Epcoritamab + Tazemetostat for Follicular Lymphoma

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

33 Participants Needed

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}

Research Team

Swetha Kambhampati, MD

Principal Investigator

City of Hope Medical Center

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.

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
• 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.

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

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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

Recent advances in aromatase inhibitor therapy for breast cancer. [2019]

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]

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

Clinical differences among the aromatase inhibitors. [2007]

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]