Pembrolizumab + Mogamulizumab for Cutaneous T-Cell Lymphoma

Overseen By Cancer AnswerLine

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: Immunosuppressants, Checkpoint inhibitors

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, 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: 1

Duration: Up to 2 years

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, pembrolizumab (an immunotherapy drug) and mogamulizumab (an antibody therapy), for individuals with advanced-stage cutaneous T-cell lymphoma (a type of skin cancer). The goal is to determine if this combination benefits patients who have not responded well to previous treatments. Participants will receive these medicines at specific intervals over up to two years. This trial suits individuals with this type of lymphoma in stages IIB to IVB who have tried at least one other treatment without success. 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 does not specify if you need to stop taking your current medications. However, if you are on systemic steroids, the dose must be less than the equivalent of 10 mg/day of prednisone. It's best to discuss your specific medications with the trial team.

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

Studies have shown that combining pembrolizumab and mogamulizumab is generally well-tolerated in previous trials. Both treatments are immunotherapies, helping the body's immune system fight cancer.

Research indicates that pembrolizumab is usually well-tolerated. Common side effects include fatigue, skin rash, and itching, while more serious side effects are less common.

Mogamulizumab has been used in other studies with patients who have similar conditions, showing effective results against cancer with acceptable side effects. Common side effects include skin rash, mild allergic-like reactions during administration, and fatigue. Serious side effects can occur but are less common.

This ongoing trial is in its second phase, indicating some evidence of safety from earlier studies. This phase further confirms the treatment's safety and effectiveness. Participants will be closely monitored to manage any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for Cutaneous T-Cell Lymphoma (CTCL) focus on targeting cancer cells directly using chemotherapy or radiation. However, pembrolizumab and mogamulizumab work differently by harnessing the body's immune system to fight the cancer. Pembrolizumab works as a checkpoint inhibitor, blocking the proteins that prevent T-cells from attacking cancer cells, while mogamulizumab targets a specific protein on the surface of certain immune cells, potentially enhancing their ability to kill cancer cells. Researchers are excited about these treatments because they offer a novel approach that could lead to more effective and lasting responses with potentially fewer side effects compared to traditional therapies.

What evidence suggests that this treatment might be an effective treatment for CTCL?

Research has shown that combining pembrolizumab and mogamulizumab could be promising for treating advanced cutaneous T-cell lymphoma (CTCL). This trial will evaluate the effectiveness of these treatments together. Previous studies found that this combination can significantly improve survival for patients with advanced CTCL. Mogamulizumab has demonstrated a strong ability to fight tumors and is considered a new treatment with manageable side effects. Pembrolizumab, a type of immunotherapy, helps the body's immune system fight cancer cells more effectively. Together, these treatments have shown potential in improving outcomes for CTCL patients, offering hope for those whose condition has returned or is not responding to other treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Ryan Wilcox, MD

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced-stage, relapsed/refractory Cutaneous T-cell Lymphoma (CTCL) who have failed at least one systemic therapy can join. They must have measurable disease not treated by radiation within the last week, be expected to live more than 6 months, and function relatively well daily. Participants need proper organ function and women of childbearing age must test negative for pregnancy and agree to contraception.

Inclusion Criteria

I can provide tissue samples from a previous procedure or am willing to undergo a biopsy.

I've had at least one systemic therapy for cancer and recovered from its side effects.

My recent tests show my organs are functioning well.

Exclusion Criteria

Treatment with any investigational drug or investigation device within 30 days prior to registration.

I have not been treated with drugs like pembrolizumab or mogamulizumab.

I have not had active treatment for another cancer, except skin or in situ cancers, in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and mogamulizumab. Pembrolizumab is administered on Day 1 of each 6-week cycle. Mogamulizumab is administered on Days 1, 8, 15, and 22 of Cycle 1, and on Days 1, 15, and 29 of subsequent cycles.

Up to 2 years

Cycle 1: 4 visits (in-person), Cycle 2+: 3 visits (in-person) per cycle

Response Assessment

Subjects undergo a response assessment prior to Cycle 3 and every 2 cycles thereafter to evaluate treatment effectiveness.

Throughout treatment

Observation

If a subject achieves a complete response (CR) after 3 months of treatment, they may enter an observation period after an additional 6 months of therapy. Repeat disease evaluation is required prior to discontinuation.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment. Subjects who progress during the observation period may be eligible for up to an additional 9 cycles (1 year) of treatment.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Mogamulizumab
• Pembrolizumab

Trial Overview The trial tests a combination of two drugs: Pembrolizumab and Mogamulizumab in patients with CTCL. It's an open-label phase II study where everyone gets both drugs in cycles lasting six weeks. Responses are checked before cycle three and every two cycles after that. Treatment continues unless there's progression or unacceptable side effects for up to two years.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 2 Interventions

Pembrolizumab 400mg via IV over 30 minutes on Day 1 of each cycle (6 weeks) Mogamulizumab 1mg/kg via IV over a least 60 minutes Cycle 1: Days 1, 8, 15, and 22 Cycle 2+: Days 1, 15, and 29 Each cycle lasts 6 weeks with a maximum of 18 cycles If a subject achieves a complete response (CR) after 3 months of study treatment (2 cycles), they will continue study therapy for an additional 6 months (4 cycles). If a confirmed and persistent CR they may discontinue study treatment and enter an observation period. Subjects who progress during the observation period may be eligible for up to an additional 12 cycles of pembrolizumab and mogamulizumab

Mogamulizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Poteligeo for:

• Mycosis fungoides
• Sézary syndrome

Approved in United States as Poteligeo for:

• Mycosis fungoides
• Sézary syndrome

Approved in Canada as Poteligeo for:

• Mycosis fungoides
• Sézary syndrome

Approved in Japan as Poteligeo for:

• Adult T-cell leukemia-lymphoma
• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Hoosier Cancer Research Network

Collaborator

Trials

69

Recruited

3,800+

Published Research Related to This Trial

Mogamulizumab, a novel monoclonal antibody, effectively targets and treats mycosis fungoides and Sèzary syndrome by binding to C-C chemokine receptor 4, enhancing the immune system's ability to attack malignant T-cells.

In a real-life clinical setting in Italy, 12 patients with these skin lymphomas showed significant improvement in symptoms and quality of life when treated with mogamulizumab, indicating its efficacy and manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian Real-Life Experience on the Use of Mogamulizumab in Patients with Cutaneous T-Cell Lymphomas. Caruso, L., Castellino, A., Dessì, D., et al.[2022]

Mogamulizumab-kpkc significantly improves progression-free survival in patients with relapsed or refractory mycosis fungoides and Sézary syndrome, showing a PFS of 7.7 months compared to 3.1 months with vorinostat in a phase III trial.

While mogamulizumab-kpkc is effective, it carries risks of serious side effects, including increased risk of severe acute graft-vs.-host disease and other complications, which must be weighed against its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab-kpkc: A Novel Therapy for the Treatment of Cutaneous T-Cell Lymphoma. Watson, S., Marx, JB.[2021]

In the phase III MAVORIC trial, patients with cutaneous T-cell lymphoma treated with mogamulizumab had significantly longer progression-free survival compared to those receiving vorinostat, a standard therapy.

Mogamulizumab also resulted in higher response rates and improved quality of life for patients, indicating its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab Tops Standard of Care for CTCL. [2019]

Mogamulizumab is a humanized monoclonal antibody that specifically targets the CCR4 receptor, which plays a role in the progression of cutaneous T-cell lymphoma (CTCL).

Clinical trials have shown promising results for mogamulizumab in treating CTCL, indicating its potential as an effective therapeutic option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab for the treatment of cutaneous T-cell lymphoma: recent advances and clinical potential. Duvic, M., Evans, M., Wang, C.[2020]

Mogamulizumab, an anti-CCR4 monoclonal antibody, not only targets and depletes Sézary cells in patients with Sézary syndrome but also helps restore effective immunity by reshaping both malignant and benign T cell populations, as observed in a study of 26 patients.

The treatment led to a significant decrease in exhausted benign T cells and activated regulatory T cells within the first four weeks, while long-term follow-up showed an increase in CD8+ and naive CD4+ T cells, indicating a potential for improved immune function after therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab induces long-term immune restoration and reshapes tumour heterogeneity in Sézary syndrome. Roelens, M., de Masson, A., Andrillon, A., et al.[2022]

In a study of 13 patients with cutaneous T-cell lymphoma (CTCL), mogamulizumab treatment led to significant reductions in T cells, with a 57% decrease in total CD3+ T cells and up to 75% in aberrant T cell populations after four treatment cycles.

The reduction in aberrant T cells was noticeable after just one dose of mogamulizumab, indicating its potential effectiveness, although no clear correlation was found between the decrease in aberrant T cells and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of mogamulizumab on the aberrant T cell population in the peripheral blood - A monocentric retrospective analysis. Gosmann, J., Bielefeld, A., Schmitz, FJ., et al.[2023]

In a phase 3 trial involving 372 patients with relapsed cutaneous T-cell lymphoma, mogamulizumab significantly improved progression-free survival compared to vorinostat, with a median of 7.7 months versus 3.1 months, respectively.

Both treatments had similar rates of severe adverse events (41% in each group), indicating that mogamulizumab is not only more effective but also has a comparable safety profile to vorinostat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Kim, YH., Bagot, M., Pinter-Brown, L., et al.[2023]

In the phase 3 MAVORIC study, mogamulizumab demonstrated superior efficacy compared to vorinostat in treating mycosis fungoides (MF) patients, particularly in those with higher baseline blood tumor burden, showing significant improvements in progression-free survival (PFS) and time-to-next-treatment (TTNT).

Mogamulizumab-treated patients with MF showed a better overall response rate (ORR) and PFS as blood involvement increased, indicating that higher blood tumor burden may correlate with better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of blood involvement on efficacy and time to response with mogamulizumab in mycosis fungoides and Sézary syndrome. Beylot-Barry, M., Booken, N., Weishaupt, C., et al.[2023]

Mogamulizumab is an effective treatment for adults with relapsed or refractory cutaneous T-cell lymphoma (CTCL), specifically mycosis fungoides and Sézary syndrome, after they have undergone at least one prior systemic therapy.

Patients may experience infusion reactions and drug eruptions, which necessitate quick diagnosis and management to ensure safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous T-Cell Lymphoma: Optimizing Care in Patients Receiving Anti-CCR4 Monoclonal Antibody Mogamulizumab. Tawa, M., Kopp, E., McCann, S., et al.[2020]

Citations

1. fidelity.com fidelity.com/news/article/default/202510220330BIZWIRE_USPR_____20251022_BW165640

Global Registry Data Show Meaningful Overall Survival ... Global Registry Data Show Meaningful Overall Survival Benefit in Patients with Advanced Cutaneous T-cell Lymphoma (CTCL) treated with POTELIGEO ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-10364

Pembrolizumab and Mogamulizumab for the Treatment of ... This phase II trial tests how well pembrolizumab in combination with mogamulizumab works in treating patients with cutaneous T-cell lymphomas.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8157723/

Safety and efficacy profile of mogamulizumab (Poteligeo) in ... Based on present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which is a novel therapy in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03309878

Study Details | NCT03309878 | Mogamulizumab and ... This phase I/II trial studies the best dose and side effects of mogamulizumab in combination with pembrolizumab and to see how well they work in treating ...

5. kkna.kyowakirin.com kkna.kyowakirin.com/media-center/new-data-from-mavoric-trial-sheds-light-on-key-characteristics-of-long-term-poteligeo-mogamulizumab-kpkc-responders-with-specific-subtypes-of-cutaneous-t-cell-lymphoma/

New Data from MAVORIC Trial Sheds Light on Key ... MAVORIC was a pivotal open-label, international, Phase 3, randomized controlled trial that evaluated the safety and efficacy of mogamulizumab versus standard-of ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/hon.3292

Safety and effectiveness of mogamulizumab in relapsed or ... Safety and effectiveness of mogamulizumab in relapsed or refractory CC chemokine receptor 4-positive peripheral T-cell lymphoma and relapsed or ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10493109/

Advances in Immunotherapy for the Treatment of Cutaneous T ... Combinations of immunotherapeutic antibodies have demonstrated safety in other malignancies, such as BV and PD-1 antibodies in Hodgkin lymphoma ...