Pembrolizumab + Mogamulizumab for Cutaneous T-Cell Lymphoma

Overseen by Ryan Wilcox, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: Immunosuppressants, Checkpoint inhibitors

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

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is an open-label, single-arm, multicenter, phase II study combining pembrolizumab and mogamulizumab in patients with advanced-stage, relapsed or refractory CTCL Each cycle will equal 6 weeks. Pembrolizumab will be administered on Day 1 of each cycle. Mogamulizumab will be administered on Day 1, 8, 15, and 22 of Cycle 1. For Cycle 2 and subsequent cycles, mogamulizumab will be administered on Day 1, 15 and 29 of each cycle. Subjects will undergo a response assessment prior to Cycle 3 and every 2 cycles thereafter. Subjects will continue study treatment until documented progression, unacceptable toxicity, or any other condition for discontinuation is met in protocol. A maximum of 2 years of study treatment may be administered. If a subject achieves a complete response (CR) per mSWAT criteria 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 is met, they may discontinue study treatment and enter an observation period in protocol. Repeat disease evaluation is required prior to study therapy discontinuation. Subjects who progress during the observation period may be eligible for up to an additional 9 cycles (1 year) of pembrolizumab and mogamulizumab.

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.

What data supports the effectiveness of the drug combination Pembrolizumab and Mogamulizumab for Cutaneous T-Cell Lymphoma?

Research shows that mogamulizumab, one of the drugs in the combination, significantly improves progression-free survival and quality of life in patients with cutaneous T-cell lymphoma compared to standard treatments. It effectively controls the disease in various body sites and improves symptoms and overall quality of life. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Mogamulizumab safe for humans?

Mogamulizumab has been shown to be generally safe in humans, with common side effects including rash, fatigue, and diarrhea. However, it can increase the risk of severe complications like graft-vs.-host disease if used before certain transplants. The overall safety profile is considered manageable, but the treatment is costly and benefits may be short-term. ^{1 2 5 6 7}

How is the drug combination of Pembrolizumab and Mogamulizumab unique for treating cutaneous T-cell lymphoma?

This drug combination is unique because Mogamulizumab is a first-in-class monoclonal antibody that targets a specific receptor (CCR4) on cancer cells, enhancing the immune system's ability to attack these cells, while Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and fight cancer cells more effectively. ^{3 5 6 8 9}

Research Team

Ryan Wilcox, MD

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

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 am 18 years old or older.

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.

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.

Trial Timeline

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

Treatment Details

Interventions

• Mogamulizumab (Monoclonal Antibodies)
• Pembrolizumab (Monoclonal Antibodies)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Findings from Research

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 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, 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]

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 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

The effect of mogamulizumab on the aberrant T cell population in the peripheral blood - A monocentric retrospective analysis. [2023]

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

Mogamulizumab Tops Standard of Care for CTCL. [2019]

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Mogamulizumab induces long-term immune restoration and reshapes tumour heterogeneity in Sézary syndrome. [2022]

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

Italian Real-Life Experience on the Use of Mogamulizumab in Patients with Cutaneous T-Cell Lymphomas. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Mogamulizumab for the treatment of cutaneous T-cell lymphoma: recent advances and clinical potential. [2020]

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

Mogamulizumab-kpkc: A Novel Therapy for the Treatment of Cutaneous T-Cell Lymphoma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Impact of blood involvement on efficacy and time to response with mogamulizumab in mycosis fungoides and Sézary syndrome. [2023]

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

Cutaneous T-Cell Lymphoma: Optimizing Care in Patients Receiving Anti-CCR4 Monoclonal Antibody Mogamulizumab. [2020]