CC-99282 + Anti-Lymphoma Agents for Non-Hodgkin's Lymphoma

Recruiting at 128 trial locations

Overseen By BMS Study Connect Contact Center http://www.bmsstudyconnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Celgene

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Life expectancy ≤ 2 months, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

438 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new drug, CC-99282, for patients with certain types of lymphoma who haven't responded to other treatments. Researchers are finding the safest dose and checking if it works better alone or with other drugs.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot have had any systemic anti-cancer treatment within 4 weeks or 5 half-lives before starting the trial. Also, you cannot be on chronic immunosuppressive therapy or corticosteroids.

Is the treatment CC-99282 + Anti-Lymphoma Agents generally safe for humans?

Tafasitamab, when used with lenalidomide, has been associated with some adverse events like infections, blood disorders, and gastrointestinal issues, but it was generally well tolerated in patients with diffuse large B-cell lymphoma. Epcoritamab, another component, showed common side effects such as fatigue, nausea, and diarrhea, but was also generally well tolerated in patients with relapsed or refractory large B-cell lymphoma. ^{1 2 3 4 5}

What makes the drug CC-99282 + Tafasitamab unique for treating non-Hodgkin's lymphoma?

This drug combination is unique because it includes epcoritamab, a bispecific antibody that engages T-cells to target and kill cancerous B-cells, offering a novel approach for patients with relapsed or refractory non-Hodgkin's lymphoma, even those resistant to previous CD20 therapies. ^{1 6 7 8 9}

What data supports the effectiveness of the drug combination CC-99282 and other anti-lymphoma agents for treating non-Hodgkin's lymphoma?

Epcoritamab, a component of the treatment, has shown strong antitumor activity in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, and has received approval for treating diffuse large B-cell lymphoma (DLBCL) after multiple lines of therapy. Additionally, tafasitamab, another component, has demonstrated effectiveness in combination with lenalidomide for relapsed or refractory DLBCL, leading to its approval for patients ineligible for stem cell transplantation. ^{1 4 5 7 10}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for people with Non-Hodgkin's Lymphoma that has come back or hasn't responded to treatment. Participants should be fairly active and able to care for themselves (ECOG status 0-2). They can't join if they're on long-term immune-weakening drugs, have serious heart issues, are expected to live less than 2 months, or recently had cancer treatments.

Inclusion Criteria

My Non-Hodgkin's Lymphoma has come back or didn't respond to treatment.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I have heart problems that affect my daily activities.

There are other requirements that you must meet or avoid to participate in the study.

I am on long-term immunosuppressants or have significant GVHD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Evaluation of the safety and tolerability of escalating doses of CC-99282 to determine the maximum tolerated dose (MTD) as monotherapy

Variable duration

Dose Expansion

Further evaluation of the safety and preliminary efficacy of CC-99282 alone or in combination with anti-lymphoma agents

Variable duration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 6 years

What Are the Treatments Tested in This Trial?

Interventions

• CC-99282
• Obinutuzumab
• Rituximab
• Tafasitamab
• Tazemetostat

Trial Overview The study is testing the safety and initial effectiveness of a new drug called CC-99282 alone and combined with other lymphoma medications like Valemetostat, Tafasitamab, Obinutuzumab, and Rituximab in those whose lymphoma has relapsed or isn’t responding to current treatments.

How Is the Trial Designed?

Group I: Part B: Dose Expansion Experimental Treatment 5 Interventions

Group II: Part A: Dose Escalation Experimental Treatment 1 Intervention

CC-99282 is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Epkinly for:

• Diffuse large B-cell lymphoma
• High-grade B-cell lymphoma
• Follicular lymphoma

Approved in European Union as Tepkinly for:

• Diffuse large B-cell lymphoma
• High-grade B-cell lymphoma
• Follicular lymphoma

Approved in Canada as Epkinly/Tepkinly for:

• Diffuse large B-cell lymphoma

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

Tafasitamab, an anti-CD19 monoclonal antibody, received accelerated approval in July 2020 for treating adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in combination with lenalidomide, marking it as the first second-line therapy approved for this patient group in the USA.

The drug is administered intravenously at a recommended dose of 12 mg per kg and is also being explored for use in other B-cell malignancies, indicating its potential versatility in treating various types of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab: First Approval. Hoy, SM.[2022]

Epcoritamab, a bispecific antibody targeting CD3 and CD20, was found to be safe and well-tolerated in 73 patients with relapsed or refractory B-cell non-Hodgkin lymphoma, with no dose-limiting toxic effects and a recommended phase 2 dose established at 48 mg.

The treatment showed promising efficacy, with an overall response rate of 68% in patients with diffuse large B-cell lymphoma and 90% in those with follicular lymphoma, indicating its potential as a viable therapy for these difficult-to-treat conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Hutchings, M., Mous, R., Clausen, MR., et al.[2021]

In a study comparing tafasitamab combined with lenalidomide to lenalidomide alone in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), the combination therapy showed a significantly higher overall response rate of 67.1% compared to 34.2% for lenalidomide monotherapy.

The combination therapy also resulted in a higher complete response rate of 39.5% versus 13.2% for lenalidomide alone, indicating that tafasitamab enhances the efficacy of lenalidomide in treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a Real-world Lenalidomide Monotherapy Cohort in Relapsed or Refractory Diffuse Large B-cell Lymphoma. Zinzani, PL., Rodgers, T., Marino, D., et al.[2023]

Epcoritamab, a bispecific antibody targeting CD3 and CD20, showed a 63.1% overall response rate in 157 patients with relapsed or refractory large B-cell lymphoma, indicating its efficacy in this challenging patient population.

The treatment was generally well-tolerated, with manageable side effects; however, cytokine release syndrome was common (49.7%), and there was one reported fatality due to immune effector cell-associated neurotoxicity syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. Thieblemont, C., Phillips, T., Ghesquieres, H., et al.[2023]

Epcoritamab is a bispecific antibody that targets CD3 and CD20, designed for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), and received conditional approval in the USA on May 19, 2023, for adult patients after at least two prior therapies.

The drug has also received a positive opinion in the EU and is under review in Japan, indicating its potential as a significant treatment option for patients with difficult-to-treat B-cell non-Hodgkin lymphoma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epcoritamab: First Approval. Frampton, JE.[2023]

In a phase II study involving 61 patients with relapsed or refractory diffuse large B-cell lymphoma, coltuximab ravtansine showed an overall response rate of 43.9%, indicating moderate efficacy in this difficult-to-treat population.

The treatment was generally well tolerated, with common side effects including fatigue (30%) and nausea (23%), and serious adverse events were relatively low, suggesting a favorable safety profile for this antibody drug conjugate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy. Trnĕný, M., Verhoef, G., Dyer, MJ., et al.[2019]

Tafasitamab, a monoclonal antibody targeting CD19, showed a significant objective response rate of 56.8% in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) during the L-MIND clinical trial, with a median duration of response of 34.6 months.

The treatment was associated with notable adverse events, particularly infections (72.8% of patients) and blood disorders (65.4%), indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Tafasitamab in Combination With Lenalidomide for the Treatment of Adult Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma. Delgado, J., Papadouli, I., Sarac, SB., et al.[2021]

Rituximab was the first successful immunotherapy for B-cell non-Hodgkin lymphoma, marking a significant advancement in cancer treatment.

The review highlights the evolution of immunotherapeutic agents, including monoclonal antibodies and cellular therapies, which are now being developed to target various lymphoma subtypes, showing promise for treating non-Hodgkin lymphoma in younger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapeutic approaches for the treatment of childhood, adolescent and young adult non-Hodgkin lymphoma. Barth, MJ., Chu, Y., Hanley, PJ., et al.[2018]

The bispecific antibody CD20-TCB is designed to enhance T-cell engagement, which could improve the effectiveness of immunotherapy in treating B-cell lymphoma, particularly in patients with relapsed or refractory non-Hodgkin lymphoma.

Preclinical models have shown promising activity for CD20-TCB, suggesting it may offer a new therapeutic option for patients who have not responded to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunity War: A Novel Therapy for Lymphoma Using T-cell Bispecific Antibodies. Prakash, A., Diefenbach, CS.[2019]

Epcoritamab, a bispecific antibody, showed strong efficacy in killing primary tumor cells from patients with newly diagnosed and relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL), achieving median lysis rates of 65% to 84% across different lymphoma types.

The effectiveness of epcoritamab was consistent regardless of prior treatments, including CD20 monoclonal antibodies, indicating its potential as a treatment option for patients who have become resistant to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment. van der Horst, HJ., de Jonge, AV., Hiemstra, IH., et al.[2021]

Citations

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

Tafasitamab: First Approval. [2022]

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

Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. [2021]

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

RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a Real-world Lenalidomide Monotherapy Cohort in Relapsed or Refractory Diffuse Large B-cell Lymphoma. [2023]

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

Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. [2023]

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

Epcoritamab: First Approval. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy. [2019]

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

The European Medicines Agency Review of Tafasitamab in Combination With Lenalidomide for the Treatment of Adult Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Immunotherapeutic approaches for the treatment of childhood, adolescent and young adult non-Hodgkin lymphoma. [2018]

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

Immunity War: A Novel Therapy for Lymphoma Using T-cell Bispecific Antibodies. [2019]

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

Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment. [2021]