BI-1206 + Rituximab for Non-Hodgkin's Lymphoma

Recruiting at 27 trial locations

Overseen By Erika Bågeman

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioInvent International AB

Must not be taking: Corticosteroids, BTK inhibitors

Disqualifiers: Transplant, CNS compromise, Autoimmune, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for individuals with certain types of slow-growing B-cell non-Hodgkin's lymphoma that have recurred or not responded to standard treatments. The focus is on testing the experimental medication BI-1206 with Rituximab, and sometimes adding Acalabrutinib, to evaluate its effectiveness and safety. The trial includes different groups to test various doses and combinations. Individuals with B-cell non-Hodgkin's lymphoma who have previously received Rituximab might be suitable candidates for this study. As a Phase 1, Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot have had chemotherapy, small molecule products, radiotherapy, or immunotherapy within certain time frames before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research shows that BI-1206, when combined with rituximab, is generally well-tolerated by patients. Earlier studies reported manageable side effects. These studies showed promising results, indicating the treatment works well without causing serious issues.

For the under-the-skin version of BI-1206, research also found it safe and well-tolerated. Early results from these studies suggest the treatment has potential, even for patients with hard-to-treat conditions.

Overall, the treatment has been tested in various situations, and the safety data so far is encouraging. However, since the trial remains in the early stages, ongoing studies are crucial to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI-1206 combined with Rituximab for treating Non-Hodgkin's Lymphoma because it introduces a novel mechanism of action. Unlike standard treatments that typically target cancer cells directly, BI-1206 works by inhibiting a protein called FcγRIIB, which can down-regulate the effectiveness of antibody therapies like Rituximab. This unique approach potentially enhances the cancer-fighting power of Rituximab, making the combination more effective. Additionally, the trial is exploring different delivery methods for BI-1206, including both intravenous (IV) and subcutaneous (SC) routes, which may offer more flexibility and convenience for patients. The combination with Acalabrutinib in certain arms also adds a promising angle by targeting additional pathways involved in lymphoma progression.

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

Research has shown that combining BI-1206 with rituximab holds promise for treating non-Hodgkin's lymphoma. In earlier studies, all patients had their disease under control at their first check-up. The treatment proved effective for 63% of patients, indicating many responded positively. Early results also suggest that patients tolerate this combination well. In this trial, some participants will receive only BI-1206 and rituximab, while others will also receive acalabrutinib. Adding acalabrutinib, another cancer drug, in some parts of the trial may enhance the treatment's effectiveness. Overall, these findings suggest this treatment approach has strong potential. ^{3 6 7 8 9}

Who Is on the Research Team?

Mats Jerkeman, MD PhD

Principal Investigator

Senior Consultant and Adjunct Professor, Skane Univ Hospital, Lund, Sweden

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain types of B-cell Non-Hodgkin Lymphoma that's come back or didn't respond to treatment, including a rituximab-based one. They should be able to live at least another 12 weeks, have measurable disease, and be in fair health (ECOG 0-2). Pregnant women, those with severe heart issues, active infections needing treatment, other cancers or autoimmune diseases can't join.

Inclusion Criteria

I have lymph nodes that can be measured for cancer.

I am willing to have biopsies of my lymph nodes or other affected tissues.

I have been treated with a rituximab-based therapy before.

Exclusion Criteria

I have other types of cancer besides the one being studied.

My lymphoma has spread to the covering of my brain or spinal cord.

I need more than 10 mg of prednisolone daily, not just as pre-medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Dose escalation with two different arms assessing IV or SC dosing of BI-1206 in combination with rituximab

4 weeks

Weekly visits for dose administration

Phase 2a: Dose Expansion

Expansion cohort evaluating the selected IV dose of BI-1206 in combination with rituximab

28 days

Weekly visits for dose administration

Phase 2a: Signal Seeking

Assessing IV and SC dosing of BI-1206 in combination with rituximab and acalabrutinib, including a Safety Run-in and an Expansion

28 days

Weekly visits for dose administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• BI-1206

Trial Overview

The study tests BI-1206 combined with Rituximab in patients whose indolent B-cell Non-Hodgkin Lymphoma has relapsed or is resistant to Rituximab. It's a phase 1/2a trial aiming to see how safe the combination is and how well it works against this type of lymphoma.

How Is the Trial Designed?

Group I: Phase 2a SC Signal seeking Experimental Treatment 3 Interventions

SC Arm, BI-1206 in Combination with Rituximab and Acalabrutinib

Group II: Phase 2a IV Signal Seeking Experimental Treatment 3 Interventions

IV Arm, BI-1206 in Combination with Rituximab and Acalabrutinib

Group III: Phase 2a IV Dose expansion Experimental Treatment 2 Interventions

BI-1206 IV in Combination with Rituximab

Group IV: BI-1206 SC Dose Escalation Experimental Treatment 2 Interventions

Adaptive Dose Escalation of BI-1206 SC (Bayesian logistic regression model (BLRM) in combination with Rituximab

Group V: BI-1206 IV Dose Escalation Experimental Treatment 2 Interventions

Standard 3+3 Dose-Escalation of BI-1206 IV in combination with Rituximab

BI-1206 is already approved in United States, China, European Union for the following indications:

Approved in United States as BI-1206 for:

• Orphan designation for Follicular lymphoma and Mantle-cell lymphoma

Approved in China as BI-1206 for:

• Under clinical trial for Indolent B-Cell Non-Hodgkin Lymphoma

Approved in European Union as BI-1206 for:

• Under clinical trial for Indolent B-Cell Non-Hodgkin Lymphoma

Who Is Running the Clinical Trial?

BioInvent International AB

Lead Sponsor

Trials

19

Recruited

2,000+

Published Research Related to This Trial

In a retrospective study of 29 patients with various autoimmune diseases, rituximab demonstrated significant short-term efficacy, with most patients showing remarkable improvement except for one case of thrombocytopenic purpura.

The treatment was well tolerated, with no unexpected adverse events reported, and it led to a notable reduction in the need for steroid medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in refractory autoimmune diseases: Brazilian experience with 29 patients (2002-2004). Scheinberg, M., Hamerschlak, N., Kutner, JM., et al.[2017]

Rituximab, the first monoclonal antibody approved for cancer treatment, has been administered to approximately 36,000 patients, showing efficacy in treating relapsed or refractory CD20+ low-grade non-Hodgkin's lymphoma.

Serious infusion-related reactions, including cardiopulmonary issues and tumor lysis syndrome, occur in a small percentage of patients (0.04% to 0.07%), with higher risks in those with many circulating malignant cells or pre-existing cardiovascular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of rituximab for treatment of B-cell non-Hodgkin's lymphoma: a benefit-risk update. Kunkel, L., Wong, A., Maneatis, T., et al.[2022]

Rituximab is the first FDA-approved monoclonal antibody for cancer treatment, specifically targeting the CD20 antigen on B cells, and has shown efficacy in treating relapsed low-grade and follicular non-Hodgkin's lymphoma in multicenter studies.

The treatment is generally well-tolerated, with side effects mainly consisting of mild fevers and chills during the first infusion, and its low immunogenicity allows for potential future treatments without significant complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of rituximab, the new FDA-approved antibody. Leget, GA., Czuczman, MS.[2019]

In a phase II trial involving 58 patients with relapsed low-grade or follicular non-Hodgkin's lymphoma, re-treatment with rituximab showed a 40% overall response rate, with 11% achieving a complete response and 30% a partial response.

The safety profile was favorable, with most adverse events being mild and transient, and no significant myelosuppression observed, indicating that rituximab can be safely re-administered without major complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin's lymphoma: safety and efficacy of re-treatment. Davis, TA., Grillo-López, AJ., White, CA., et al.[2022]

In a phase II trial involving 39 patients with previously untreated low-grade non-Hodgkin lymphoma, rituximab demonstrated a high response rate of 54% after 6 weeks, with an overall response rate increasing to 64% after additional treatments.

Rituximab was well tolerated, with minimal toxicity reported; only one patient experienced significant infusion-related side effects, highlighting its potential as a safer treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab monoclonal antibody as initial systemic therapy for patients with low-grade non-Hodgkin lymphoma. Hainsworth, JD., Burris, HA., Morrissey, LH., et al.[2021]

Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown to induce responses in nearly 50% of patients with relapsed follicular/low-grade non-Hodgkin's lymphoma, with complete remissions occurring in 6% of cases, highlighting its efficacy in treating this type of cancer.

The drug is generally well tolerated, with common side effects being mild to moderate fevers and chills, and it is also effective against various other B-cell malignancies, suggesting its potential for broader applications in both cancer treatment and autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. Cheson, BD.[2019]

Rituximab has demonstrated a significant survival advantage in patients with diffuse large B-cell non-Hodgkin's lymphoma when used in combination with CHOP chemotherapy, marking the first improvement in over 20 years.

Emerging evidence suggests that earlier administration of rituximab and its use in maintenance therapy can enhance response rates and prolong remission, indicating its potential for optimizing treatment strategies in various B-cell disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of rituximab in haematological malignancies. Avivi, I., Robinson, S., Goldstone, A.[2023]

Rituximab is the first monoclonal antibody approved for treating B-cell lymphomas, showing significant effectiveness in conditions like follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma.

The combination of rituximab with standard chemotherapy agents (cyclophosphamide, doxorubicin, vincristine, and prednisone) has achieved the highest efficacy reported for treating diffuse large B-cell lymphoma and follicular lymphoma, while maintaining low toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. Traullé, C., Coiffier, BB.[2015]

The phase IIIb MAXIMA study involving 545 patients with follicular lymphoma demonstrated that rituximab maintenance therapy is safe, with most adverse events being mild (grade 1 or 2) and manageable, including low rates of serious infections.

Efficacy results for rituximab maintenance were consistent with previous trials, indicating it effectively prolongs time to progressive disease in patients who responded to initial rituximab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance with rituximab is safe and not associated with severe or uncommon infections in patients with follicular lymphoma: results from the phase IIIb MAXIMA study. Witzens-Harig, M., Foá, R., Di Rocco, A., et al.[2015]

In the SMARTE-R-CHOP-14 trial, elderly patients with diffuse large B-cell lymphoma (DLBCL) showed an 85% complete response rate and improved 3-year event-free survival (71%) and overall survival (84%) with prolonged rituximab exposure compared to historical controls.

Extended rituximab exposure did not increase toxicity and provided better outcomes for poor-prognosis patients compared to a standard treatment regimen, suggesting that this approach could be more effective for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the german high-grade non-Hodgkin lymphoma study group. Pfreundschuh, M., Poeschel, V., Zeynalova, S., et al.[2015]

The chimeric anti-CD20 monoclonal antibody IBI301 was well tolerated in nine Chinese patients with CD20(+) B-cell non-Hodgkin's lymphoma, with no severe adverse events or dose-limiting toxicities reported during the study.

IBI301 effectively eliminated peripheral CD20-expressing B cells in all patients, indicating its potential efficacy in targeting B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tolerance and pharmacodynamics phase Ⅰ clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin's lymphoma]. Jiang, B., Qi, JY., Sun, MY., et al.[2020]

Rituximab (RTX) is a widely used monoclonal antibody for treating diffuse large B-cell lymphoma, often combined with other drugs in the R-CHOP regimen, but some patients experience suboptimal responses or resistance.

New developments in CD20-targeting monoclonal antibodies, including second- and third-generation agents like ofatumumab and obinutumumab, are being actively researched to improve treatment outcomes for B-cell non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. Cang, S., Mukhi, N., Wang, K., et al.[2022]

In a study of 18 elderly patients with non-Hodgkin's lymphoma, the combination of rituximab and CHOP showed a high response rate of 91%, indicating its potential effectiveness as a treatment option.

While the overall survival and disease-free survival rates were slightly better in the rituximab plus CHOP group (91%) compared to CHOP alone (83% overall survival), the differences were not statistically significant, suggesting that further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of rituximab in combination with conventional chemotherapy for the treatment of non-Hodgkin's lymphoma of the head and neck. Manolopoulos, L., Gomatos, IP., Leandros, E., et al.[2015]

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