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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for multiple myeloma, a cancer affecting plasma cells, particularly when it spreads to soft tissues outside the bones. The trial combines external beam radiation therapy (a form of x-ray treatment) with talquetamab (also known as Talvey), a medication that targets and blocks cancer growth. The goal is to determine if this combination is safe and effective. Individuals with multiple myeloma and extramedullary disease (cancer spread beyond bones) who experience pain or discomfort from these cancerous growths may be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and assess its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that talquetamab is generally well-tolerated by patients with multiple myeloma. Research indicates that 78.8% of patients experienced mild to moderate side effects, such as skin reactions or changes in taste. More serious side effects, like infections, were less common, occurring in about 36% of patients, mostly affecting the respiratory tract. One report noted a possible treatment-related death, but such cases are rare.

Studies consider external beam radiation therapy (EBRT) a safe treatment option for multiple myeloma. Some patients might experience common side effects like skin irritation, tiredness, or nausea. However, combining EBRT with other treatments has not shown additional safety concerns.

Overall, both talquetamab and EBRT have been studied separately and have manageable side effects. The ongoing trial aims to better understand their combined safety in treating multiple myeloma with extramedullary disease. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about talquetamab for multiple myeloma because it works differently from standard treatments like proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Talquetamab is a bispecific antibody that targets GPRC5D, a novel target on myeloma cells, along with CD3 on T-cells, directing the body's immune system to attack the cancer more effectively. Additionally, talquetamab is administered subcutaneously, which can be more convenient and less invasive than traditional intravenous therapies. This unique mechanism and delivery method could offer new hope for patients who have exhausted other treatment options.

What evidence suggests that this trial's treatments could be effective for multiple myeloma with extramedullary disease?

Research has shown that talquetamab, which participants in this trial will receive, holds promise for treating multiple myeloma. In one clinical trial, 73% of patients responded well to talquetamab, with many maintaining improvement for at least 9 months. Another study found that patients experienced better symptoms and quality of life. External beam radiation therapy (EBRT), also part of this trial, significantly relieves pain in multiple myeloma, with up to 100% of patients reporting pain relief. Combining talquetamab with EBRT in this trial may enhance treatment effectiveness for extramedullary disease, a challenging aspect of multiple myeloma. ^{1 2 3 6 7}

Who Is on the Research Team?

Scott R Goldsmith

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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

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

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

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4332323/

Current Role of Radiation Therapy for Multiple Myeloma The efficacy of RT in palliating pain is very high, and several studies have reported a 75–100% range of pain control with a relatively short course of RT (2–4, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4391087/

Effects of Radiotherapy in the treatment of multiple myeloma Radiotherapy resulted in complete local pain relief in 31% and partial local pain relief in 54% of the patients. ... The same variables were ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01091883

NCT01091883 | Study Comparing the Safety and ... This study will compare the safety and effectiveness of MR Guided Focused Ultrasound and External Beam Radiation for treatment of metastatic bone tumors or ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1529943023033831

Fracture rate after conventional external beam radiation ... This study demonstrated that new or progressed VCFs occurred in 30.7% of patients within 3 years, in a total of 11.2% of vertebrae.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06707

External Beam Radiation Therapy in Combination with ... Combining EMD-directed EBRT with talquetamab may be safe, tolerable, and/or effective in treating multiple myeloma patients with extramedullary disease.

6. mdpi.com mdpi.com/2072-6694/15/11/2909

Radiotherapy in Combination with Systemic Therapy for ... Radiotherapy is a safe component of the multimodal therapy of multiple myeloma. The combination of radiotherapy and systemic therapy did not lead to a ...

7. patientpower.info patientpower.info/multiple-myeloma/treatments/radiation-for-multiple-myeloma

Radiation for Multiple Myeloma Treatment Side Effects of Total Body Radiation Therapy · Diarrhea · Esophagitis · Fatigue · Skin irritation or burns · Hair loss · Nausea and vomiting.