
- Boston, Massachusetts (15 sites)
- New York, New York (9 sites)
- Houston, Texas (9 sites)
- Cincinnati, Ohio (8 sites)
- Indianapolis, Indiana (8 sites)
- Nashville, Tennessee (7 sites)
- Omaha, Nebraska (7 sites)
To be eligible for most of these trials, participants must be between 18 and 75 years of age. All genders are welcome to participate, but these studies are specifically for patients with a medical condition, not healthy volunteers.
Development Timeline
The journey of elranatamab began with its first clinical trial on August 28, 2019, marking the start of its development. Initially, the drug was explored for conditions such as IBS-C and hyperphosphatemia, but its pipeline quickly expanded to focus on various forms of multiple myeloma and related hematological malignancies. Pfizer has been a primary driver of this development, sponsoring 19 of the 46 total trials.
Over time, the scope of investigation broadened to include relapsed refractory multiple myeloma (RRMM), newly diagnosed multiple myeloma, AL amyloidosis, and even high-risk smoldering multiple myeloma. The development program has progressed through all clinical phases, with 19 Phase 2 studies, 7 Phase 1 studies, and 5 Phase 3 studies currently underway or completed. The latest planned trial is set to conclude on March 16, 2026, indicating ongoing research and commitment to understanding the full potential of elranatamab. The total enrollment across all trials has reached 9,308 participants, reflecting a comprehensive effort to evaluate this treatment.