Epcoritamab for Chronic Lymphocytic Leukemia and Richter Syndrome

Overseen By Ingrid C Frey

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

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: Unknown

Duration: Duration not specified

30 Participants Needed

Trial Summary

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's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Epcoritamab for treating Chronic Lymphocytic Leukemia and Richter Syndrome?

While there is no direct data on Epcoritamab for Richter Syndrome, novel immunotherapies, including those targeting immune checkpoints like PD1, have shown promise in treating this condition. Additionally, therapies effective in CLL, such as those targeting BCR or BCL2, are being evaluated for Richter Syndrome, suggesting potential for Epcoritamab, which is a type of immunotherapy. ^{1 2 3 4 5}

What makes the drug Epcoritamab unique for treating Richter Syndrome?

Epcoritamab is unique because it is a bispecific antibody that targets both CD3 on T-cells and CD20 on B-cells, potentially offering a novel mechanism of action compared to traditional chemotherapy, which is often ineffective for Richter Syndrome. ^{1 2 3 4 6}

What is the purpose of this trial?

This correlative study aims to understand the pharmacodynamic effects and clonal dynamics in response to epcoritamab by obtaining and analyzing lymph node, bone marrow, and blood samples from subjects enrolled in GCT3013-03 trial sponsored by Genmab at NIH. Samples will be collected before and at multiple time points during treatment with epcoritamab. National Heart, Lung, and Blood Institute (NHLBI) investigators are experienced in testing samples treated with bsAb2,3 including epcoritamab in an ongoing pre-clinical collaboration with Genmab. Addressing the objectives of this correlative study will advance the science and clinical application of epcoritamab specifically as well as T-cell engaging bsAb in general as an emerging class of immunotherapy for cancer. The study is enrolling by invitation only.

Research Team

Clare C Sun, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria

This trial is specifically for individuals with certain blood cancers, including Chronic Lymphocytic Leukemia and Richter Syndrome. Participants are being invited to join the study, which will involve close monitoring of their response to a new treatment.

Inclusion Criteria

I am willing and able to follow the study rules and attend all required visits.

I can understand and am willing to sign the consent form.

Must be undergoing screening for GCT3013-03

Exclusion Criteria

Not applicable.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive epcoritamab and undergo lymph node, bone marrow, and blood sample collection for pharmacodynamic evaluation

Duration not specified

Multiple visits for sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Epcoritamab

Trial Overview The focus of this trial is on epcoritamab, an experimental medication designed to engage the immune system in fighting cancer. The study involves collecting samples from patients before and during treatment to understand how the drug affects cancer cells.

Participant Groups

Group I: epcoritamab Experimental Treatment 1 Intervention

Samples from subjects receiving epcoritamab on another clinical trial GCT3013-03 will be collected.

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

Approved in United States as Epkinly for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
• Diffuse large B-cell lymphoma after two or more lines of systemic therapy

Approved in European Union as Tepkinly for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
• Relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Findings from Research

Richter transformation (RT) occurs in 2-10% of chronic lymphocytic leukemia (CLL) patients and is often associated with a poor prognosis, particularly following therapy, with significant molecular changes such as TP53 inactivation in 50-60% of cases.

Despite the understanding of RT's molecular pathogenesis, patient outcomes have not significantly improved; however, there are now numerous clinical trials exploring new drugs and combinations specifically for RT, addressing a critical unmet need.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Richter Transformation in Chronic Lymphocytic Leukemia: Update in the Era of Novel Agents. Tadmor, T., Levy, I.[2021]

Richter transformation (RT) is a serious complication of chronic lymphocytic leukemia (CLL) that significantly worsens survival rates, with overall survival dropping to just 3-4 months for patients who have progressed on BTK or BCL2 inhibitors.

Novel therapeutic agents targeting BTK, BCL2, and the PD1-PDL1 axis show promise in potentially improving outcomes for patients with RT, highlighting the need for randomized clinical trials to better understand their efficacy and identify which patients may benefit most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Richter transformation-is there light at the end of this tunnel? Eyre, TA.[2023]

Richter syndrome (RS), a high-grade transformation of chronic lymphocytic leukaemia, is a chemotherapy-resistant condition with a poor prognosis, showing a median overall survival of only about 8 months, particularly affecting elderly and immunosuppressed patients.

Emerging treatments, including second-generation Bruton tyrosine kinase inhibitors like acalabrutinib and novel monoclonal antibodies, may offer new hope for improving outcomes in RS, highlighting the need for ongoing clinical trials and precision medicine approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update for Richter syndrome - new directions and developments. Eyre, TA., Schuh, A.[2022]

In a phase 2 study involving 9 patients with Richter's Syndrome, high-dose blinatumomab treatment led to a reduction in nodal disease in 4 patients, including one who achieved a durable complete response lasting over a year.

The treatment was well tolerated with no severe cytokine release syndrome and only one case of reversible grade 3 neurotoxicity, suggesting it is a safe option for patients with this aggressive form of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase two study of high dose blinatumomab in Richter's syndrome. Thompson, PA., Jiang, X., Banerjee, P., et al.[2023]

Richter syndrome (RS) occurs in 0.5-1% of chronic lymphocytic leukemia (CLL) patients per year and is often linked to a poor prognosis, with 80% of cases being clonally related to the prior CLL.

Current treatments for RS, including modern immunochemotherapy, show low response rates, but promising strategies such as stem-cell transplantation and novel immunotherapies are being explored to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Richter Syndrome: Diagnostic and Therapeutic Management]. Croizier, C., Guièze, R.[2021]

Richter transformation (RT) is a serious complication of chronic lymphocytic leukemia (CLL) that leads to aggressive lymphoma and is diagnosed through clinical findings and confirmed by tissue biopsy.

Current treatment for RT primarily involves chemoimmunotherapy, with ongoing research into newer therapies like CAR-T cell therapy and bispecific antibodies, which may improve outcomes for patients in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Richter Transformation of Chronic Lymphocytic Leukemia-Are We Making Progress? Audil, HY., Kosydar, SR., Larson, DP., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Richter Transformation in Chronic Lymphocytic Leukemia: Update in the Era of Novel Agents. [2021]

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

Richter transformation-is there light at the end of this tunnel? [2023]

3. England pubmed.ncbi.nlm.nih.gov

An update for Richter syndrome - new directions and developments. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A phase two study of high dose blinatumomab in Richter's syndrome. [2023]

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

[Richter Syndrome: Diagnostic and Therapeutic Management]. [2021]

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

Richter Transformation of Chronic Lymphocytic Leukemia-Are We Making Progress? [2023]