Neoadjuvant Daromun + Surgery for Melanoma

(NeoDREAM Trial)

Recruiting at 40 trial locations

Overseen By Giuliano Elia, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Philogen S.p.A.

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Uveal melanoma, Distant metastases, Active infections, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

186 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Daromun (also known as Nidlegy) before surgery for individuals with Stage IIIB/C melanoma, a type of skin cancer. The goal is to determine if this approach can prevent cancer recurrence more effectively than the standard treatment, which involves surgery followed by additional therapy. The trial includes two groups: one will receive Daromun before surgery, and the other will proceed directly to surgery. It suits those with melanoma that can be surgically removed and have a visible tumor of at least 10 mm that can be injected. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you do not take corticosteroids or other immunosuppressant drugs on a long-term basis. If you are on these medications, you may need to stop them before joining the trial.

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

Research has shown that Daromun, when used before melanoma surgery, is mostly safe for patients. Studies have found that most side effects are mild and occur at the application site. About 12.7% of patients experienced more serious side effects, though these were uncommon. No severe immune-related side effects were reported, indicating that Daromun is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for melanoma?

Most treatments for melanoma focus on surgery followed by adjuvant therapies like chemotherapy or radiation to eliminate any remaining cancer cells. But Daromun is unique because it combines two cytokines, IL-2 and TNF, in a single formulation designed to stimulate the immune system directly against the tumor. Researchers are excited about Daromun because it targets melanoma cells more precisely and may enhance the body's natural immune response, potentially improving the effectiveness of surgery and reducing the chance of cancer recurrence.

What evidence suggests that Daromun plus surgery and adjuvant therapy could be effective for melanoma?

This trial will compare the use of Daromun plus surgery and adjuvant therapy with surgery and adjuvant therapy alone. Research has shown that using Daromun before surgery can help people with locally advanced melanoma live longer without cancer recurrence. In one study, patients who received Daromun had a 41% lower chance of cancer returning or dying compared to those who only had surgery. Another study found that Daromun also reduced the risk of cancer spreading to other parts of the body. These findings suggest that Daromun can effectively improve outcomes in melanoma patients. ^{1 3 6 7 8}

Who Is on the Research Team?

Jonathan Zager, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Stage IIIB/C melanoma that can be surgically removed. They must have a life expectancy over 24 months, good performance status, and normal organ function tests. Women of childbearing age must test negative for pregnancy and use effective contraception. Exclusions include other cancer types, uncontrolled diseases, recent major trauma or surgery, breastfeeding women, certain drug treatments within specific timeframes before enrollment.

Inclusion Criteria

You are expected to live for more than 24 months.

I have tested negative for HIV, Hepatitis B, and Hepatitis C.

Your total bilirubin level in the blood needs to be below a certain number.

Exclusion Criteria

My cancer has spread to distant parts of my body.

I haven't had any cancer treatment except minor surgery in the last 4 weeks.

I have had cancer before, but it was a different type or treated over 5 years ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants in Arm 1 receive Daromun neoadjuvant treatment for 4 weeks, followed by surgery within a maximum of another 4 weeks and adjuvant therapy. Arm 2 receives direct surgery within 4 weeks from randomization, followed by adjuvant therapy.

8 weeks

Follow-up

Participants are monitored for recurrence-free survival and overall survival, with follow-up assessments up to five years after randomization.

60 months

Extended Follow-up

Survival information is collected for an additional year after the initial follow-up period.

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Adjuvant therapy
• Daromun
• Surgery

Trial Overview The study is testing the effectiveness of Daromun as a pre-surgery (neoadjuvant) treatment followed by surgery and additional therapy to see if it helps patients with Stage IIIB/C melanoma live longer without their cancer returning compared to just having surgery and additional therapy.

How Is the Trial Designed?

Group I: Daromun plus Surgery and Adjuvant therapy (Arm 1) Experimental Treatment 3 Interventions

Two-weeks screening period and a 4-weeks open-label treatment period, followed by surgery within a maximum of another 4 weeks and adjuvant therapy (Arm 1).

Group II: Surgery and adjuvant therapy (Arm 2) Active Control 2 Interventions

Patients in the control arm (Arm 2) will receive direct surgery within 4 weeks from randomization, followed by adjuvant therapy.

Daromun is already approved in European Union for the following indications:

Approved in European Union as Nidlegy for:

• Locally advanced, fully resectable melanoma

Who Is Running the Clinical Trial?

Philogen S.p.A.

Lead Sponsor

Trials

42

Recruited

2,400+

Published Research Related to This Trial

Neoadjuvant therapies, including targeted BRAF/MEK inhibition and immune checkpoint blockade, are showing promise in treating malignant melanoma, particularly for patients with clinically node-positive and oligometastatic disease, which traditionally required surgical resection.

The review highlights the importance of ongoing clinical trials and future research directions, such as biomarker development and novel treatment regimens, to optimize neoadjuvant therapy outcomes for melanoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant therapy for melanoma: new and evolving concepts. Erstad, DJ., Witt, RG., Wargo, JA.[2023]

Neoadjuvant therapy in melanoma is being actively researched, with numerous trials showing that it can improve outcomes for high-risk patients who have a significant chance of relapse after surgery.

Current treatments like anti-PD-1 immunotherapy and BRAF/MEK-targeted therapy have been effective in improving relapse-free and overall survival, but many patients still face relapses and treatment-related side effects, highlighting the need for ongoing research into new therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Neoadjuvant Therapy in Melanoma. Kelly, ZR., Gorantla, VC., Davar, D.[2021]

A nationwide survey of 120 hospitals in Italy revealed that many centers do not follow international protocols for excision margins and sentinel lymph node procedures in melanoma treatment, with 21% using 1 cm margins for excisional biopsies.

The study highlights the need for standardized treatment protocols to ensure proper excision margins and sentinel lymph node procedures, as improper techniques could affect the accuracy of melanoma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical management of suspicious melanocytic lesions in Italy. De Giorgi, V., Ascierto, P., Bono, R., et al.[2013]

Inguinal lymph node dissections for metastatic melanoma can lead to significant complications such as infection and lymphedema, but strategies like optimizing preoperative assessments and postoperative care can help reduce these risks.

There is ongoing debate about the best surgical techniques, including whether to perform pelvic lymphadenectomy and how to preserve certain veins and muscles, highlighting the need for further research to clarify these practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limiting the morbidity of inguinal lymphadenectomy for metastatic melanoma. Sarnaik, AA., Puleo, CA., Zager, JS., et al.[2017]

Recent trials indicate that completion lymph node dissection does not improve survival for patients with sentinel node-positive melanoma, suggesting that observation may be more beneficial, especially for those with larger metastases.

Adjuvant therapies, including immunotherapy with ipilimumab and targeted therapy with dabrafenib and trametinib, have shown improved survival outcomes, leading to a shift in clinical guidelines and a more personalized approach to treatment for stage III melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The extent of surgery for stage III melanoma: how much is appropriate? Franke, V., van Akkooi, ACJ.[2020]

Neoadjuvant systemic therapy (NAST) for high-risk, resectable metastatic melanoma is gaining traction, with a focus on the surgical oncologist's role in managing treatment and surgical outcomes.

The International Neoadjuvant Melanoma Consortium aims to standardize NAST trials to establish its safety and efficacy, potentially making it a standard care approach and enabling more personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC). van Akkooi, ACJ., Hieken, TJ., Burton, EM., et al.[2023]

Neoadjuvant therapy for stage III melanoma is being explored as a promising approach to improve surgical outcomes and overall survival, especially for high-risk patients who typically have poor results with upfront surgery.

The establishment of the International Neoadjuvant Melanoma Consortium aims to standardize trial designs and analyses, which will enhance data organization for regulatory review and support future research in melanoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant systemic therapy in melanoma: recommendations of the International Neoadjuvant Melanoma Consortium. Amaria, RN., Menzies, AM., Burton, EM., et al.[2020]

In the phase III CheckMate 238 trial, 67.7% of patients receiving nivolumab experienced treatment-related adverse events (TRAEs), with the most common being pruritus and diarrhea, primarily occurring within the first 3 months of treatment.

Despite the high incidence of TRAEs, there was no significant association found between these adverse events and recurrence-free survival (RFS), indicating that the safety profile of nivolumab remains consistent and does not negatively impact long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. Mandala, M., Larkin, J., Ascierto, PA., et al.[2022]

The modified ilioinguinal node dissection technique, which preserves the saphenous vein and femoral sheath, resulted in a low postoperative edema rate of only 5% among 19 patients, indicating improved safety compared to standard procedures.

At 40 months, the disease-free survival rates were 66% for patients with N1 disease and 26% for those with N2, M1 metastases, suggesting that the modified approach does not compromise survival outcomes while potentially reducing costs and morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified ilioinguinal node dissection for metastatic melanoma. Pearlman, NW., Robinson, WA., Dreiling, LK., et al.[2019]

Surgical management of melanoma has evolved significantly, with a focus on local control of the primary tumor and the introduction of lymphatic mapping and sentinel lymph node identification, which helps select patients for further treatment.

Surgery remains important not only for controlling the primary tumor but also for palliative care in selected Stage IV melanoma patients with isolated systemic metastases and good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The role of surgery in the treatment of cutaneous melanoma]. Guggenheim, M., Dummer, R., Giovanoli, P.[2011]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00829-4/fulltext

Neoadjuvant intralesional targeted immunocytokines ... Neoadjuvant intralesional daromun in pretreated locally advanced melanoma results in 41% reduction in relapse or death risk. •. The risk ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA9501

Phase 3 study (PIVOTAL) of neoadjuvant intralesional ... The safety profile of Daromun was characterized mostly by low-grade, local adverse events (14% grade 3 TEAEs). Systemic AEs were limited and of ...

3. onclive.com onclive.com/view/neoadjuvant-daromun-yields-improved-recurrence-free-survival-in-locally-advanced-melanoma

Neoadjuvant Daromun Yields Improved Recurrence-Free ... Neoadjuvant daromun significantly improved RFS and reduced distant metastasis risk in locally advanced melanoma compared to upfront surgery. The ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0923753425008294

Neoadjuvant Intralesional Targeted Immunocytokines ... Neoadjuvant daromun resulted in a significantly longer RFS than upfront surgery in patients with locally advanced melanoma. TRAEs were transient ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40633690/

Neoadjuvant intralesional targeted immunocytokines ... Conclusions: Neoadjuvant daromun resulted in a significantly longer RFS than upfront surgery in patients with locally advanced melanoma. TRAEs were transient ...

6. philogen.com philogen.com/philogen/wp-content/uploads/2024/05/240529_Press_release_PIVOTAL_ASCO_FINAL.pdf

Results of the Phase III PIVOTAL trial of Nidlegy in ... The safety profile of Nidlegy was characterized mostly by low-grade, local adverse events (12.7% grade 3 TEAEs). No. Grade 3-4 immune-related ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0923753425008294

Neoadjuvant intralesional targeted immunocytokines ... Neoadjuvant intralesional daromun in pretreated locally advanced melanoma results in 41% reduction in relapse or death risk. •. The risk reduction of distant ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)03709-1/fulltext

1095TiP Daromun, a dermato-oncology drug in ... Daromun (Nidlegy®) is an immuno-oncology drug in clinical development for the treatment of melanoma and non-melanoma skin cancers (NMSC).