Tafasitamab + Lenalidomide for Non-Hodgkin's Lymphoma

(MINDway Trial)

Recruiting at 63 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Incyte Corporation

Must be taking: CD20-targeted therapy

Must not be taking: IMiDs

Disqualifiers: Other lymphoma, HIV, hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 months

53 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of two drugs, Tafasitamab and Lenalidomide, given through an infusion. It targets patients with a specific type of lymphoma who have not responded to other treatments and cannot undergo more aggressive therapies. The treatment works by attacking cancer cells and boosting the immune system. Both drugs have shown effectiveness in treating this type of lymphoma.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as CD20-targeted therapy, chemotherapy, and other lymphoma-specific treatments, at least 14 days before starting the study. If you are on any of these treatments, you will need to discontinue them before participating.

What data supports the effectiveness of the drug combination Tafasitamab and Lenalidomide for Non-Hodgkin's Lymphoma?

The combination of Tafasitamab and Lenalidomide has shown effectiveness in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with a 57.5% overall response rate and a 41.3% complete response rate in a 5-year study. Additionally, this combination improved survival outcomes compared to other treatments like polatuzumab vedotin+bendamustine+rituximab and rituximab+lenalidomide, and had comparable outcomes to CAR-T therapies. ^{1 2 3 4 5}

Is the combination of Tafasitamab and Lenalidomide safe for humans?

The combination of Tafasitamab and Lenalidomide has been shown to be generally safe in humans, with manageable side effects. Common side effects include infections, blood disorders, and gastrointestinal issues, but no new safety concerns have been identified in long-term studies. ^{1 2 3 6 7}

How is the drug combination of Tafasitamab and Lenalidomide unique for treating Non-Hodgkin's Lymphoma?

The combination of Tafasitamab and Lenalidomide is unique because it is the first therapy approved as a second-line treatment for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for stem cell transplantation. Tafasitamab is a humanized antibody that targets CD19 on B-cells, and when combined with Lenalidomide, it shows a synergistic effect, leading to durable responses and improved survival outcomes compared to some other treatments. ^{1 2 3 5 7}

Research Team

Incyte Medical Director

Principal Investigator

Incyte Corporation

Eligibility Criteria

Adults with Diffuse Large B-Cell Lymphoma (DLBCL) who have tried 1-3 treatments but can't have high-dose chemo with stem-cell transplant. They need a confirmed diagnosis, at least one measurable site of cancer, and their major organs must function well. Can't join if they've had certain other cancers, severe diseases, or are HIV positive.

Inclusion Criteria

I have had CD19 targeted therapy before and my lymphoma is still CD19 positive.

I have a tumor visible on PET scan that is at least 1.5 cm by 1.0 cm.

I am able to understand and sign the consent form.

Exclusion Criteria

My cancer affects the central nervous system.

I have had blood clots and cannot take medication to prevent them during treatment.

History of hypersensitivity to compounds of similar biological or chemical composition to tafasitamab IMiDs® and/or the excipients contained in the study treatment formulations

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of tafasitamab and lenalidomide until disease progression, unacceptable toxicity, or discontinuation. Lenalidomide is given for up to 12 cycles, after which tafasitamab continues as monotherapy.

Up to 12 months

Follow-up

Participants are monitored for safety, pharmacokinetics, and anti-tumor activity after treatment

1-3 years

Treatment Details

Interventions

• Lenalidomide
• Tafasitamab

Trial Overview The trial is testing Tafasitamab combined with Lenalidomide in patients with relapsed or refractory DLBCL. It's an open-label study to see how safe the treatment is and how the body processes it when given in a new dosing regimen.

Participant Groups

Group I: Treatment (Tafasitamab + Lenalidomide) Experimental Treatment 2 Interventions

Treatment: Tafasitamab will be combined with lenalidomide in R/R DLBCL patients. Dose: Cohort 1: The dose of tafasitamab will be level 1 high dose in combination with the approved dose Cohort 2: The dose of tafasitamab will be level 2 high dose in combination with the approved dose Expansion Cohort: The dose of tafasitamab will be the dose that is deemed safe and tolerable as determined from cohort 1 \& cohort 2 Treatment consisting of tafasitamab and lenalidomide combination will be administered until disease progression, unacceptable toxicity, or discontinuation for any other reason, whichever comes first. Lenalidomide can be given for up to 12 cycles in total, after which patients can continue with tafasitamab as monotherapy until progression or unacceptable toxicity.

Lenalidomide is already approved in European Union, United States for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

MorphoSys AG

Lead Sponsor

Trials

27

Recruited

6,600+

Findings from Research

Tafasitamab, an anti-CD19 monoclonal antibody, received accelerated approval in July 2020 for treating adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in combination with lenalidomide, marking it as the first second-line therapy approved for this patient group in the USA.

The drug is administered intravenously at a recommended dose of 12 mg per kg and is also being explored for use in other B-cell malignancies, indicating its potential versatility in treating various types of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab: First Approval. Hoy, SM.[2022]

In a phase 2 study involving 81 patients with relapsed or refractory diffuse large B-cell lymphoma, the combination of tafasitamab and lenalidomide resulted in a 60% objective response rate, with 43% achieving a complete response, indicating significant antitumor activity.

The treatment was generally well tolerated, although serious adverse events occurred in 51% of patients, with neutropenia being the most common, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Salles, G., Duell, J., González Barca, E., et al.[2020]

In the final 5-year analysis of the L-MIND study involving 80 patients with relapsed/refractory diffuse large B-cell lymphoma, the combination of tafasitamab and lenalidomide showed a significant objective response rate of 57.5%, with a complete response rate of 41.3%.

The treatment demonstrated long-term clinical benefits, with a median overall survival of 33.5 months and manageable adverse events, indicating that this immunotherapy combination is both effective and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: final 5-year efficacy and safety in the phase II L-MIND study. Duell, J., Abrisqueta, P., Andre, M., et al.[2023]

Tafasitamab plus lenalidomide (TAFA + LEN) showed significantly better overall survival (OS) and progression-free survival (PFS) compared to standard treatments like polatuzumab vedotin + bendamustine + rituximab (POLA + BR) and bendamustine + rituximab (BR) in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

The study found that TAFA + LEN was associated with longer duration of response (DOR) and higher complete response rates (CRR), indicating its potential as a more effective treatment option, although further validation through large randomized trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab Plus Lenalidomide Versus 3 Rituximab-Based Treatments for Non-Transplant Eligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Matching-Adjusted Indirect Comparison. Cordoba, R., Prawitz, T., Westley, T., et al.[2022]

In a study comparing tafasitamab+lenalidomide to other treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), significant overall survival benefits were observed against polatuzumab vedotin+bendamustine+rituximab and rituximab+lenalidomide, indicating tafasitamab+lenalidomide may be a more effective option.

When compared to CAR-T therapies, tafasitamab+lenalidomide showed comparable overall survival outcomes, suggesting it could be a viable alternative for patients who are ineligible for autologous stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RE-MIND2: comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola-BR), CAR-T therapies, and lenalidomide/rituximab (R2) based on real-world data in patients with relapsed/refractory diffuse large B-cell lymphoma. Nowakowski, GS., Yoon, DH., Mondello, P., et al.[2023]

Tafasitamab, a monoclonal antibody targeting CD19, showed a significant objective response rate of 56.8% in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) during the L-MIND clinical trial, with a median duration of response of 34.6 months.

The treatment was associated with notable adverse events, particularly infections (72.8% of patients) and blood disorders (65.4%), indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Tafasitamab in Combination With Lenalidomide for the Treatment of Adult Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma. Delgado, J., Papadouli, I., Sarac, SB., et al.[2021]

In the phase II L-MIND study, tafasitamab combined with lenalidomide showed a 57.5% objective response rate in patients with relapsed/refractory diffuse large B-cell lymphoma, with a complete response in 40% of patients after more than 35 months of follow-up.

The treatment demonstrated a median overall survival of 33.5 months and a median duration of response of 43.9 months, with no unexpected toxicities, indicating a favorable safety and efficacy profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Duell, J., Maddocks, KJ., González-Barca, E., et al.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Tafasitamab: First Approval. [2022]

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

Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. [2020]

3. Italy pubmed.ncbi.nlm.nih.gov

Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: final 5-year efficacy and safety in the phase II L-MIND study. [2023]

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

Tafasitamab Plus Lenalidomide Versus 3 Rituximab-Based Treatments for Non-Transplant Eligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Matching-Adjusted Indirect Comparison. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

RE-MIND2: comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola-BR), CAR-T therapies, and lenalidomide/rituximab (R2) based on real-world data in patients with relapsed/refractory diffuse large B-cell lymphoma. [2023]

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

The European Medicines Agency Review of Tafasitamab in Combination With Lenalidomide for the Treatment of Adult Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma. [2021]

7. Italy pubmed.ncbi.nlm.nih.gov

Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. [2021]