Tafasitamab + Lenalidomide for Non-Hodgkin's Lymphoma

(MINDway Trial)

Not currently recruiting at 88 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs, tafasitamab (an antibody therapy) and lenalidomide (an immunomodulatory drug), for individuals with diffuse large B-cell lymphoma (DLBCL) that has recurred or resisted previous treatments. The study aims to determine the safety of this combination and how the body processes the drugs. It seeks participants who have undergone one to three prior treatments for DLBCL, including at least one targeting the CD20 protein, and who are ineligible for high-dose chemotherapy with stem cell transplant. Those who have relapsed or not responded to earlier therapies and cannot undergo intense salvage treatment may be suitable for this trial. As a Phase 1, Phase 2 trial, the study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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.

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

Research has shown that the combination of tafasitamab and lenalidomide is generally safe for patients. One study found that using these two drugs together is safe over the long term, with most people not experiencing serious side effects.

Previously, researchers tested tafasitamab with lenalidomide in patients with diffuse large B-cell lymphoma, a type of blood cancer. Reports from these tests suggested that the treatment is usually manageable, with many patients handling it well.

This treatment is already approved for other conditions, indicating that, when used as directed, the combination is considered safe for many people.

As always, some side effects may occur, and discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Tafasitamab and Lenalidomide for Non-Hodgkin's Lymphoma because it offers a fresh approach to tackling this challenging cancer. Unlike traditional therapies that might only target the cancer cells directly, Tafasitamab works by modifying the immune system to better recognize and attack the cancer cells. This makes it a compelling option, especially when combined with Lenalidomide, which also modulates the immune response. Together, these drugs could potentially provide a more robust treatment option with longer-lasting effects than current standard therapies.

What evidence suggests that the combination of Tafasitamab and Lenalidomide could be effective for Non-Hodgkin's Lymphoma?

Research has shown that combining tafasitamab with lenalidomide may help treat relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). In this trial, participants will receive both tafasitamab and lenalidomide. One study found that this combination led to lasting improvements and longer survival in patients. Another study demonstrated that lenalidomide can enhance the cancer-fighting effects of tafasitamab by 3 to 5 times. These findings suggest that this combination could effectively treat this type of lymphoma. ^{3 6 7 8 9}

Who Is on the Research Team?

Incyte Medical Director

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8409029/

Long-term outcomes from the phase II L-MIND study of ... This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06299553

Study to Evaluate the Effectiveness of Tafasitamab in ... The PRO-MIND study is an Italian, multicenter, prospective observational cohort study to evaluate the effectiveness and the safety of tafasitamab in combination ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10841029/

Tafasitamab for the treatment of patients with diffuse large B ... Results of an in vitro study showed that pre-treatment of macrophages with lenalidomide enhanced tafasitamab-associated cytotoxicity by 3–5 fold ...

4. ashpublications.org ashpublications.org/blood/article/142/26/2327/498041/Tafasitamab-and-lenalidomide-in-large-B-cell

Tafasitamab and lenalidomide in large B-cell lymphoma Tafasitamab and lenalidomide in large B-cell lymphoma: real-world outcomes in a multicenter retrospective study

5. tandfonline.com tandfonline.com/doi/full/10.1080/14712598.2021.1884677

Tafasitamab for the treatment of relapsed or refractory ... Tafasitamab, an anti-CD19 monoclonal antibody, in combination with lenalidomide has demonstrated promising efficacy for patients with R/R DLBCL who are ...

6. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-tafasitamab-cxix-relapsed-or-refractory-follicular-lymphoma

FDA approves tafasitamab-cxix for relapsed or refractory ... The recommended tafasitamab-cxix dose is 12 mg/kg as an intravenous infusion for a maximum of 12 cycles with lenalidomide and rituximab.

7. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-fda-approval-monjuvir-tafasitamab-cxix

Incyte Announces FDA Approval of Monjuvi® (tafasitamab- ... Monjuvi (tafasitamab-cxix) in combination with rituximab and lenalidomide is the first FDA-approved CD19- and CD20-targeted immunotherapy combination for adult ...

8. ashpublications.org ashpublications.org/bloodadvances/article/9/19/4924/546204/Tafasitamab-plus-lenalidomide-as-salvage-therapy

Tafasitamab plus lenalidomide as salvage therapy in diffuse ... Approximately 20% to 25% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse, and ∼10% to 15% are refractory to frontline ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37646664/

final 5-year efficacy and safety findings in the phase II L-MIND ... This final 5-year analysis of L-MIND demonstrates that the immunotherapy combination of tafasitamab and lenalidomide is well tolerated and has long-term ...