Tafasitamab + Lenalidomide for CNS Lymphoma

Overseen By Hayley Wallace

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: James Rubenstein

Must not be taking: Anti-CD19 therapy

Disqualifiers: HIV, CNS PTLD, uncontrolled infection, others

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

Compensation: Varies

Number of Visits: Unknown

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of lenalidomide and Tafasitamab in patients with brain cancer that has returned after previous treatments. Lenalidomide, a derivative of thalidomide, is known to boost the immune system and directly target cancer cells, potentially improving drug delivery to the brain.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received systemic anti-cancer therapies within 2 weeks, radiation within 1 week, or antibody therapy within 4 weeks before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Tafasitamab and Lenalidomide for treating CNS Lymphoma?

Tafasitamab combined with Lenalidomide has shown effectiveness in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with studies indicating improved survival outcomes compared to other treatments. In particular, the combination demonstrated a significant overall survival benefit and durable responses in patients who were not eligible for stem cell transplants. ^{1 2 3 4 5}

What safety data exists for Tafasitamab and Lenalidomide treatment?

Tafasitamab and Lenalidomide have been studied together for treating certain types of lymphoma, and common side effects include infections, blood disorders, and digestive issues. These side effects were generally manageable, and no new safety concerns were found in long-term studies. Lenalidomide, a related drug, has reduced nerve and blood clot side effects compared to its predecessor, thalidomide. ^{1 2 5 6 7}

How is the drug combination of Tafasitamab and Lenalidomide unique for treating CNS Lymphoma?

The combination of Tafasitamab and Lenalidomide is unique because Tafasitamab is an anti-CD19 monoclonal antibody that enhances the immune system's ability to target cancer cells, and when combined with Lenalidomide, it has shown long-term clinical benefits and durable responses in similar conditions like diffuse large B-cell lymphoma (DLBCL). This combination is particularly beneficial for patients who are not eligible for stem cell transplants. ^{1 2 4 5 8}

Research Team

James Rubenstein, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

Adults with relapsed B-cell CNS lymphoma, including those who've had stem cell transplants but not recent anti-cancer treatments or certain other therapies. Must have good organ function and no serious medical issues that could affect safety. Women of childbearing age must agree to pregnancy testing and use contraception.

Inclusion Criteria

I have another cancer, but it won't affect this trial's treatment.

I had hepatitis C but am cured, or I'm being treated with no detectable virus.

I have CNS lymphoma in the brain and have undergone at least one treatment.

Exclusion Criteria

I am not pregnant or breastfeeding, and if of child-bearing potential, I am using effective birth control.

I have never received anti-CD19 or CAR-T therapy.

I haven't had cancer treatments like chemotherapy, radiation, or antibody therapy in the specified time before starting this trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive Tafasitamab and Lenalidomide to determine the maximum tolerated dose and recommended phase 2 dose

Up to 1 cycle (28 days)

Multiple visits for dosing and monitoring

Phase 2 Treatment

Participants receive Tafasitamab and Lenalidomide at the recommended phase 2 dose to evaluate clinical benefit

Up to 3 months

Multiple visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Regular follow-up visits

Treatment Details

Interventions

• Lenalidomide
• Tafasitamab

Trial Overview The trial is exploring the effectiveness of Tafasitamab combined with Lenalidomide in patients with relapsed CNS lymphoma. It's an open-label study, meaning everyone knows what treatment they're getting, focusing on how well this combination crosses the blood-brain barrier.

Participant Groups

Group I: Phase 2 (Tafasitamab, Lenalidomide) Experimental Treatment 2 Interventions

Participants will be given 12mg of Tafasitamab on days 1, 4, 8, 15, and 22 of cycle 1, days 1, 8, 15, and 22 of cycles 2 \& 3, and days 1 and 15 for any cycle thereafter. Participants will also be given daily Lenalidomide on days 1-21 of each cycle at the recommended phase 2 dose.

Group II: Phase 1 (Tafasitamab, Lenalidomide) Experimental Treatment 2 Interventions

Participants will be given 12mg of Tafasitamab on days 1, 4, 8, 15, and 22 of cycle 1, days 1, 8, 15, and 22 of cycles 2 \& 3, and days 1 and 15 for any cycle thereafter. Participants will also be given daily Lenalidomide on days 1-21 of each cycle.

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?

James Rubenstein

Lead Sponsor

Trials

3

Recruited

70+

Incyte Corporation

Industry 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

Findings from Research

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]

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]

In a study comparing tafasitamab combined with lenalidomide to lenalidomide alone in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), the combination therapy showed a significantly higher overall response rate of 67.1% compared to 34.2% for lenalidomide monotherapy.

The combination therapy also resulted in a higher complete response rate of 39.5% versus 13.2% for lenalidomide alone, indicating that tafasitamab enhances the efficacy of lenalidomide in treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a Real-world Lenalidomide Monotherapy Cohort in Relapsed or Refractory Diffuse Large B-cell Lymphoma. Zinzani, PL., Rodgers, T., Marino, D., 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]

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]

Lenalidomide, a derivative of thalidomide, has improved potency and a better side-effect profile, particularly with reduced neurologic toxicity compared to its predecessor.

While lenalidomide shows promise in treating conditions like myelodysplastic syndrome and multiple myeloma, there are still concerns about pro-thrombotic effects, especially when used with dexamethasone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: an immunomodulatory drug. Crane, E., List, A.[2018]

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. 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]

2. 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]

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

RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a Real-world Lenalidomide Monotherapy Cohort in Relapsed or Refractory Diffuse Large B-cell Lymphoma. [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. New Zealand pubmed.ncbi.nlm.nih.gov

Tafasitamab: First Approval. [2022]

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. England pubmed.ncbi.nlm.nih.gov

Lenalidomide: an immunomodulatory drug. [2018]

8. 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]