SGN-35 for Skin Lymphomas

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, others

Disqualifiers: Infections, HIV, Hepatitis, 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: 2

Duration: 6-12 months

79 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical research study is to learn if SGN-35 (brentuximab vedotin) can help to control ALCL, LyP or MF in patients with at least 1 of the 3 skin lymphomas. The safety of the study drug will also be studied.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) from previous treatments: at least 4 weeks for local radiation or systemic anticancer therapy, over 2 weeks for oral methotrexate or topical therapies, and at least 12 weeks for immunotherapy. Some medications, like corticosteroids, are restricted, but small doses for certain conditions are allowed.

What data supports the effectiveness of the drug SGN-35 for skin lymphomas?

Brentuximab vedotin, which is the drug SGN-35, has shown promising results in phase 2 trials for treating CD30+ Hodgkin lymphoma and anaplastic large cell lymphoma, which are similar to skin lymphomas like mycosis fungoides and Sézary syndrome. ^{1 2 3 4 5}

What safety data exists for SGN-35 (Brentuximab Vedotin) in humans?

SGN-35, also known as Brentuximab Vedotin, has been tested in clinical trials and is generally well tolerated in humans. Common mild side effects include nausea, fatigue, and fever, while more serious side effects can include infections like herpes zoster and pneumonia. The most common toxic effect is peripheral neuropathy (nerve damage), which is dose-dependent and often reversible. ^{6 7 8 9 10}

How is the drug SGN-35 different from other treatments for skin lymphomas?

SGN-35, also known as brentuximab vedotin, is unique because it is an antibody-drug conjugate that specifically targets CD30, a protein found on the surface of some lymphoma cells, delivering a potent chemotherapy directly to the cancer cells. This targeted approach can potentially reduce damage to healthy cells compared to traditional chemotherapy. ^{11 12 13 14 15}

Research Team

Auris O Huen, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with certain skin lymphomas (ALCL, LyP, or MF) that are CD30 positive and have not responded to previous treatments like radiation therapy or chemotherapy. They must be in good enough health for systemic therapy as judged by the doctor, not pregnant, willing to use contraception, and able to follow study procedures.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

I can attend all required study visits for tests and treatment management.

I am not pregnant and agree to use birth control during the study.

Exclusion Criteria

I do not have any serious health conditions that would interfere with treatment.

I have dementia or changes in my mental status.

I do not have severe infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive brentuximab vedotin intravenously on Day 1 of each 21-day cycle, for up to 8 cycles, with possible extension based on response

6-12 months

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including physical exams, questionnaires, and imaging

3-4 weeks

1 visit (in-person)

Long-term Follow-up

Long-term follow-up on disease status and any study-related nerve damage, with visits every 12-16 weeks for the first 2 years, then every 6 months up to 5 years

5 years

Treatment Details

Interventions

• SGN-35

Trial Overview The trial is testing SGN-35 (brentuximab vedotin) for its effectiveness in controlling three types of skin lymphomas: ALCL, LyP, and MF. It also aims to evaluate the safety profile of this drug in patients who have these conditions.

Participant Groups

Group I: SGN-35 Experimental Treatment 1 Intervention

1.8 mg/kg intravenously Day 1 of 21-day cycle.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Findings from Research

In a study of 118 patients with cutaneous T-cell lymphomas (CTCL), including mycosis fungoides (MF) and Sézary syndrome (SS), the overall survival for MF patients was 17.7 years, while SS patients had a median survival of 3.5 years, indicating significant differences in outcomes based on the type of CTCL.

The most common treatments for MF included low-dose methotrexate and interferon-alpha, while SS patients often received bexarotene and extracorporeal photopheresis, highlighting the need for more innovative therapies to be integrated into earlier treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Analysis of 118 Patients With Cutaneous T-Cell Lymphomas: A Single-Center Experience. Polgárová, K., Polívka, J., Kodet, O., et al.[2022]

In a Phase 1 study involving 24 patients with refractory Hodgkin lymphoma or CD30(+) non-Hodgkin lymphoma, SGN-30 was found to be safe with mild adverse effects, and the maximum tolerated dose was not reached.

The treatment showed modest clinical activity, with one patient achieving a complete response and six others maintaining stable disease for 6 to 16 months, indicating potential effectiveness in targeting CD30(+) malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies. Bartlett, NL., Younes, A., Carabasi, MH., et al.[2021]

SGN-30, a chimeric antibody targeting CD30, shows promising efficacy, particularly in patients with primary cutaneous CD30-positive lymphoproliferative disease and in those with relapsed or refractory systemic anaplastic large-cell lymphoma.

The drug is well tolerated even in patients with a history of stem cell transplantation, and it may work synergistically with chemotherapy, although the optimal dosing schedule is still to be determined.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGN-30: a basis for the effective treatment of CD30 positive hematopoietic malignancies. Pinter-Brown, LC.[2019]

In a Phase II study involving 79 patients with refractory/recurrent Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL), SGN-30 showed modest clinical activity, particularly in ALCL, where 2 patients achieved complete responses and 5 had partial responses.

The treatment was found to be safe, with most adverse events being mild or moderate, indicating that SGN-30 can be administered weekly without significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II study of SGN-30 (anti-CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Forero-Torres, A., Leonard, JP., Younes, A., et al.[2022]

SGN-35, an antibody-drug conjugate targeting CD30, effectively releases the potent drug MMAE inside CD30(+) cancer cells, achieving high intracellular concentrations that contribute to its therapeutic effects.

MMAE not only kills CD30(+) cells but can also diffuse to and exert cytotoxic effects on neighboring CD30(-) cells, enhancing the overall antitumor activity of SGN-35 in mixed tumor environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Okeley, NM., Miyamoto, JB., Zhang, X., et al.[2021]

References

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

Brentuximab as a treatment for CD30+ mycosis fungoides and Sézary syndrome. [2022]

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

Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). [2022]

3. England pubmed.ncbi.nlm.nih.gov

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. [2022]

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

Enhancement of antibody-dependent cellular cytotoxicity is associated with treatment response to extracorporeal photopheresis in Sézary syndrome. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Retrospective Analysis of 118 Patients With Cutaneous T-Cell Lymphomas: A Single-Center Experience. [2022]

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

A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies. [2021]

7. England pubmed.ncbi.nlm.nih.gov

SGN-30: a basis for the effective treatment of CD30 positive hematopoietic malignancies. [2019]

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

A Phase II study of SGN-30 (anti-CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma. [2022]

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

Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Therapeutic Use of Brentuximab Vedotin in CD30+ Hematologic Malignancies. [2019]

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

Primary cutaneous histiocyte and neutrophil-rich CD30+ and CD56+ anaplastic large-cell lymphoma with prominent angioinvasion and nerve involvement in the forehead and scalp of an immunocompetent woman. [2017]

12. England pubmed.ncbi.nlm.nih.gov

CD30-positive cutaneous extranodal natural killer/T-cell lymphoma: clinicopathological features and survival outcomes. [2019]

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

Unusual cutaneous lymphomas. [2019]

14. Japan pubmed.ncbi.nlm.nih.gov

[Primary cutaneous lymphoma--mycosis fungoides]. [2015]

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

Radiographically negative, asymptomatic, sentinel lymph node positive cutaneous T-cell lymphoma in a 3-year-old male: a case report. [2021]