Glofitamab + Obinutuzumab for Non-Hodgkin's Lymphoma

Recruiting at 69 trial locations

Overseen By Reference Study ID Number: NP30179 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: Immunotherapeutics, Chemotherapy, Immunosuppressants, others

Disqualifiers: CLL, CNS disease, Cardiovascular, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

920 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with Non-Hodgkin's Lymphoma, a cancer affecting the lymphatic system. The study aims to determine the optimal dose of a new drug, glofitamab (COLUMVI), both alone and in combination with another drug, obinutuzumab, to evaluate their effectiveness and safety. Suitable candidates for this trial include those whose lymphoma has returned after treatment or has not responded to at least one previous therapy. Participants should have a noticeable tumor and no other current treatment options expected to extend their life. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received certain treatments like systemic immunotherapeutic agents or standard chemotherapy within 4 weeks before starting the trial. It's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications before starting the study. Specifically, you must not have taken systemic immunotherapeutic agents, standard chemotherapy, or other investigational anti-cancer agents within 4 weeks prior to the study. Additionally, you should not have received systemic immunosuppressive medications within two weeks before the study, except for low-dose corticosteroids.

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

Research has shown that glofitamab has generally been well-tolerated in past studies, though some serious side effects have occurred. A few patients reported infections, such as COVID-19 and sepsis, a severe infection that can spread throughout the body. More than half of the patients experienced some side effects, with many being serious.

When combined with obinutuzumab, glofitamab has been studied in other research. These studies remain in the early stages, so information on the safety of using these treatments together is limited. Ongoing research aims to understand how well people can tolerate this combination and what side effects might occur.

Since the current trial is in its early phases, it focuses on finding safe doses and understanding possible side effects. Safety information is still being collected and reviewed. Prospective participants should be aware of potential risks and discuss them with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about glofitamab and obinutuzumab for treating Non-Hodgkin's Lymphoma because they offer a novel approach compared to existing options like chemotherapy and standard monoclonal antibodies. Glofitamab is a bispecific antibody that uniquely targets both the CD20 protein on B-cells and the CD3 protein on T-cells, potentially enhancing the immune system's ability to attack cancer cells directly. Obinutuzumab, an anti-CD20 monoclonal antibody, is combined with glofitamab to boost this effect, possibly leading to improved outcomes. This dual-action strategy could offer a more targeted and potent treatment, sparking hope for better efficacy and fewer side effects.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma?

Research shows that glofitamab, a type of antibody treatment, has promising results for certain lymphoma patients. Studies found that glofitamab reduced cancer symptoms in 52% of patients with relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL), meaning more than half of these patients saw improvement. In this trial, some participants will receive glofitamab alone, while others will receive it with obinutuzumab, a drug targeting cancer cells. This combination aims to boost the immune system's ability to fight lymphoma. While the effectiveness of this combination is still under study, researchers believe it works better together in attacking cancer cells. ^{3 5 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with relapsed/refractory B-Cell Non-Hodgkin's Lymphoma who've had at least one prior treatment and lack other survival-prolonging options. Participants must have measurable disease, be in good physical condition (ECOG 0 or 1), and have proper liver, kidney, and blood function. Pregnant women are excluded, as well as those with certain infections or a history of severe reactions to similar drugs.

Inclusion Criteria

Negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential

I have no treatment options left that could extend my life.

I can provide a fresh biopsy from a site that is safe to access, as long as I have more than one measurable lesion.

Exclusion Criteria

I haven't taken any immune-weakening drugs in the last two weeks.

I haven't had cancer treatment in the last 4 weeks.

I don't have an ongoing infection confirmed by a test or doctor's opinion.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive obinutuzumab pretreatment followed by glofitamab IV infusion with ascending doses to determine MTD/OBD

24 weeks

Bi-weekly visits for 12 cycles

Dose Expansion

Participants receive glofitamab at a fixed or step-up dose regimen to further evaluate safety and therapeutic activity

12 cycles

Every 2 or 3 weeks as determined in Part II

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Glofitamab
• Obinutuzumab
• Tocilizumab

Trial Overview The study tests Glofitamab alone or combined with Obinutuzumab in patients pre-treated with a fixed dose of Obinutuzumab. It's an early-phase trial to find the safest and most effective doses (Phase I/II). The trial includes escalating doses followed by expansion cohorts once optimal dosing is determined.

How Is the Trial Designed?

Group I: Part III: Dose Expansion Experimental Treatment 3 Interventions

Part III will start once MTD/OBD is defined. Participants will receive Gpt 1000 mg single dose IV infusion on Day -7, followed by glofitamab at a fixed dose regimen or step-up dose regimen on a Q2W or Q3W dosing schedule as determined in Part II. A total of 12 cycles will be administered. Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with glofitamab at the dosing regimen determined in Part II.

Group II: Part II: Dose Escalation Experimental Treatment 3 Interventions

In each treatment regimen, participants will receive Gpt 1000 mg IV infusion on Day -7; or 2000 mg either administered on Day -7, or split into two 1000 mg doses on Days -1 and -7. The first glofitamab IV infusion will be given on Day 1 of Cycle 1 and a total of 12 cycles will be administered. Monotherapy, glofitamab as a single agent: ascending doses of glofitamab administered on Day 1 of Q2W or every 3 week (Q3W) cycle until either the MTD/OBD is defined. Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with ascending doses of glofitamab on Day 1 of Q3W cycle until either the MTD/OBD is defined. Step-up dosing: Q3W, participants will receive an initial low dose of glofitamab on Cycle 1 Day 1, followed by a higher dose on Cycle 1 Day 8; the total dose in Cycle 1 will not exceed the previously determined MTD. Higher doses may be explored from Cycle 2 or later cycles.

Group III: Part I: Dose Escalation Experimental Treatment 3 Interventions

Participants (single participant cohorts) will receive obinutuzumab pretreatment (Gpt) 1000 milligrams (mg) single dose IV infusion on Day -7 followed by glofitamab IV infusion on Day 1 and Day 8 of Cycle 1. From Cycle 2 onwards, ascending doses of glofitamab will be administered on Day 1 of every 2 week (Q2W) cycle up to Cycle 12 (24 weeks) or until unacceptable toxicity or disease progression. Glofitamab dosing will be initiated at 5 micrograms (mcg) (flat dose) followed by doses of 15 mcg, 45 mcg, 135 mcg, 405 mcg and 810 mcg.

Glofitamab is already approved in United States for the following indications:

Approved in United States as COLUMVI for:

• Relapsed or refractory diffuse large B-cell lymphoma not otherwise specified (DLBCL), or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

In a real-world study of 43 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) treated with glofitamab, the median overall survival was 8.8 months, indicating promising efficacy in a heavily pretreated population.

However, the study also highlighted significant safety concerns, with treatment-related deaths occurring due to cytokine release syndrome and febrile neutropenia, emphasizing the need for careful monitoring of hematological toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: Real-world data. Birtas Atesoglu, E., Gulbas, Z., Uzay, A., et al.[2023]

In a study of 143 treatment-naïve patients with follicular lymphoma, obinutuzumab-based induction regimens showed high effectiveness, with a complete response rate of 69.9% and a partial response rate of 26.5%.

Infusion-related reactions were infrequent, occurring in only 9.1% of patients during the first administration of obinutuzumab, regardless of whether the total dose was given in one day or split over two days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early efficacy and safety of obinutuzumab with chemotherapy in previously untreated patients with follicular lymphoma: A real-world retrospective report of the Polish Lymphoma Research Group. Paszkiewicz-Kozik, E., Hus, I., Palka, M., et al.[2023]

In a study of 56 patients with relapsed/refractory follicular lymphoma, obinutuzumab combined with chemotherapy (either G-CHOP or G-FC) resulted in high response rates of 93% to 96%, indicating strong efficacy for this treatment approach.

The safety profile was acceptable, with most adverse events being mild infusion-related reactions; however, G-FC was associated with more adverse events compared to G-CHOP, suggesting that while both regimens are effective, G-CHOP may be better tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). Radford, J., Davies, A., Cartron, G., et al.[2022]

In the GALLIUM trial involving patients with front-line follicular lymphoma, obinutuzumab (G) exposure was found to be lower in males and patients with higher body weight, but this variability did not affect progression-free survival (PFS) in those treated with G plus bendamustine.

For patients receiving G with CHOP or CVP chemotherapy, higher average drug concentration (CmeanIND) was associated with improved PFS, suggesting that drug exposure may play a role in treatment efficacy for these combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of obinutuzumab exposure on clinical outcome of follicular lymphoma treated with first-line immunochemotherapy. Jamois, C., Gibiansky, E., Gibiansky, L., et al.[2021]

Obinutuzumab, a novel anti-CD20 monoclonal antibody, shows improved efficacy over rituximab in treating patients with rituximab-relapsed/refractory follicular lymphoma, as demonstrated through an analysis of data from 6 clinical trials involving patients with CD20+ B-cell malignancies.

The pharmacokinetic model indicates that while higher exposure to obinutuzumab is associated with greater efficacy, particularly in terms of longer progression-free survival, the clinical benefits of the treatment are achieved regardless of exposure variability, ensuring safety and minimizing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study. Gibiansky, E., Gibiansky, L., Buchheit, V., et al.[2021]

Obinutuzumab (G) combined with chemotherapy (G + Chemo) is shown to be a cost-effective treatment for previously untreated follicular lymphoma (FL) in Japan, with incremental cost-effectiveness ratios (ICERs) below the acceptable threshold of 7.5 million JPY per quality-adjusted life year (QALY).

The study found that the lowest lifetime direct medical costs were associated with the R-bendamustine (R-B) treatment group, primarily due to reduced hospitalization costs, highlighting the impact of treatment settings on overall expenses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of treatment regimens with obinutuzumab plus chemotherapy in Japan for untreated follicular lymphoma patients. Ohno, S., Shoji, A., Hatake, K., et al.[2021]

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]

Glofitamab, a bispecific monoclonal antibody targeting CD20 and CD3, was conditionally approved in Canada on March 25, 2023, for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have undergone multiple prior therapies and are ineligible for CAR T-cell therapy.

The drug is currently under regulatory review in the EU and USA, with ongoing clinical development as both a standalone treatment and in combination with other therapies for non-Hodgkin lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab: First Approval. Shirley, M.[2023]

Glofitamab, a bispecific antibody, demonstrated a 53.8% overall response rate in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, with a complete response rate of 36.8%, indicating its efficacy in a heavily pretreated population.

The treatment had a manageable safety profile, with cytokine release syndrome occurring in 50.3% of patients but mostly at lower grades, and only 2.9% of patients withdrew due to adverse events, suggesting that glofitamab can be safely administered with prior obinutuzumab pretreatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. Hutchings, M., Morschhauser, F., Iacoboni, G., et al.[2023]

Glofitamab is a novel bispecific T-cell recruiting antibody that targets both CD20 on B-cells and CD3 on T-cells, showing over 50% complete response rates in heavily treated patients with aggressive and indolent B-cell lymphoma during Phase 1 trials.

The unique 2:1 configuration of glofitamab allows for an extended half-life and superior binding to CD20, making it a promising option for patients with limited treatment choices, with ongoing trials evaluating its efficacy in combination therapies and earlier treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab CD20-TCB bispecific antibody. Minson, A., Dickinson, M.[2022]

Glofitamab, a bispecific antibody targeting CD20 and CD3, demonstrated clinical activity in patients with relapsed/refractory B-cell non-Hodgkin lymphoma during a phase 1 trial, showing T-cell activation and tumor cell killing.

The study identified that tumor intrinsic factors, such as TP53 signaling, may contribute to resistance against glofitamab, indicating that these factors could serve as important biomarkers for predicting treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma. Bröske, AE., Korfi, K., Belousov, A., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/146/18/2177/546196/Real-world-outcomes-of-patients-with-aggressive-B

Real-world outcomes of patients with aggressive B-cell ... A total of 201 of 245 patients (82.0%) were efficacy-evaluable (124 treated with epcoritamab [80%], and 77 treated with glofitamab [87%]).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12334432/

Efficacy and safety of Glofitamab in patients with R/R ... Glofitamab, a CD20-directed CD3 T-cell engager, was recently FDA-approved after demonstrating a 52% overall response rate (ORR) and a 39% ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206913

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell ... Glofitamab therapy was effective for DLBCL. More than half the patients had an adverse event of grade 3 or 4.

4. oncologynewscentral.com oncologynewscentral.com/drugs/info/fda-rejects-glofitamab-for-diffuse-large-b-cell-lymphoma-indication

FDA Rejects Glofitamab for Diffuse Large B-cell Lymphoma ... Results from the trial showed a 41% reduction in the risk for death (hazard ratio, 0.59; 95% confidence interval, 0.40–0.89; P=.011) for ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924007195

Safety and efficacy of glofitamab for relapsed/refractory ... As detailed above, the median time to relapse was 60 days and 34 of 38 patients with PD/SD died at the last follow-up, with a median of 3 months ...

6. columvi-hcp.com columvi-hcp.com/safety/important-safety-information.html

COLUMVI™ (glofitamab-gxbm) Important Safety Information Grade 3 or higher infections reported in ≥ 2% patients were COVID-19 infection (6%), including COVID-19 pneumonia, and sepsis (4.1%). Febrile neutropenia ...

7. columvi.com columvi.com/

COLUMVI (glofitamab-gxbm) is for people with certain types of ... It is not known if COLUMVI is safe and effective in children. The conditional approval of COLUMVI is based on response rate and durability of response.

8. ashpublications.org ashpublications.org/blood/article/146/15/1824/546454/Preclinical-advances-in-glofitamab-combinations-a

Preclinical advances in glofitamab combinations: a new ... This study provides a comprehensive preclinical evaluation of glofitamab-based combinations in humanized lymphoma models and primary patient ...