Obinutuzumab + CC-99282 for Follicular Lymphoma

Overseen By Dai Chihara, M D, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A inhibitors, Corticosteroids

Disqualifiers: CNS lymphoma, HIV, Hepatitis, 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: Unknown

Duration: 24 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining obinutuzumab (Gazyva) and CC-99282 can effectively control follicular lymphoma, a type of blood cancer, particularly in untreated cases with a high tumor load. Participants will receive these treatments together over several cycles to assess their impact on the disease. The trial seeks individuals who have not received prior systemic treatment for their lymphoma and are experiencing symptoms like night sweats or significant, unexplained weight loss. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in lymphoma care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on strong CYP3A inhibitors, you must stop them and wait for a 7-day washout period (time without taking certain medications) or 5 half-lives, whichever is longer, before starting the trial.

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

Research shows that the combination of obinutuzumab and CC-99282 is under evaluation for safety in treating follicular lymphoma. Earlier studies found that CC-99282, when combined with other anti-lymphoma drugs, was generally safe and well-tolerated, with manageable side effects.

Obinutuzumab has already received approval for other uses, so doctors understand its effects on the body and the expected side effects.

This trial is in Phase 2, indicating that earlier research deemed the combination safe enough for further testing. However, participants might still experience some side effects, which researchers will closely monitor during the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for follicular lymphoma?

Unlike the standard treatments for follicular lymphoma, which often involve chemotherapy and rituximab, the combination of Obinutuzumab and CC-99282 works differently by targeting cancer cells more precisely. Obinutuzumab is an engineered antibody that binds to a specific protein on the surface of lymphoma cells, enhancing the immune system's ability to destroy them. CC-99282 is a novel compound that can potentially boost this immune response further, making it a unique one-two punch against the disease. Researchers are excited about these treatments because they offer a targeted approach that might be more effective and possibly have fewer side effects compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for follicular lymphoma?

Research has shown that obinutuzumab, when combined with CC-99282, may effectively treat follicular lymphoma. This trial will administer the combination to participants to assess its potential to completely eliminate the cancer after six treatment cycles. Obinutuzumab, tested with lenalidomide, demonstrated high success rates and delayed cancer progression. This indicates that obinutuzumab can work well with other treatments for follicular lymphoma. The combination with CC-99282 is under study to determine if it can achieve similar or even better results. Although this specific combination is still under investigation, previous success with obinutuzumab in similar treatments is promising. ^{1 6 7 8 9}

Who Is on the Research Team?

Dai Chihara, M D

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with previously untreated, high tumor burden follicular lymphoma. Participants must have certain blood count levels, no prior cancer treatments, and be in a specific disease stage. They should not be pregnant or breastfeeding and must agree to contraception measures.

Inclusion Criteria

My condition is at stage II, III, or IV.

I can take care of myself but might not be able to do heavy physical work.

I have a tumor larger than 7 cm outside of my spleen.

Exclusion Criteria

I have had cancer other than B-NHL but have been free of it for over 3 years.

I do not have any severe illnesses that could affect my safety or the study's results.

I do not have serious heart problems or recent heart attacks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive obinutuzumab and CC-99282 for up to 6 cycles, each cycle lasting 28 days

24 weeks

Extended Treatment

Participants may continue to receive obinutuzumab and CC-99282 for Cycles 7-12 based on disease status

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 months

What Are the Treatments Tested in This Trial?

Interventions

• CC-99282
• Obinutuzumab

Trial Overview The study tests the effectiveness of obinutuzumab combined with CC-99282 in controlling high tumor burden follicular lymphoma that hasn't been treated before. It's a Phase 2 trial focusing on these two drugs' impact on this type of lymphoma.

How Is the Trial Designed?

Group I: Obinutuzumab+CC-99282 Experimental Treatment 2 Interventions

Participants will receive obinutuzumab and CC-99282 together for up to 12 study cycles. Each study cycle is 28 days. Participants will first receive the study drugs for Cycles 1-6. Then after participants complete Cycle 6, the study doctor will decide based on the status of the disease if participant will continue to receive the study drugs for Cycles 7-12 or if participant will stop receiving them.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Obinutuzumab, a new anti-CD20 monoclonal antibody, has shown promising efficacy in treating follicular lymphoma (FL) and has been approved by the FDA for use in combination with bendamustine for patients who have relapsed after rituximab treatment.

Ongoing phase III trials, such as the GALLIUM trial, suggest that obinutuzumab may soon be established as a first-line treatment for FL, potentially replacing rituximab as the gold standard, although some safety concerns remain to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab in follicular lymphoma. Martinez-Calle, N., Figueroa-Mora, R., Villar-Fernandez, S., et al.[2017]

The Phase III GADOLIN trial showed that obinutuzumab combined with bendamustine significantly improves progression-free survival in patients with rituximab-refractory indolent non-Hodgkin lymphoma compared to bendamustine alone.

Obinutuzumab has received FDA approval for treating follicular lymphoma that has relapsed or is refractory to rituximab, highlighting its efficacy in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab for the treatment of indolent lymphoma. Edelmann, J., Gribben, JG.[2018]

Obinutuzumab (GA101) is an effective treatment for non-Hodgkin's lymphoma and is currently undergoing phase 3 clinical trials to further evaluate its efficacy.

A case report of a 62-year-old patient revealed a significant side effect, a widespread lichenoid eruption, highlighting the need for further investigation into the safety profile of GA101.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GA101 (a Novel Anti-CD20 Monoclonal Antibody)-Induced Lichenoid Eruption. Bakkour, W., Coulson, IH.[2022]

The study developed 64Cu-labeled F(ab')2 fragments of obinutuzumab, which showed rapid and sustained tumor uptake in CD20-positive lymphoma models, indicating potential for effective imaging of lymphoma.

With a radiochemical purity of over 98% and significantly higher tumor uptake compared to controls, this method could enhance noninvasive evaluation of CD20 levels in clinical settings, improving diagnosis and treatment monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Evaluation of CD20 Expression Using 64Cu-Labeled F(ab')2 Fragments of Obinutuzumab in Lymphoma. Kang, L., Li, C., Rosenkrans, ZT., et al.[2021]

The combination of obinutuzumab and atezolizumab was found to be safe and tolerable in a phase 1b study involving 49 patients with relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), with no new toxicities reported.

The treatment showed preliminary efficacy, achieving a 54% objective response rate in the FL cohort and a 17% response rate in the DLBCL cohort, with median progression-free survival of 9 months for FL and 3 months for DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Atezolizumab and Obinutuzumab in Patients with Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-Cell Lymphoma: Results from a Phase 1b Study. Palomba, ML., Till, BG., Park, SI., et al.[2022]

Obinutuzumab, a novel CD20 antibody, demonstrated superior anti-tumor activity compared to rituximab in preclinical mouse models of non-Hodgkin lymphoma, particularly when combined with chemotherapy agents like bendamustine.

In these studies, obinutuzumab alone was at least as effective as rituximab combined with chemotherapy, suggesting it could be a more effective treatment option for patients with non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma. Herting, F., Friess, T., Bader, S., et al.[2021]

Obinutuzumab, combined with bendamustine, significantly prolonged progression-free survival (PFS) in patients with indolent non-Hodgkin's lymphoma, particularly benefiting those with follicular lymphoma, as shown in the phase III GADOLIN study.

The treatment was generally well-tolerated, with mild to moderate infusion-related reactions being the most common side effects, while neutropenia was the most frequent severe adverse event, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma. Dhillon, S.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06108232?intr=Obinutuzumab&aggFilters=status:rec%20act%20not&rank=9

Phase 2 Trial of Obinutuzumab and CC-99282 for Patients ... To determine the efficacy of obinutuzumab in combination with CC-99282 as determined by complete response (CR) rate after six cycles of combination treatment ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06510361?term=epcoritamab&viewType=Table&rank=9

Epcoritamab in Patients With Follicular Lymphoma Not ... This research is being done to see if epcoritamab is effective in treating follicular lymphoma as a second line of treatment. The name of the study drug in this ...

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

Follicular lymphoma: contemporary clinical management with ... Obinutuzumab was combined with lenalidomide in the phase II GALEN study, yielding an ORR of 92% and a 2-year PFS rate of 82% [105]. Overall, R2 is a therapeutic ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2473952925003143

Indirect comparison of epcoritamab vs ... Epcoritamab showed significantly superior response rates and survival outcomes vs SOC/CIT among patients with relapsed or refractory FL after ≥2 systemic ...

5. onclive.com onclive.com/view/chemotherapy-free-combos-lead-the-way-in-r-r-follicular-lymphoma

Chemotherapy-Free Combos Lead the Way in R/R ... Lenalidomide plus rituximab is a pivotal second-line therapy for relapsed/refractory follicular lymphoma, with ongoing trials exploring ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-09268

Obinutuzumab and CC-99282 for the Treatment of Patients ... Giving obinutuzumab and CC-99282 in combination may be effective at controlling disease in patients with previously untreated follicular lymphoma. Eligibility ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03930953

NCT03930953 | A Safety and Preliminary Efficacy Study of ... The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of CC-99282 alone and in combination with anti-lymphoma agents.

8. ashpublications.org ashpublications.org/blood/article-pdf/doi/10.1182/blood.2025029909/2411544/blood.2025029909.pdf

Fixed-Duration Epcoritamab Plus R2 Drives Favorable ... Mosunetuzumab in combination with lenalidomide has a manageable safety profile and encouraging activity in patients with relapsed/refractory follicular lymphoma ...

9. ir.genmab.com ir.genmab.com/news-releases/news-release-details/epkinlyr-epcoritamab-bysp-approved-us-fda-patients-relapsed-or

EPKINLY® (epcoritamab-bysp) Approved by U.S. FDA for ... Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study. Haematologica ...