Epcoritamab + Tazemetostat for Follicular Lymphoma

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inducers/inhibitors

Disqualifiers: Active cardiovascular disease, CNS involvement, 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

Compensation: Varies

Number of Visits: 4

Duration: Up to 13 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of two treatments, epcoritamab and tazemetostat, for individuals with follicular lymphoma that has returned or not responded to previous treatments. Epcoritamab helps the immune system target and attack cancer cells, while tazemetostat stops cancer cells from growing. The trial seeks individuals diagnosed with follicular lymphoma grades 1-3A who have experienced a relapse or had no response to at least one prior lymphoma treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain medications like strong and moderate CYP3A4 inducers or inhibitors within 14 days before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that epcoritamab is effective in patients with relapsed or refractory follicular lymphoma. Most patients can manage its side effects, indicating a tolerable safety profile. The FDA has already approved tazemetostat for another condition, establishing its known safety record. Researchers believe combining these two treatments could effectively and safely treat this type of lymphoma. The current study is in phase 2, focusing on the treatment's safety in a larger group. Researchers continue to gather information on how well patients tolerate the combination of epcoritamab and tazemetostat. However, existing data for each treatment individually is promising. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about epcoritamab and tazemetostat for follicular lymphoma because they bring fresh approaches to tackling this condition. Unlike conventional treatments such as rituximab or chemotherapy, epcoritamab is a bispecific antibody that engages the immune system directly by targeting both CD3 on T-cells and CD20 on B-cells, potentially enhancing the body's natural ability to fight cancer. Tazemetostat is a novel EZH2 inhibitor, which can disrupt cancer cell growth by targeting an enzyme that plays a critical role in gene expression. This unique combination could provide a more effective option with potentially fewer side effects, offering hope for improved patient outcomes.

What evidence suggests that epcoritamab and tazemetostat might be effective for follicular lymphoma?

This trial will evaluate the combination of epcoritamab and tazemetostat for treating follicular lymphoma. Studies have shown that epcoritamab can help patients with relapsed or refractory follicular lymphoma, with some even reaching complete remission. Epcoritamab aids the immune system in identifying and attacking cancer cells. Tazemetostat, in contrast, stops cancer cells from growing by blocking certain necessary enzymes. Early research suggests that using these two drugs together may be more effective. Specifically, patients have experienced long-lasting remissions, indicating the treatment has kept cancer away for a longer time. Overall, the combination of epcoritamab and tazemetostat shows promise for treating follicular lymphoma. ^{1 2 3 6 7}

Who Is on the Research Team?

Swetha Kambhampati, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with grade I-IIIa follicular lymphoma that has either returned after treatment or hasn't responded to past treatments. Specific eligibility details are not provided, but typically participants must meet certain health standards and have a confirmed diagnosis.

Inclusion Criteria

Documented informed consent of the participant and/or legally authorized representative

My lymphoma has returned or didn't respond after my first treatment.

Total bilirubin ≤ 2 x upper limit of normal (ULN) (unless has Gilbert's disease or secondary to disease)

Exclusion Criteria

Concurrent enrollment in another therapeutic investigational study

I have not taken bispecific antibodies or tazemetostat before.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tazemetostat orally twice daily and epcoritamab subcutaneously on specified days of each cycle. Cycles repeat every 28 days for up to 13 cycles.

Up to 13 months

4 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits at 30 and 60 days, then for up to 2 years.

Up to 2 years

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab
• Tazemetostat

Trial Overview

The trial is testing the combination of epcoritamab, a bispecific antibody targeting cancer cell antigens, and tazemetostat, an enzyme inhibitor aimed at stopping cancer growth. This phase II study evaluates their safety and effectiveness in treating relapsed or refractory lymphoma.

How Is the Trial Designed?

Group I: Treatment (epcoritamab, tazemetostat) Experimental Treatment 6 Interventions

Patients receive tazemetostat PO BID on days 1-28 of each cycle. Patients also receive epcoritamab SC on days 1, 8, 15, and 22 of cycles 2-4 then on day 1 of remaining cycles. Cycles repeat every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples on study and undergo bone marrow biopsy and CT or PET/CT throughout the study.

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?

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

Three new third-generation aromatase inhibitors (anastrozole, letrozole, and vorozole) have shown superior efficacy and tolerability compared to previous treatments for post-menopausal women with metastatic breast cancer after tamoxifen therapy, based on phase III trials.

Letrozole is significantly more effective than megestrol acetate, while all three inhibitors are better tolerated than progestin treatments, particularly regarding weight gain, marking a clear advancement in second-line hormonal therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The third-generation non-steroidal aromatase inhibitors: a review of their clinical benefits in the second-line hormonal treatment of advanced breast cancer. Hamilton, A., Piccart, M.[2020]

Third-generation aromatase inhibitors (like anastrozole, letrozole, and exemestane) are effective first-line treatments for postmenopausal breast cancer patients, showing comparable efficacy and safety to the traditional treatment, tamoxifen.

Recent randomized clinical trials indicate that these aromatase inhibitors are well-tolerated and may offer advantages over tamoxifen, with ongoing studies exploring their use in both adjuvant settings and potentially in premenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in aromatase inhibitor therapy for breast cancer. Assikis, VJ., Buzdar, A.[2019]

In a study of 30 postmenopausal women with metastatic breast cancer, the sequential treatment of nonsteroidal aromatase inhibitors (Anastrozole and Letrozole) followed by Exemestane resulted in a significant clinical benefit, with 46.6% of patients showing improvement.

The findings suggest that there is a partial lack of cross-resistance between the different classes of aromatase inhibitors, indicating that switching from n-SAI to Exemestane can be an effective strategy for managing treatment in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of the use of exemestane as further hormonal therapy after nonsteroidal aromatase inhibitors in postmenopausal metastatic breast cancer patients. Carlini, P., Michelotti, A., Ferretti, G., et al.[2018]

Anastrozole and letrozole have been shown to be equivalent or superior to tamoxifen in treating women with metastatic breast cancer, based on large Phase III trials, indicating their effectiveness as first-line therapies.

In the adjuvant setting, early results from the ATAC trial suggest that anastrozole may provide a small but statistically significant improvement in disease-free survival compared to tamoxifen, although more follow-up is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical differences among the aromatase inhibitors. Ligibel, JA., Winer, EP.[2007]

The proposed phase III trial will evaluate the efficacy of letrozole as a maintenance therapy in 540 patients with newly diagnosed advanced epithelial ovarian cancer, aiming to improve progression-free survival (PFS) while minimizing toxicity and enhancing quality of life.

Letrozole, a potent aromatase inhibitor previously used in breast cancer treatment, is expected to show significant benefits in EOC patients, with a projected median PFS of 25.7 months compared to 18 months for the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance Therapy with Aromatase Inhibitor in epithelial Ovarian Cancer (MATAO): study protocol of a randomized double-blinded placebo-controlled multi-center phase III Trial. McLaughlin, PMJ., Klar, M., Zwimpfer, TA., et al.[2022]

Citations

1.

tandfonline.com

tandfonline.com/doi/full/10.1080/14737140.2025.2492787

An evaluation of epcoritamab as a treatment for relapsed or ...

In this paper we will review the efficacy and safety profile of the bispecific antibody epcoritamab in RR FL, either as monotherapy (as it was recently ...

2.

everyone.org

everyone.org/explore/compare?id1=340&id2=556

Tazverik (tazemetostat) vs Epkinly (epcoritamab-bysp)

Preliminary data suggest that Epkinly can induce responses in a significant number of patients, with some achieving complete remission. However, as an ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S2352302624001662

Epcoritamab monotherapy in patients with relapsed or ...

Epcoritamab monotherapy showed clinically meaningful activity in patients with multiply relapsed or refractory follicular lymphoma, and had a manageable safety ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12081106/

Follicular lymphoma: contemporary clinical management with ...

This review summarizes therapeutic approaches for FL, with a focus on therapies currently in development.

5.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1111/bjh.70126

Towards a chemo‐free approach for follicular lymphoma

These robust efficacy outcomes are accompanied by durable remissions, with a median DOR of 22.6 months and a median PFS of 20.7 months. CRS risk ...

6.

ashpublications.org

ashpublications.org/blood/article/146/15/1782/546730/Treatment-of-relapsed-and-refractory-follicular

Treatment of relapsed and refractory follicular lymphoma

Real-world data indicate retreatment with standard chemoimmunotherapy in patients with POD24 has limited success, supporting consideration of ...

7.

cancernetwork.com

cancernetwork.com/view/fda-approval-alert-epcoritamab-in-relapsed-refractory-follicular-lymphoma

FDA Approval Alert: Epcoritamab in Relapsed/Refractory ...

The FDA granted accelerated approval to epcoritamab-bysp (Epkinly) for patients with relapsed/refractory follicular lymphoma after 2 prior lines of therapy.