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

Trial Summary

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.

What data supports the effectiveness of the drug 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 belimumab, which inhibit BAFF, have been approved for conditions like systemic lupus erythematosus, suggesting that similar approaches could be beneficial for other autoimmune disorders. ^{1 2 3 4 5}

How is the drug Tafasitamab-cxix different from other treatments for autoimmune disorders?

Tafasitamab-cxix is unique because it is a monoclonal antibody that targets CD19, a protein on the surface of B cells, which are involved in autoimmune responses. This is different from other treatments like rituximab, which targets CD20, another B cell protein, offering a novel approach to modulating the immune system in autoimmune disorders. ^{2 3 5 6 7}

What is the purpose of this trial?

The goal of Safety Lead-In is to confirm the safety of tafasitamab when given to patients with SSc, SLE, and LN. 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 given to patients with the disease. The goal of Phase 2 is to learn if the dose of AD-PluReceptor-NK cells found in Phase 1 in combination with tafasitamab and lymphodepleting chemotherapy can help to control the disease.

Research Team

Chitra Hosing, MD

Principal Investigator

MDAnderson Cancer Center

Eligibility Criteria

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.

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

Positive ANA by immunofluorescence at titer ≥ 1:80

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

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

Treatment Details

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.

Participant Groups

Group I: Safety Lead-In Experimental Treatment 1 Intervention

Group II: Dose Expansion Experimental Treatment 3 Interventions

Group III: Dose Escalation Experimental Treatment 3 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+

Findings from Research

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]

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]

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, 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 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]

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]

References

1. United States 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. [2022]

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

Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases. [2022]

3. England 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. [2022]

4. England 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. [2020]

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

Clinical effects and safety of rituximab for treatment of refractory pediatric autoimmune diseases. [2019]

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

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

7. England pubmed.ncbi.nlm.nih.gov

Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). [2019]