AD-PluReceptor + Tafasitamab for Autoimmune Disorders

Overseen By Chitra Hosing, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Rituximab, Voclosporin, Anifrolumab, others

Disqualifiers: Pulmonary disease, Cardiac manifestations, CNS pathology, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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

Compensation: Varies

Number of Visits: Unknown

47 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for autoimmune disorders, specifically targeting systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and lupus nephritis (LN). The researchers aim to confirm the safety of the drug tafasitamab (Monjuvi) and determine the optimal dose of AD-PluReceptor-NK cells with other medications to manage these conditions. Participants who may be suitable for the trial are those who have struggled to control their SSc, SLE, or LN with current treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, it mentions that if you are on standard immunosuppressive therapy, it must have been started at least 12 weeks before screening and be stable for at least 8 weeks. Please consult with the trial team for specific guidance.

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

Research has shown that tafasitamab is already approved by the FDA to treat follicular lymphoma, indicating its safety for certain conditions. Previous studies demonstrated that tafasitamab, when combined with other treatments, can manage the disease without severe side effects.

However, the combination of AD-PluReceptor NK cells and tafasitamab is still under investigation to determine the safest dose for patients with autoimmune disorders like lupus. As this trial is in its early stages, researchers are still assessing how well patients tolerate this combination. Early trials focus on safety, so some unknowns may exist. Nevertheless, tafasitamab's use in other treatments supports its safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AD-PluReceptor combined with Tafasitamab-cxix for autoimmune disorders because it offers a novel approach compared to current treatments. Unlike traditional therapies that may broadly suppress the immune system, Tafasitamab-cxix specifically targets CD19, a protein found on B cells, which are often involved in autoimmune responses. This targeted action can potentially reduce side effects and improve effectiveness. Additionally, the combination with AD-PluReceptor might enhance the body's ability to regulate its immune response more precisely, offering hope for better disease management.

What evidence suggests that this trial's treatments could be effective for autoimmune disorders?

Research has shown that targeting molecules involved in autoimmune diseases, such as BAFF and APRIL, can be effective. Tafasitamab, a key component of this study, provided lasting benefits in previous research, particularly for certain cancers. Real-world data confirms that tafasitamab helps patients live longer without disease progression. Although approved for other conditions, this trial explores its potential to treat autoimmune disorders by combining it with AD-PluReceptor-NK cells and chemotherapy. Participants will receive different combinations of these treatments in various arms, and early results suggest this method could help manage the disease by targeting specific immune cells. ^{1 2 3 4 5}

Who Is on the Research Team?

Chitra Hosing, MD

Principal Investigator

MDAnderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with autoimmune diseases like systemic sclerosis or scleroderma. Participants should have a diagnosis of these conditions and be suitable for the treatments being tested, which include chemotherapy.

Inclusion Criteria

I am fully active or can carry out light work.

Positive ANA by immunofluorescence at titer ≥ 1:80

I have been diagnosed with systemic sclerosis according to the 2013 criteria.

Exclusion Criteria

History of severe reactions to specified treatments

My condition does not meet any specific exclusion criteria for SLE.

I have severe heart problems due to lupus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-In

Confirm the safety of tafasitamab when given to patients with SSc, SLE, and LN

4-6 weeks

Phase 1

Determine the recommended dose of AD-PluReceptor-NK cells in combination with tafasitamab and lymphodepleting chemotherapy

8-12 weeks

Phase 2

Evaluate if the dose of AD-PluReceptor-NK cells found in Phase 1 can help control the disease

16-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine phosphate
• Tafasitamab-cxix

Trial Overview The study is testing AD-PluReceptor-NK cells combined with tafasitamab and lymphodepleting chemotherapy. It aims to confirm safety, find the best dose, and see if this combination can control autoimmune disorders effectively.

How Is the Trial Designed?

Group I: Safety Lead-In Experimental Treatment 1 Intervention

Group II: Dose Expansion Experimental Treatment 4 Interventions

Group III: Dose Escalation Experimental Treatment 4 Interventions

Tafasitamab-cxix is already approved in United States for the following indications:

Approved in United States as Monjuvi for:

• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including those arising from low-grade lymphoma, in adult patients who are not eligible for autologous stem cell transplantation

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

BAFF and APRIL are important for maintaining B cells and are linked to autoimmune diseases, making them potential targets for new therapies; inhibitors like atacicept and belimumab are being tested in clinical trials.

Baseline levels of BAFF and APRIL in patients may predict how well they respond to treatments like belimumab and atacicept, highlighting the need for further research to refine these biomarkers for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases. Samy, E., Wax, S., Huard, B., et al.[2022]

Rozibafusp alfa, a bispecific antibody-peptide conjugate, was well tolerated in a phase 1b study with 34 patients suffering from rheumatoid arthritis, showing that most treatment-emergent adverse events were mild or moderate in severity.

The treatment demonstrated significant biological activity, with dose-related effects on immune cell populations and greater improvements in rheumatoid arthritis disease activity compared to placebo, particularly in higher dose cohorts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Biological Activity of Rozibafusp alfa, a Bispecific Inhibitor of Inducible Costimulator Ligand and B Cell Activating Factor, in Patients With Rheumatoid Arthritis: Results of a Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study. Abuqayyas, L., Cheng, LE., Teixeira Dos Santos, M., et al.[2022]

Rituximab, an anti-CD20 monoclonal antibody, showed an acceptable safety profile in a study of 10 pediatric patients with severe autoimmune diseases, although there were serious infections in three patients and one death related to underlying conditions.

The treatment led to significant clinical improvements in nine patients, allowing for a median reduction of 63% in corticosteroid use, with some patients achieving complete discontinuation of steroids, although not all maintained long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effects and safety of rituximab for treatment of refractory pediatric autoimmune diseases. El-Hallak, M., Binstadt, BA., Leichtner, AM., et al.[2019]

Rituximab, an anti-CD20 antibody, effectively treated three patients with severe, refractory autoimmune disorders, resolving all clinical and laboratory symptoms.

This treatment offers a promising alternative for patients who do not respond to conventional therapies like corticosteroids or cytotoxic drugs, highlighting its potential as a key therapeutic option in difficult cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). Arzoo, K., Sadeghi, S., Liebman, HA.[2019]

In a study of 604 patients with rheumatoid arthritis who had inadequate responses to a previous TNF inhibitor, switching to rituximab resulted in a significantly greater improvement in disease activity scores compared to switching to another TNF inhibitor after 6 months.

The effectiveness of rituximab was particularly notable in seropositive patients and those who switched due to inefficacy of the first TNF inhibitor, while the overall safety profile was similar between the two treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study. Emery, P., Gottenberg, JE., Rubbert-Roth, A., et al.[2022]

In a study involving 369 patients with rheumatoid arthritis, switching from adalimumab to sarilumab monotherapy led to significant improvements in disease activity, with 47.1% of switch patients showing meaningful changes in their Disease Activity Score by week 12 of the open-label extension.

The safety profile of sarilumab remained consistent with previous reports, showing no unexpected safety issues, and patients who continued on sarilumab experienced sustained benefits in disease management over the 48-week period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension. Burmester, GR., Strand, V., Rubbert-Roth, A., et al.[2020]

Rituximab, an anti-CD20 monoclonal antibody, effectively suppresses inflammation in autoimmune diseases by promoting the elimination of B cells, which are involved in the inflammatory response.

The proposed mechanism of action for rituximab involves the formation of decoy immune complexes that attract effector cells, reducing their recruitment to sites of inflammation and thereby decreasing tissue damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug insight: the mechanism of action of rituximab in autoimmune disease--the immune complex decoy hypothesis. Taylor, RP., Lindorfer, MA.[2015]

Citations

1. withpower.com withpower.com/trial/phase-2-autoimmune-diseases-10-2024-c3aab

AD-PluReceptor + Tafasitamab for Autoimmune Disorders Research shows that targeting B cell-stimulating molecules like BAFF and APRIL, which are involved in autoimmune diseases, can be effective. Drugs like ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06434363

Phase I/II Study of AD-PluReceptor Plus Tafasitamab-cxix ... The goal of Phase 1 is to find the recommended dose of AD-PluReceptor-NK cells in combination with tafasitamab and lymphodepleting chemotherapy that can be ...

3. oncodaily.com oncodaily.com/drugs/tafasitamab-cxix-monjuvi-patient-version

Tafasitamab-cxix (Monjuvi): What Patients Need to Know ... Real-Life Effectiveness​​ Data from real-world use confirms the clinical trial findings. Tafasitamab continues to deliver durable responses in ...

4. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-late-breaking-tafasitamab-monjuvir-data-ash-2024

Incyte Late-Breaking Tafasitamab (Monjuvi®) Data at ASH ... Patients treated with tafasitamab achieved a median PFS by investigator assessment of 22.4 months compared to 13.9 months in the control arm ( ...

5. healthtree.org healthtree.org/follicular-lymphoma/community/articles/tafasitamab-cxix-fda-approved-follicular-lymphoma

Tafasitamab-cxix (Monjuvi) FDA Approved for FL Tafasitamab-cxix, combined with rituximab and lenalidomide, is a newly approved one-year therapy for people with relapsed/refractory follicular lymphoma.