IPH4102 for Cutaneous T-Cell Lymphoma

(TELLOMAK Trial)

Not currently recruiting at 66 trial locations

Overseen By Innate Pharma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Innate Pharma

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Large cell transformation, CNS lymphoma, 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: Unknown

Duration: Expected average of 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IPH4102, an experimental therapy for specific skin-related blood cancers, known as Sezary Syndrome and Mycosis Fungoides. The goal is to evaluate the effectiveness and safety of IPH4102 for individuals with these conditions. Participants will receive the treatment regularly over a set period. Those who have experienced relapsed or hard-to-treat forms of these cancers and have tried at least two other treatments might be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial requires a minimum washout period (time without taking certain medications) of 3 weeks between the last dose of your previous systemic therapy and the first dose of IPH4102. This means you will need to stop taking your current systemic medications for at least 3 weeks before starting the trial treatment.

Is there any evidence suggesting that IPH4102 is likely to be safe for humans?

Research has shown that IPH4102 is generally safe for people. In previous studies, it proved safe for patients with cutaneous T-cell lymphoma, a type of skin cancer. Many patients, particularly those with Sézary Syndrome, tolerated the treatment well. Some side effects occurred, but they were not severe for most individuals. This suggests that IPH4102 is well-tolerated and shows promising results for those with this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cutaneous T-cell lymphoma?

Unlike the standard treatments for Cutaneous T-Cell Lymphoma, which often involve chemotherapy or radiation, IPH4102 is a monoclonal antibody that specifically targets KIR3DL2, a protein found on the surface of certain cancerous T-cells. This targeted approach means it could potentially offer a treatment option with fewer side effects because it aims directly at the cancer cells rather than affecting the entire body. Researchers are excited about IPH4102 because it represents a novel way to tackle the disease, focusing on a specific mechanism of action that might improve outcomes for patients with Mycosis Fungoides and Sézary Syndrome, particularly in cases where traditional treatments have failed.

What evidence suggests that IPH4102 might be an effective treatment for Cutaneous T-Cell Lymphoma?

Research has shown that IPH4102 may effectively treat Sézary syndrome and mycosis fungoides, rare types of skin cancer. One study found that 36.4% of patients responded positively to the treatment. In this trial, participants with Sézary syndrome will receive IPH4102, which uses monoclonal antibodies. Participants with mycosis fungoides, both KIR3DL2 expressing and non-expressing, will also receive IPH4102. Although the response rate for mycosis fungoides was lower, early lab studies have shown promise. Overall, these findings suggest that IPH4102 could be a helpful option for managing these conditions. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced T Cell Lymphoma, specifically Sezary Syndrome and Mycosis fungoides, who have tried at least two other treatments. They must be in good enough health to undergo a biopsy, not have had certain recent treatments or vaccines, no major surgery within the last month, and no active severe infections or other cancers in the past five years.

Inclusion Criteria

MF patients (Cohorts 2 and All comers): Relapsed and/or refractory stage IB, IIA, IIB, III, IV MF; Only for Cohort 2: KIR3DL2 expression in at least one expressing skin lesion based on central evaluation by IHC; Patients should have received at least two prior systemic therapies; Feasibility of obtaining at least one skin biopsy at screening;

I have stage IVA or IVB SS, received at least two treatments, had mogamulizumab, and can have a skin biopsy.

Adequate baseline laboratory data: Hematology: Hemoglobin >9 g/dL, Absolute neutrophil count (ANC) ≥1,500/µL, Platelets ≥100,000/µL, Biochemistry: Bilirubin ≤1.5 X upper limit of normal (ULN) or ≤3 X ULN for patients with Gilbert's disease, Serum creatinine ≤1.5 X ULN, Creatinine clearance ≥30 mL/min, calculated with the Cockcroft & Gault formula, Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5 X ULN; Women of childbearing potential (WOCBP): Premenopausal females who had at least one menstrual cycle in the past 12 months and capable to become pregnant. They must have a negative serum beta-HCG pregnancy test result within seven days from start of treatment; Women of childbearing potential and all men (and their female partners of childbearing potential) who are sexually active must agree to use adequate method of contraception at study entry, during treatment and for at least 9 months (270 days) following the last dose of study drug; Signed informed consent form prior to any protocol-specific procedures

Exclusion Criteria

Patients with evidence of large cell transformation (LCT) based on central histologic evaluation at screening; Receipt of live vaccines within 4 weeks prior to treatment; Central nervous system (CNS) lymphoma involvement; Prior administration of IPH4102; Concurrent enrollment in another clinical trial, unless it is an observational (non - interventional) clinical study or the follow-up period of an interventional study; Autologous stem cell transplantation less than 3 months prior to enrollment; Prior allogenic transplantation; Patients who have undergone major surgery ≤ 4 weeks prior to study entry; Patients with known NCI CTCAE grade 3 or higher active systemic or cutaneous viral, bacterial, or fungal infection; Patients who have Hepatitis B Virus infection determined as HBsAg positive and / or Hepatitis C Virus infection determined as detection of HCV RNA in serum or plasma by a sensitive quantitative molecular method; Known or tested positive for human immunodeficiency virus (HIV); Patients with a history of other malignancies during the past five years apart from the disease subject of this study. The following are exempt from the five-year limit: non-melanoma skin cancer, lymphomatoid papulosis, resected thyroid cancer, biopsy-proven cervical intraepithelial neoplasia, Ductal carcinoma in situ (DCIS) or cervical carcinoma in situ; Pregnant or breastfeeding women; Known clinically significant cardiovascular disease or condition, including: Class III or IV cardiovascular disease according to the New York Heart Association (NYHA) Functional Classification; Any uncontrolled arrhythmia (per the investigator's discretion); Uncontrolled hypertension (per the investigator's discretion). Patients with autoimmune disease on systemic immunosuppressive treatment; Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment and/or comply with study protocol; Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent document.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

IPH4102 is administered every week for 5 weeks, then every 2 weeks for 10 administrations, and then every 4 weeks until disease progression or unacceptable toxicity

Expected average of 2 years

Weekly visits initially, then bi-weekly, and finally monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IPH4102

Trial Overview The study tests IPH4102 alone or combined with chemotherapy on patients with T Cell Lymphoma. It's an open-label phase II trial which means everyone knows what treatment they're getting and it's designed to measure how well the drug works and its safety.

How Is the Trial Designed?

Group I: Cohort All comers: Stage IB-IV Mycosis Fungoides,KIR3DL2 expressing and non-expressing Experimental Treatment 1 Intervention

IPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity.

Group II: Cohort 3: Stage IB-IV Mycosis Fungoides,KIR3DL2 non-expressing (closed) Experimental Treatment 1 Intervention

IPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity.

Group III: Cohort 2: Stage IB-IV Mycosis Fungoides, KIR3DL2 expressing Experimental Treatment 1 Intervention

IPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity.

Group IV: Cohort 1: Relapsed/refractory Sezary Syndrome Experimental Treatment 1 Intervention

IPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Innate Pharma

Lead Sponsor

Trials

29

Recruited

3,100+

Published Research Related to This Trial

Cutaneous T-cell lymphomas, including mycosis fungoides and Sezary syndrome, have distinct clinical behaviors, with mycosis fungoides being more indolent and Sezary syndrome being more aggressive, highlighting the need for tailored treatment approaches.

Current treatments include a variety of skin-directed and systemic therapies, but over 20% of patients with early-stage disease experience progression, indicating a significant need for more effective and durable treatment options, especially for advanced stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of currently available therapies for the mycosis fungoides and Sezary syndrome variants of cutaneous T-cell lymphoma. Whittaker, SJ., Foss, FM.[2007]

Cutaneous T-cell lymphomas (CTCL) have high relapse rates, but survival is generally not significantly affected in low-stage disease, while aggressive subtypes show reduced survival rates.

Recent research has identified new treatment strategies targeting tumor-infiltrating immune cells and the tumor microenvironment, focusing on restoring immunosurveillance and utilizing novel approaches like NF-κB or JAK inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative Treatment Concepts for Cutaneous T-Cell Lymphoma Based on Microenvironment Modulation. Leuchte, K., Schlaak, M., Stadler, R., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03902184

Study Details | NCT03902184 | IPH4102 Alone or in ... This is an open label, multi-cohort, and multi-center phase II study, which evaluates the clinical activity and safety of IPH4102 in Sezary Syndrome and Mycosis ...

2. clfoundation.org clfoundation.org/sites/default/files/2020-12/Bagot,%20Martine%20et%20al.%20The%20Lancet%20Oncology.pdf

IPH4102, a first-in-class anti-KIR3DL2 monoclonal ... A confirmed global overall response was achieved in 16 (36·4% [95% CI 23·8–51·1]) of 44 patients, and of those,. 15 responses were observed in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10585160/

Advances in the treatment of mycoses fungoides and ... The clinically efficacy was modest, with only five patients achieving the primary endpoint of a decrease in modified Severity-Weighted ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119318270

First-in-Human, Multicenter Phase I Study of IPH4102, ... IPH4102 has shown potent efficacy in preclinical models, in particular ex vivo autologous assays using primary CTCL cells. IPH4102 is currently being ...

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00258-X/fulltext

Real-life efficacy of immunotherapy for Sézary syndrome Patients with Sézary syndrome had the best responses to monoclonal antibodies, compared to other cutaneous T-cell lymphoma subtypes, such as mycosis fungoides.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31253572/

IPH4102, a first-in-class anti-KIR3DL2 monoclonal ... IPH4102 is safe and shows encouraging clinical activity in patients with relapsed or refractory cutaneous T-cell lymphoma, particularly those with Sézary ...

7. innate-pharma.com innate-pharma.com/sites/default/files/161026_pr_iph_3wcll_data_iph4102.pdf

PRESS RELEASE - Innate Pharma IPH4102 was granted orphan drug status in the European Union for the treatment of CTCL. About Cutaneous T-Cell Lymphoma (“CTCL”):. CTCL is a heterogeneous ...

8. aacrjournals.org aacrjournals.org/cancerdiscovery/article/9/8/997/41987/A-KIR3DL2-Antibody-Is-Safe-and-Active-in-Cutaneous

A KIR3DL2 Antibody Is Safe and Active in Cutaneous T-cell ... Major Finding: KIR3DL2 antibody IPH4102 exhibits a favorable safety profile and preliminary evidence of efficacy.