Radiation Therapy + Talquetamab for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: City of Hope Medical Center

Must be taking: Immunomodulatory agents, Proteasome inhibitors, Anti-CD38 antibodies

Must not be taking: Corticosteroids, GPRC5D therapy

Disqualifiers: Active infection, Severe asthma, Cardiac conditions, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial tests the safety and effectiveness of extramedullary disease (EMD)-directed external beam radiation therapy (EBRT) in combination with talquetamab for the treatment of multiple myeloma patients with extramedullary disease. Extramedullary disease in multiple myeloma involves the infiltration of organs and soft tissues by malignant plasma cells and has proven difficult to treat. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink cancers. EBRT is a type of radiation therapy that delivers high-energy beams to the cancer from outside of the body. In this trial, the EBRT will be directed to a site of extramedullary disease. Talquetamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Combining EMD-directed EBRT with talquetamab may be safe, tolerable, and/or effective in treating multiple myeloma patients with extramedullary disease.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, there are specific time requirements for stopping certain cancer treatments before joining the trial, such as waiting 21 days after chemotherapy or 28 days after certain cell therapies.

What data supports the effectiveness of the drug Talquetamab for treating multiple myeloma?

Research shows that nearly three-quarters of patients with relapsed or hard-to-treat multiple myeloma experienced significant benefits from Talquetamab in a clinical trial. This drug works by targeting specific proteins on cancer cells and activating the body's immune response to fight the cancer. ^{1 2 3 4 5}

Is the combination of radiation therapy and Talquetamab safe for humans?

The safety of combining radiation therapy with different immunotherapies has been studied, but specific safety data for Talquetamab with radiation therapy is not available in the provided research. However, radiation therapy has been safely combined with other immunotherapies in clinical trials for various cancers. ^{6 7 8 9 10}

What makes the drug Talquetamab unique for treating multiple myeloma?

Talquetamab is unique because it is a first-in-class bispecific antibody that targets GPRC5D, a protein found on cancerous plasma cells, and recruits T cells to attack these cells, offering a novel approach compared to traditional treatments. It has shown significant anticancer effects in patients with relapsed or refractory multiple myeloma and has a different side effect profile compared to similar therapies. ^{1 2 5 11 12}

Research Team

Scott R Goldsmith

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for multiple myeloma patients with extramedullary disease, where cancer cells have spread to organs and tissues. Participants must meet specific health criteria not detailed here.

Inclusion Criteria

I have multiple myeloma with cancer spread outside the bone marrow.

Agreement to allow the use of archival tissue from diagnostic tumor biopsies

Hemoglobin ≥ 8g/dL

Exclusion Criteria

I have previously received GPRC5D therapy.

I have had radiation therapy on the cancer area I want to target.

I have a heart condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Step-up Period

Patients undergo EMD-EBRT once daily for 5 treatment fractions and receive talquetamab subcutaneously starting after the first fraction and continuing every 2-4 days for up to 3 step-up doses

1 week

5 visits (in-person)

Subsequent Treatment

Patients receive talquetamab subcutaneously on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to a maximum of 13 cycles

Up to 12 months

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Monthly visits (in-person)

Treatment Details

Interventions

• External Beam Radiation Therapy
• Talquetamab

Trial Overview The trial tests a combination of external beam radiation therapy (EBRT) directed at cancer sites and talquetamab, a monoclonal antibody that may inhibit cancer growth, in treating multiple myeloma with extramedullary disease.

Participant Groups

Group I: Treatment (EDM-EBRT, talquetamab) Experimental Treatment 9 Interventions

STEP-UP PERIOD: Patients undergo EMD-EBRT QD for 5 treatment fractions on weekdays (Monday to Friday), and receive talquetamab SC starting after the first fraction of EMD-EBRT and continuing every 2-4 days for up to 3 step-up doses in the absence of unacceptable toxicity. SUBSEQUENT TREATMENT: Starting 2-7 days after step-up dose 3, patients receive talquetamab SC on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to a maximum of 13 total cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT and collection of blood samples throughout the trial and undergo image-guided EMD biopsy at screening and on study. Patients undergo bone marrow biopsy/aspiration at screening and optionally at end of treatment.

Talquetamab is already approved in United States, European Union for the following indications:

Approved in United States as Talquetamab for:

• Relapsed or refractory multiple myeloma

Approved in European Union as Talquetamab for:

• Relapsed or refractory multiple myeloma

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Talquetamab, a bispecific T-cell engager targeting GPRC5D and CD3, has received accelerated approval in the USA and conditional marketing authorization in the EU for treating adults with relapsed or refractory multiple myeloma, highlighting its potential as a new treatment option.

This approval marks a significant milestone in the development of talquetamab, indicating its efficacy and safety in addressing a challenging form of cancer that has not responded to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talquetamab: First Approval. Keam, SJ.[2023]

In the MonumenTAL-1 trial, nearly 75% of the 288 patients with relapsed/refractory multiple myeloma showed significant anticancer effects from the investigational drug talquetamab.

Talquetamab is a first-in-class bispecific antibody that targets GPRC5D on malignant plasma cells while sparing normal cells, effectively activating T cells to mount an immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MonumenTAL Results for Talquetamab in Myeloma. [2023]

Three new bispecific antibodies—teclistamab, elranatamab, and talquetamab—have received accelerated FDA approval for treating relapsed/refractory multiple myeloma, indicating their potential efficacy in this challenging condition.

While these agents show promise, the medical community is currently awaiting results from randomized phase III clinical trials to better understand their effectiveness compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Embarrassment of Riches: Three FDA-Approved Bispecific Antibodies for Relapsed Refractory Multiple Myeloma. Firestone, R., Lesokhin, AM., Usmani, SZ.[2023]

Monoclonal antibodies (MoAbs) like elotuzumab and daratumumab, which target specific antigens (CS1 and CD38) found in over 90% of multiple myeloma patients, show promising anti-myeloma effects, especially when combined with lenalidomide.

The article reviews various emerging MoAbs for multiple myeloma, highlighting their potential in improving treatment outcomes, although multiple myeloma remains largely incurable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic monoclonal antibodies against multiple myeloma]. Kuroda, J.[2019]

Concurrent immunoradiotherapy, combining immune checkpoint inhibitors with radiotherapy, showed a 30% overall response rate in 16 patients with metastatic melanoma who had progressed on nivolumab, with a notable 68.8% response rate in lesions within the radiation fields.

Nivolumab combined with radiotherapy demonstrated a 100% response rate inside the radiation fields, suggesting it may be more effective than ipilimumab in this setting, although some patients experienced grade 3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab. Nomura, M., Otsuka, A., Yoshimura, M., et al.[2019]

In a phase 2 clinical trial involving 17 patients with metastatic triple-negative breast cancer, the combination of pembrolizumab and radiotherapy showed an overall response rate of 17.6%, with three patients achieving complete responses that lasted up to 108 weeks.

The treatment was found to be safe, with the most common side effects being mild dermatitis, and no treatment-related deaths or severe adverse events reported, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer. Ho, AY., Barker, CA., Arnold, BB., et al.[2020]

In a study of 60 patients receiving combined immunotherapy and thoracic radiation therapy (iRT), no patients experienced severe grade ≥4 toxicities, indicating a favorable safety profile for this treatment approach.

While some patients did experience grade 3 toxicities, particularly pulmonary and hematologic issues, the overall short-term safety of iRT suggests it can be administered without significant risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Verma, V., Cushman, TR., Selek, U., et al.[2022]

Pembrolizumab, an immunotherapy targeting PD-1, showed limited effectiveness in a patient with metastatic renal cell carcinoma, highlighting that only 20-40% of patients benefit from such treatments due to individual tumor biology and immune checkpoint diversity.

The patient's rapid disease progression during treatment may be linked to a lack of tumor-infiltrating lymphocytes (TILs) and the specific radiation dose and schedule used, which could affect the tumor microenvironment and the potential synergy with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy. Alexander, GS., Palmer, JD., Tuluc, M., et al.[2022]

The combination of the anti-PD-L1 antibody avelumab with stereotactic body radiation therapy (SBRT) was found to be tolerable in patients with malignant pleural mesothelioma, with no severe (grade 4 or 5) adverse events reported during the study.

Out of 13 patients, the most common side effects included mild to moderate reactions such as infusion-related allergic reactions and fatigue, indicating that while there are some adverse effects, they are manageable and do not pose significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 Safety Study of Avelumab Plus Stereotactic Body Radiation Therapy in Malignant Pleural Mesothelioma. Rimner, A., Adusumilli, PS., Offin, MD., et al.[2023]

Talquetamab, a bispecific antibody targeting GPRC5D and CD3, shows similar efficacy and durability of response in treating relapsed or refractory multiple myeloma compared to teclistamab, the first bispecific antibody approved for this condition.

While talquetamab has a lower incidence of infections than teclistamab, it presents unique side effects related to skin, oral, and nails, yet remains a well-tolerated and effective treatment option for patients with heavily pretreated multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talquetamab in multiple myeloma. Liu, L., Krishnan, A.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Talquetamab: First Approval. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

MonumenTAL Results for Talquetamab in Myeloma. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

An Embarrassment of Riches: Three FDA-Approved Bispecific Antibodies for Relapsed Refractory Multiple Myeloma. [2023]

4. Japan pubmed.ncbi.nlm.nih.gov

[Therapeutic monoclonal antibodies against multiple myeloma]. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Multiple myeloma: monoclonal antibodies-based immunotherapeutic strategies and targeted radiotherapy. [2007]

6. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

A Phase 1 Safety Study of Avelumab Plus Stereotactic Body Radiation Therapy in Malignant Pleural Mesothelioma. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

RR Myelo POINT: A Retrospective Single-Center Study Assessing the Role of Radiotherapy in the Management of Multiple Myeloma and Possible Interactions with Concurrent Systemic Treatment. [2023]

12. Italy pubmed.ncbi.nlm.nih.gov

Talquetamab in multiple myeloma. [2023]