L19IL2/L19TNF for Skin Cancer

Overseen By Concetta Aulicino

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Philogen S.p.A.

Must not be taking: Chemotherapy, Immunotherapy, Steroids, others

Disqualifiers: Concomitant malignancies, Visceral metastasis, Severe infections, 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: 12

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with locally advanced Cutaneous Squamous Cell Carcinoma (cSCC) that has not responded to or cannot be treated with certain immune therapies. The treatment involves injecting a combination of two experimental substances, L19IL2 and L19TNF, directly into the cancerous lesions to assess tumor shrinkage and safety. Individuals with cSCC who have injectable tumors and have encountered issues with standard immune treatments might be suitable for this trial. Participants will receive injections once a week for up to four weeks, with their progress monitored over an extended period. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on current topical or systemic chemotherapy or immunotherapy, and you should not be on chronic systemic steroid therapy exceeding 10 mg daily of prednisone equivalent. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that L19IL2/L19TNF is likely to be safe for humans?

Research has shown that using L19IL2 and L19TNF together has been safe in earlier studies. For instance, a study with patients who had cutaneous squamous cell carcinoma (a type of skin cancer) found that the treatment helped shrink tumors without causing major safety issues. Another study with patients who had melanoma (another type of skin cancer) also found that the treatment was well-tolerated.

While new treatments always come with some risks, these results suggest that L19IL2/L19TNF is generally safe for people. Those with concerns about side effects should talk to the clinical trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for skin cancer?

Unlike the standard treatments for skin cancer, which often include surgery, radiation, or systemic therapies like chemotherapy, L19IL2/L19TNF offers a novel approach by directly targeting tumor sites. This treatment is unique because it involves a mixture of two cytokines, L19IL2 and L19TNF, which are delivered directly into the skin and subcutaneous tumors through intratumoral injections. Researchers are excited about this treatment because it targets tumors more precisely, potentially boosting the body's immune response directly where it's needed without affecting the entire body. This localized approach could lead to fewer side effects and a more effective attack on cancer cells, offering hope for more efficient skin cancer management.

What evidence suggests that L19IL2/L19TNF might be an effective treatment for skin cancer?

Research has shown that L19IL2/L19TNF, the treatment under study in this trial, may help treat skin cancer, particularly types like Cutaneous Squamous Cell Carcinoma (lacSCC). In some studies, patients with difficult-to-treat non-melanoma skin cancer showed early positive responses and experienced few side effects after receiving this treatment. When combined with other treatments, such as anti-PD1 therapy, patients demonstrated noticeable improvement in response and longer periods without disease progression. These findings suggest that L19IL2/L19TNF could be a viable option for those who haven't responded well to other treatments. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-100 with advanced skin cancer (cSCC) that's worsened or doesn't respond to immune checkpoint inhibitors. They must have at least one tumor on the skin or just below it that can be injected, and their overall health should allow basic activity. Blood counts and liver enzymes need to be within certain limits.

Inclusion Criteria

My hemoglobin level is above 10.0 g/dL.

My platelet count is above 100 x 10^9/L.

My liver enzymes and lipase levels are within normal limits.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intratumoral administrations of L19IL2/L19TNF once weekly for up to 4 weeks

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with tumor assessments every 8 weeks for the first year and every 12 weeks for the second and third years

160 weeks

Regular visits every 8-12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• L19IL2/L19TNF

Trial Overview

The study tests a treatment where L19IL2/L19TNF is directly injected into the tumors once a week for up to four weeks, possibly repeating if there's improvement or no worsening of disease. The main goal is to see how well this works and its safety over a period of up to 160 weeks.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

the patients will receive multiple intratumoral administrations of a mixture of L19IL2 and L19TNF to all injectable cutaneous and subcutaneous lesions once weekly for up to 4 weeks.

Who Is Running the Clinical Trial?

Philogen S.p.A.

Lead Sponsor

Trials

42

Recruited

2,400+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05329792

NCT05329792 | L19IL2/L19TNF in Skin Cancer Patients

In the study, 70 patients will be enrolled and treated with a mixture of L19IL2 and L19TNF once weekly for 4 consecutive weeks.

2.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-08754

Study of the Efficacy of Intratumoral L19IL2 or L19TNF or ...

The trial aims to evaluate the efficacy of single agent L19IL2, single agent L19TNF, and combination L19IL2+L19TNF given concurrently with anti-PD1 therapy.

3.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(23)03109-5/fulltext

1138P Intralesional administration of L19IL2/L19TNF in ...

Intralesional administration of L19IL2/L19TNF in difficult-to-treat non-melanoma skin cancer shows a favorable safety profile and preliminary clinical activity.

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS9617

Intralesional administration of L19IL2/L19TNF in high-risk ...

The first part of the trial has been completed with 28 laBCC pts and 12 lacSCC pts evaluable for safety and efficacy. The pre-specified activity ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11028321/

A phase II study of the L19IL2 immunocytokine in combination ...

Analyses of efficacy results show a statistically significant benefit in terms of overall response rate and median progression-free survival for ...

6.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(25)04842-2/fulltext

LBA60 Favorable activity and safety of intralesional L19IL2 ...

Using BCC-adapted RECIST-like criteria as exploratory endpoint, the ORR was 57.8%. In the lacSCC cohort, 21 patients were evaluable with BORR of 41.1%. Daromun ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07227350

Study Details | NCT07227350 | L19IL2 or L19TNF or ...

L19IL2 or L19TNF or L19IL2/L19TNF will be administered to eligible patients under the supervision of the investigator or identified sub-investigator(s).

8.

mycancergenome.org

mycancergenome.org/content/clinical_trials/NCT04362722/

Clinical Trial: NCT04362722

Favorable tumor responses following intralesional treatment with L19IL2/L19TNF have been observed in patients with injectable melanoma lesions ...