Epcoritamab + Tazemetostat for Follicular Lymphoma

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Swetha Kambhampati, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inducers/inhibitors

Disqualifiers: Active cardiovascular disease, CNS involvement, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase II trial tests the safety, side effects and effectiveness of epcoritamab and tazemetostat in treating patients with grade I-IIIa follicular lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Epcoritamab is a bispecific monoclonal antibody that binds to two different antigens on the surface of cancer cells that may help the body's immune system attack the cancer and may interfere with the ability of the cancer cells to grow and spread. Tazemetostat, a EZH2 inhibitor, may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving epcoritamab and tazemetostat may be safe, tolerable and/or effective in treating patients with relapsed or refractory grade I-IIIa follicular lymphoma.

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.

What makes the drug combination of Epcoritamab and Tazemetostat unique for treating follicular lymphoma?

The combination of Epcoritamab and Tazemetostat is unique because it targets follicular lymphoma using two different mechanisms: Epcoritamab is a bispecific antibody that engages the immune system to attack cancer cells, while Tazemetostat inhibits EZH2, a protein that can promote cancer growth. This dual approach may offer a novel treatment option compared to existing therapies. ^{1 2 3 4 5}

Eligibility Criteria

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.

My platelet count is at least 50,000, even if I needed a transfusion.

Exclusion Criteria

Concurrent enrollment in another therapeutic investigational study

I have not taken bispecific antibodies or tazemetostat before.

I am not on immunosuppressive drugs, except for prednisolone or its equivalent up to 20 mg daily.

Trial Timeline

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)

Treatment Details

Interventions

• Epcoritamab (Monoclonal Antibodies)
• Tazemetostat (Epigenetic Modifier)

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

City of Hope Medical Center Duarte, CA

City of Hope at Irvine Lennar Irvine, CA

Who Is Running the Clinical Trial?

City of Hope Medical Center Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

1. England 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. [2022] A high percentage of epithelial ovarian cancers (EOC) express the estrogen receptor (ER), which is an ideal target for endocrine therapy. Letrozole is a proven, potent aromatase inhibitor, extensively tested and used in the treatment of ER positive breast cancer. In addition, it seems a potent drug for patients with heavily pre-treated OC as demonstrated in several distinctive settings. However, it has never been evaluated prospectively in a maintenance setting for ovarian cancer after standard of care. The here proposed trial aims to define a population of EOC patients, who would benefit from the effectiveness of the generic agent letrozole, with little expected toxicity and thus beneficial impact on overall quality of life (QoL).

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

Recent advances in aromatase inhibitor therapy for breast cancer. [2019] Third-generation aromatase inhibitors (anastrozole, letrozole, and exemestane) have emerged as an alternative first-line endocrine treatment for postmenopausal breast cancer patients with hormone-responsive disease. Their clinical efficacy, excellent tolerability, and safety profile compare favorably with that of tamoxifen, which has been the cornerstone of endocrine therapy for years. This review will discuss the findings of recently published randomized clinical trials comparing this new class of drugs with tamoxifen as first-line treatment for advanced disease. We will also present the design and rationale of ongoing trials looking into the use of third-generation aromatase inhibitors in the adjuvant setting and review data regarding their possible role in premenopausal women.

3. England 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. [2020] Three new aromatase inhibitors have recently completed phase III evaluation as treatment of metastatic breast cancer in post-menopausal women whose disease has progressed despite tamoxifen therapy: anastrozole (ARIMIDEX, Zeneca), letrozole (FEMARA, Novartis) and vorozole (RIVIZOR, Janssen). All belong to the third generation of non-steroidal aromatase inhibitors, and each is superior to previous generations in terms of potency and selectivity. The trials that have been performed compare each agent to megestrol acetate, and letrozole and vorozole to aminoglutethimide. Although the studies are not directly comparable due to differing study designs and patient populations, it has been demonstrated each of these drugs provides single agent, once-daily, oral palliation of hormone-responsive, post-menopausal metastatic breast cancer. Letrozole is clearly more effective than megestrol acetate, and anastrozole and vorozole are possibly so. All three are better tolerated than the progestin, particularly in terms of weight gain. Both letrozole and vorozole are significantly more effective, and better tolerated than aminoglutethimide. Overall, this most recent generation of aromatase inhibitors is a clear improvement on our current standard second-line therapies. In 1999, tamoxifen remains the first choice in the hormonal therapy of breast cancer. Following tamoxifen failure, the optimal second-line hormonal therapy remains undefined, but aminoglutethimide and megestrol acetate are no longer optimal therapy in this setting. The third-generation non-steroidal aromatase inhibitors must now be compared to each other, to the steroidal aromatase inhibitors, to the pure anti-oestrogens, and to tamoxifen.

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

Clinical differences among the aromatase inhibitors. [2007] In the United States, three third-generation aromatase inhibitors are available commercially: anastrozole, letrozole, and exemestane. Anastrozole and letrozole are nonsteroidal agents, whereas exemestane is a steroid. The three agents differ in terms of structure and metabolic products and in the degree to which they suppress aromatase activity. The clinical significance of these differences is unclear. All three of the agents have been found to be equivalent or superior to megesterol acetate as a second-line therapy for metastatic breast cancer. In the first-line setting, large Phase III trials have demonstrated that anastrozole and letrozole are equivalent or superior to tamoxifen in women with metastatic disease. Multiple trials with widely varying study designs have been launched in the adjuvant setting comparing the aromatase inhibitors to tamoxifen. Early results from the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial suggest a small but statistically significant improvement in disease-free survival for anastrozole compared with tamoxifen, but further follow-up is needed. This article explores the efficacy and tolerability of the aromatase inhibitors in both the metastatic and the adjuvant settings.

5. England 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. [2018] The aromatase inhibitors Anastrozole, Letrozole (type 2 nonsteroidal aromatase inhibitors: n-SAI) and Exemestane (type 1 steroidal aromatase inactivator) are used respectively as first- and second-line hormonal therapy in postmenopausal metastatic breast cancer women. Few clinical data are published on the sequential use of different classes of aromatase inhibitors.