Limited-duration Teclistamab for Multiple Myeloma

Overseen By Alfred Garfall, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center at Penn Medicine

Must be taking: Teclistamab

Disqualifiers: Systemic amyloidosis, POEMS syndrome, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 1

Duration: 6-9 months

75 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single-arm, non-inferiority study in which patients who have achieved a very good partial response (VGPR) or better, according to International Myeloma Working Group (IMWG) response criteria, following 6 to 9 months of treatment with teclistamab, a B-cell maturation antigen (BCMA)-directed T-cell engager (anti-BCMAxCD3 bispecific antibody), will be offered monitored drug discontinuation. Teclistamab is typically dosed on a regular schedule (every 1-4 weeks) indefinitely until disease progression ("continuous therapy"). Here, a limited-duration regimen will be studied in which patients achieving ≥VGPR after 6-9 months of standard teclistamab dosing will discontinue therapy and resume if laboratory or clinical parameters suggest early disease progression ("limited-duration therapy"). Patients will enter the clinical trial protocol after completing 6-9 months of standard teclistamab monotherapy and achieving ≥VGPR. The study's hypothesis is that the failure probability six months after stopping teclistamab in this patient population will be non-inferior compared to that of historical controls treated with continuous therapy. Reducing drug exposure may be beneficial by reducing risk of infection and reducing anti-BCMA selective pressure toward generation of BCMA-negative relapses. Analysis of minimal residual disease (MRD), tumor features, and bone marrow microenvironment parameters, which will be pursued as exploratory correlative analyses in this study, may identify factors that predict durable response to limited-duration therapy and thereby enable more precise selection of patients likely to benefit from this approach. A subset of patients will be enrolled on a biomarker study for analysis of these exploratory endpoints.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It mainly focuses on the use of teclistamab, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug teclistamab for multiple myeloma?

Teclistamab has shown effectiveness in treating multiple myeloma, with a pivotal trial demonstrating an overall response rate of more than 60% in patients who had already undergone several treatments. It works by activating the immune system to target and destroy cancerous plasma cells, and it has been approved by the FDA for use in patients with relapsed or refractory multiple myeloma. ^{1 2 3 4 5}

Is teclistamab safe for humans?

Teclistamab has been approved for use in treating multiple myeloma, but it can cause side effects like cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly), infections, and neurotoxicity (nerve damage). These side effects require careful management by healthcare providers. ^{1 2 3 4 6}

How is the drug teclistamab unique for treating multiple myeloma?

Teclistamab is unique because it is a bispecific antibody that simultaneously targets CD3 on T cells and BCMA on multiple myeloma cells, activating the immune system to attack the cancer. It is the first of its kind approved for patients with relapsed or refractory multiple myeloma, especially those who have been heavily pretreated, offering a more tolerable option for elderly patients compared to other treatments. ^{1 2 3 4 6}

Research Team

Alfred Garfall, MD

Principal Investigator

Penn Medicine

Eligibility Criteria

This trial is for adults over 18 with multiple myeloma who've had at least three prior treatments, including a proteasome inhibitor, thalidomide analog, and anti-CD38 antibody. They should have responded well to teclistamab therapy (achieving ≥VGPR) without disease progression when enrolling. Patients must not have systemic amyloidosis or POEMS syndrome and should be in good physical condition.

Inclusion Criteria

I do not have systemic amyloidosis or POEMS syndrome.

I have had 3 or more treatments for my condition.

I received a teclistamab dose within the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive teclistamab for 6 to 9 months until achieving a very good partial response (VGPR) or better

6-9 months

Regular visits every 1-4 weeks

Off Drug Surveillance

Participants stop receiving teclistamab and are monitored for disease progression

6 months

Frequent monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment discontinuation

2 years

Treatment Details

Interventions

• Off Drug Surveillance

Trial Overview The study tests if patients can safely stop taking teclistamab after a very good response instead of continuing indefinitely. Participants will be monitored closely for signs of the cancer returning. The goal is to see if this approach is as effective as continuous treatment while potentially reducing side effects and resistance.

Participant Groups

Group I: Off Drug Surveillance Experimental Treatment 1 Intervention

Participants will stop receiving teclistamab and will be monitored closely for growth of their multiple myeloma. Participants will restart teclistamab if their multiple myeloma starts to grow.

Off Drug Surveillance is already approved in European Union, United States for the following indications:

Approved in European Union as Tecvayli for:

• Relapsed or refractory multiple myeloma

Approved in United States as Tecvayli for:

• Relapsed or refractory multiple myeloma in adults who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Findings from Research

Teclistamab-cqyv is a bispecific T-cell engager antibody that effectively activates the immune system to target multiple myeloma cells, showing an overall response rate of over 60% in heavily pretreated patients.

The side effect profile of teclistamab-cqyv is more tolerable compared to other BCMA-targeted therapies, making it a suitable treatment option for elderly patients with relapsed or refractory multiple myeloma, and it has received FDA approval for use as monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab-cqyv: The First Bispecific T-Cell Engager Antibody for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma. Hua, G., Scanlan, R., Straining, R., et al.[2023]

Teclistamab-cqyv is an FDA and EMA-approved bispecific antibody that effectively targets multiple myeloma (MM) by engaging T cells to attack cancer cells, showing a 60% overall response rate in heavily pretreated relapsed/refractory patients.

This treatment is specifically designed for patients who have undergone at least three prior therapies and have shown disease progression, highlighting its role in advanced stages of MM where other treatments have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab-cqyv in multiple myeloma. Martino, EA., Bruzzese, A., Labanca, C., et al.[2023]

Teclistamab has demonstrated strong anti-myeloma activity in patients who have severe renal impairment, indicating its potential effectiveness in a challenging patient population.

The study highlights the importance of evaluating treatments like teclistamab for their efficacy in patients with specific health conditions, such as renal issues, which can complicate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab in patients with multiple myeloma and impaired renal function. Joiner, L., Bal, S., Godby, KN., et al.[2023]

Teclistamab, a bispecific antibody targeting CD3 and BCMA, has received conditional approval in the EU and full approval in the US for treating adult patients with relapsed or refractory multiple myeloma after multiple prior therapies.

The approvals are based on its efficacy in patients who have undergone at least three to four previous treatments, including specific types of therapies, highlighting its role as a treatment option for difficult-to-treat cases of multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab: First Approval. Kang, C.[2022]

Teclistamab, a bispecific antibody targeting B-cell maturation antigen and CD3, has shown promising efficacy in treating relapsed/refractory multiple myeloma, with the recommended Phase II dose established at 1.5 mg/kg subcutaneously, which maintains drug levels above the effective concentration needed for maximum cytotoxicity.

The study utilized pharmacokinetic modeling to predict effective dosing ranges, confirming that doses of 0.27 mg/kg and 0.72 mg/kg intravenously, as well as 0.72 mg/kg subcutaneously, achieved serum concentrations that correlate with effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational Modeling Predicts Efficacious Therapeutic Dosing Range of Teclistamab for Multiple Myeloma. Girgis, S., Lin, SXW., Pillarisetti, K., et al.[2022]

Teclistamab is the first bispecific antibody approved for treating relapsed or refractory multiple myeloma, showing impressive efficacy in heavily pretreated patients, making it a promising option in this challenging area of treatment.

While teclistamab offers significant benefits, it also has notable adverse effects such as cytokine release syndrome, infections, and neurotoxicity, requiring careful management and precautions by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab for Multiple Myeloma: Clinical Insights and Practical Considerations for a First-in-Class Bispecific Antibody. Pan, D., Richter, J.[2023]

References

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

Teclistamab-cqyv: The First Bispecific T-Cell Engager Antibody for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Teclistamab-cqyv in multiple myeloma. [2023]

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

Teclistamab in patients with multiple myeloma and impaired renal function. [2023]

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

Teclistamab: First Approval. [2022]

5. France pubmed.ncbi.nlm.nih.gov

Translational Modeling Predicts Efficacious Therapeutic Dosing Range of Teclistamab for Multiple Myeloma. [2022]

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

Teclistamab for Multiple Myeloma: Clinical Insights and Practical Considerations for a First-in-Class Bispecific Antibody. [2023]