Tafasitamab + Lenalidomide for Non-Hodgkin's Lymphoma

Overseen By Kim Sprenger

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressants, Antimicrobials

Disqualifiers: CNS disorder, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 6 months

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, tafasitamab and lenalidomide, to determine their safety and effectiveness in treating individuals with Large B Cell Lymphoma (a type of blood cancer) who have shown some response to a previous treatment called axi-cel. Participants will take lenalidomide daily for 21 days in each 28-day cycle and initially receive weekly tafasitamab infusions, which then switch to every two weeks. This study suits those diagnosed with specific types of large B-cell lymphoma and who have had partial or stable responses to previous CAR-T cell therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently receiving or have recently received any investigational study agent, you may not be eligible to participate.

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

Studies have shown that combining tafasitamab and lenalidomide is generally safe for patients with certain types of lymphoma. Research indicates that this treatment does not introduce new safety issues. Participants have experienced some common side effects, but these can be managed. Various studies have tested the treatment without causing unexpected problems, offering a reassuring picture of its safety for those considering joining a trial. ^{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 treating Non-Hodgkin's Lymphoma because it offers a novel approach compared to traditional therapies like chemotherapy and rituximab. Tafasitamab is a monoclonal antibody that specifically targets the CD19 antigen on B-cells, potentially improving the immune system's ability to attack cancer cells. Lenalidomide, on the other hand, modulates the immune response and enhances the effects of Tafasitamab. Together, they might provide a more effective and targeted treatment option, offering hope for improved outcomes in patients who have limited responses to existing therapies.

What evidence suggests that tafasitamab and lenalidomide might be an effective treatment for Large B Cell Lymphoma?

Research has shown that the combination of tafasitamab and lenalidomide, which participants in this trial will receive, may effectively treat lymphoma. One study found that patients with relapsed or hard-to-treat diffuse large B-cell lymphoma (a type of non-Hodgkin's lymphoma) who received this treatment lived without disease progression for an average of 11.3 months and had an overall survival of 24.8 months. Another study reported that patients lived without disease progression for 4.9 to 10.9 months and had an overall survival of 12.2 to 21.8 months. These results suggest that tafasitamab and lenalidomide together could help manage the disease for a significant time. Overall, evidence supports this treatment combination as a promising option for managing this type of lymphoma. ^{1 2 3 6 7}

Who Is on the Research Team?

Frederick Locke, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with Large B Cell Lymphoma who have previously undergone axicabtagene ciloleucel treatment. Participants will be involved in the study for approximately 12 months.

Inclusion Criteria

I am able to get out of my bed or chair and move around.

Baseline Oxygen Saturation >92% on room air

My PET/CT shows my disease is stable or partially improved after recent CAR-T therapy.

Exclusion Criteria

I have an autoimmune disease that has caused organ damage or needed strong medication in the last 2 years.

My heart is affected by lymphoma.

Patients who are currently receiving or who have received any investigational study agent ≤4 weeks prior to the screening visit are ineligible

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tafasitamab intravenously weekly for the first three 28-day cycles and every 2 weeks starting at Cycle 4. Lenalidomide is taken daily for 21 days out of each 28-day cycle for 6 cycles.

6 months

Weekly visits for the first 3 months, bi-weekly visits thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• Tafasitamab

Trial Overview The safety and effectiveness of combining two drugs, Tafasitamab and Lenalidomide, are being tested as a first salvage therapy option for patients with LBCL after initial treatment.

How Is the Trial Designed?

Group I: Tafasitamab and Lenalidomide Treatment Experimental Treatment 2 Interventions

Participants will receive the study drug, Tafasitamab, intravenously on a weekly basis for the first three 28-day cycles (Cycles 1-3) and then every 2 weeks starting at Cycle 4 onwards. Participants will take the study drug, Lenalidomide, once daily for 21 days out of each 28-day cycle for 6 cycles.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

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

Published Research Related to This Trial

Tafasitamab, a humanized monoclonal antibody targeting CD19, has been approved by the FDA for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients who cannot undergo autologous stem cell transplant, highlighting its efficacy in a challenging patient population.

The drug works by enhancing antibody-dependent cellular cytotoxicity and phagocytosis due to its modified Fc region, which increases its effectiveness in eliminating cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of tafasitamab in diffuse large B-cell lymphoma. Düll, J., Topp, M., Salles, G.[2023]

In a phase 1b study involving 66 adults with untreated diffuse large B-cell lymphoma (DLBCL), the combination of tafasitamab with R-CHOP showed promising efficacy, with an end-of-treatment overall response rate of 75.8% and a complete response rate of 72.7%.

The safety profile was manageable, with most treatment-emergent adverse events being grade 1 or 2, although higher rates of grade ≥3 neutropenia and thrombocytopenia were observed in the group receiving tafasitamab with lenalidomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of tafasitamab with or without lenalidomide added to first-line R-CHOP for DLBCL: the phase 1b First-MIND study. Belada, D., Kopeckova, K., Bergua Burgues, JM., et al.[2023]

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 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 RE-MIND2 study, patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) treated with tafasitamab plus lenalidomide showed significantly prolonged overall survival compared to those receiving standard systemic therapies, with a hazard ratio of 0.55.

When specifically compared to bendamustine plus rituximab and rituximab plus gemcitabine/oxaliplatin, tafasitamab plus lenalidomide demonstrated even greater survival benefits, with hazard ratios of 0.42 and 0.47, respectively, indicating its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Efficacy of Tafasitamab plus Lenalidomide versus Systemic Therapies for Relapsed/Refractory DLBCL: RE-MIND2, an Observational Retrospective Matched Cohort Study. Nowakowski, GS., Yoon, DH., Peters, A., 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 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]

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]

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 ... In patients with third- or later-line disease, the median PFS of 7.6 months and median OS of 15.5 months with tafasitamab plus lenalidomide are comparable with ...

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

Tafasitamab plus lenalidomide as salvage therapy in diffuse ... The median progression-free survival (PFS) was 4.9 and 10.9 months, and overall survival (OS) was 12.2 and 21.8 months, respectively for both ...

3. haematologica.org haematologica.org/article/view/haematol.2023.283480

Tafasitamab for patients with relapsed or refractory diffuse ... In conclusion, the final 5-year analysis of L-MIND showed clinically significant and enduring responses to tafasitamab + lenalidomide combination therapy, ...

4. onclive.com onclive.com/view/us-real-world-analysis-supports-clinical-benefit-of-tafasitamab-in-r-r-dlbcl

US Real-World Analysis Supports Clinical Benefit of ... Tafasitamab-cxix showed a progression-free survival of 11.3 months and overall survival of 24.8 months in relapsed/refractory DLBCL patients.

5. onco-hema.healthbooktimes.org onco-hema.healthbooktimes.org/article/137802-tafasitamab-and-lenalidomide-as-second-line-treatment-in-an-elderly-patient-with-a-primary-refractory-double-hit-diffuse-large-b-cell-lymphoma

Tafasitamab and Lenalidomide as Second-Line Treatment in ... The results suggested a significant OS benefit of tafasitamab plus lenalidomide compared with both Pola-BR (HR: 0.441 [95% CI: 0.203–0.956]; p= ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123015331

Safety and efficacy of tafasitamab with or without ... The novel combination of tafasitamab ± lenalidomide + R-CHOP showed signs of efficacy in patients with untreated DLBCL, with no new safety signals.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/761163Orig1s000MultidisciplineR.pdf

761163Orig1s000 - accessdata.fda.gov tafasitamab to the safety profile of tafasitamab/lenalidomide combination therapy in this population. The FDA's Assessment: The clinical ...