Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C/D Melanoma Patients

NCT03567889 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: PH-L19IL2TNF-01/182023-507119-36-00
• Study Type: interventional
• Target: 186
• Locations: 3 countries
• Sites: 37

Brief Summary

The trial aims to evaluate the efficacy of Daromun neoadjuvant treatment followed by surgery and adjuvant therapy to improve in a statistically significant manner the recurrence-free survival (RFS) of Stage IIIB/C/D melanoma patients with respect to the standard of care (surgery and adjuvant therapy).

Conditions

Melanoma Stage IIIC; Melanoma Stage IIID; Melanoma Stage IIIB

Keywords

Melanoma Stage IIIB; Melanoma Stage IIIC; Melanoma Stage IIID

Outcome Measures

Primary Outcomes (1)

• Recurrence Free Survival (RFS)

  Recurrence Free Survival (RFS) in a time-to-event analysis in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus the surgery and adjuvant therapy control group (Arm 2). Analysis will be performed for the "Intention To Treat" population.

  From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first assessed up to 60 months.

Secondary Outcomes (16)

• Overall survival (OS)

  From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first, assessed up to 72 months.

• Recurrence free survival (RFS) as determined by the local investigator

  From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first assessed up to 60 months.

• Event-free survival (EFS)

  From date of randomization until the date of the first event as described above, assessed up to 60 months

• Adverse Events (AE)

  From the inclusion in the study (signature of the informed consent form - ICF) until the first follow-up visit (up to approximately 5 months).

• Immune-related Adverse Events (irAEs)

  From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 60 months).

Other Outcomes (1)

• Local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS)

  From date of randomization until the date of the first recurrence or date of death from any cause, whichever occurs first assessed up to 60 months

Study Arms (2)

Daromun plus Surgery and Adjuvant therapy

EXPERIMENTAL

Arm-1 patients will follow these steps: 1. screening period, 2. 4-week open-label treatment period, 3. surgery within a maximum of 4 weeks, 4. adjuvant therapy.

Drug: Daromun; Procedure: Surgery; Drug: Adjuvant therapy

Surgery and adjuvant therapy

ACTIVE COMPARATOR

Arm-2 patients will follow these steps: 1. Screening period, 2. direct surgery within 4 weeks from randomization, 3. adjuvant therapy.

Procedure: Surgery; Drug: Adjuvant therapy

Interventions

Surgery PROCEDURE

Patients will receive surgery.

Daromun plus Surgery and Adjuvant therapy; Surgery and adjuvant therapy

Adjuvant therapy DRUG

Patients will receive adjuvant therapy at the investigator's discretion following the surgery.

Daromun plus Surgery and Adjuvant therapy; Surgery and adjuvant therapy

Daromun DRUG

Patients will receive intratumoral administrations into injectable cutaneous, subcutaneous, and nodal tumors of Daromun once weekly for up to 4 weeks.

Daromun plus Surgery and Adjuvant therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of clinical stage IIIB, IIIC, and IIID (AJCC 8th edition) locoregional melanoma that is eligible for complete surgical resection of all metastases (surgically resectable).
• Eligible subjects must have measurable disease and must be candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm.
• Prior anti-tumor treatment for the primary melanoma lesion, including surgery and approved adjuvant treatments (e.g., radiotherapy, immune checkpoint inhibitors, BRAF/MEK inhibitors, etc.) is allowed. Before enrollment in the study, a wash-out period of 6 weeks is required and toxicities from prior treatments should be resumed to Grade ≤1.
• Males or females, age ≥ 18 years.
• ECOG Performance Status/WHO Performance Status ≤ 1.
• Life expectancy of \> 24 months.
• Absolute neutrophil count \> 1.5 x 109/L.
• Hemoglobin \> 9.0 g/dL.
• Platelets \> 100 x 109/L.
• Total bilirubin ≤ 30 μmol/L (or ≤ 2.0 mg/dl).
• ALT and AST ≤ 2.5 x the upper limit of normal (ULN).
• Serum creatinine \< 1.5 x ULN.
• LDH serum level ≤ 1.5 x ULN.
• Documented negative test for HIV, HBV and HCV. For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV (i.e. positive anti-HBsAg with not vaccination and/or positive anti-HBcAg Ab), negative serum HBV-DNA is also required.
• All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.03) Grade ≤ 1 unless otherwise specified above.

You may not qualify if:

• Uveal melanoma or mucosal melanoma
• Evidence of distant metastases at screening.
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except: cervical carcinoma in situ, curatively treated basal cell carcinoma, superficial bladder tumors (Ta, Tis \& T1), second primary melanoma in situ or any cancer curatively treated ≥ 5 years prior to study entry.
• Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
• History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
• Inadequately controlled cardiac arrhythmias including atrial fibrillation.
• Heart insufficiency (\> Grade II, New York Heart Association (NYHA) criteria).
• LVEF ≤ 50% and/or abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator.
• Uncontrolled hypertension.
• Ischemic peripheral vascular disease (Grade IIb-IV).
• Severe diabetic retinopathy.
• Active autoimmune disease.
• History of organ allograft or stem cell transplantation.
• Recovery from major trauma including surgery within 4 weeks prior to enrollment.
• Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies or any other constituent of the product.

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (37)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

ACTIVE NOT RECRUITING

UC Irvine Health-Chao Family Comprehensive Cancer Center

Orange, California, 92868-3201, United States

ACTIVE NOT RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Winship Cancer Institute, Emory university

Atlanta, Georgia, 30322, United States

RECRUITING

Rush University Medical Center

Chicago, Illinois, 60612, United States

ACTIVE NOT RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

ACTIVE NOT RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Rutgers Cancer Institute, 195 Little Albany Street

New Brunswick, New Jersey, 08903, United States

RECRUITING

Ambulatory Care Center at NYC Langarone Health

New York, New York, 10016, United States

ACTIVE NOT RECRUITING

Memorial Sloan Kettering Cancer Center - Main Campus

Ney York, New York, 10065, United States

RECRUITING

Duke University Medical Center - Duke Cancer Center

Durham, North Carolina, 27710, United States

RECRUITING

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

St. Luke's Cancer Center, Clinical Trial, 3rd floor, 1600 St. Luke's Blvd.

Easton, Pennsylvania, 18045, United States

ACTIVE NOT RECRUITING

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

RECRUITING

Fox Chase Cancer Center 333 Cottman Avenue

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030-4009, United States

RECRUITING

Huntsman Cancer Institute, University of Utah 2000 Circle of Hope

Salt Lake City, UT, Utah, 84112, United States

RECRUITING

VCU - McGlothlin Medical Education Center

Richmond, Virginia, 980037, United States

RECRUITING

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, 08025, Spain

RECRUITING

Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron

Barcelona, Barcelona, 08035, Spain

RECRUITING

Hospital Clinic Barcelona

Barcelona, Barcelona, 08036, Spain

RECRUITING

El Hospital Universitario De Gran Canaria Dr. Negrin

Las Palmas de Gran Canaria, Canarie, 35010, Spain

RECRUITING

Fundacion Onkologikoa Fundazioa

Donostia / San Sebastian, Gipuzkoa, 20014, Spain

RECRUITING

MD Anderson Cancer Center

Madrid, Madrid, 28033, Spain

ACTIVE NOT RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

RECRUITING

Hospital Universitario Regional de Málaga

Málaga, Malaga, 29010, Spain

RECRUITING

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Murcia, 30120, Spain

RECRUITING

Hospital Universitario Virgen De La Macarena

Seville, Sevilla, 41009, Spain

ACTIVE NOT RECRUITING

Hospital General Universitario de Valencia

Valencia, Spain

RECRUITING

Universitätsspital Basel

Basel, Basel, 4031, Switzerland

ACTIVE NOT RECRUITING

Istituto Oncologico della Svizzera Italiana

Bellinzona, Bellinzona, 6500, Switzerland

RECRUITING

Insel Gruppe AG

Bern, Canton of Bern, 3010, Switzerland

ACTIVE NOT RECRUITING

Hôpitaux Universitaires de Genève

Geneva, Canton of Geneva, 1205, Switzerland

ACTIVE NOT RECRUITING

Kantonsspital St.Gallen

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

RECRUITING

Universitätsspital Zürich (USZ)

Zurich, Canton of Zurich, 8091, Switzerland

RECRUITING

Related Publications (2)

• Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2.

  PMID: 36648215 DERIVED

• Miura JT, Zager JS. Neo-DREAM study investigating Daromun for the treatment of clinical stage IIIB/C melanoma. Future Oncol. 2019 Nov;15(32):3665-3674. doi: 10.2217/fon-2019-0433. Epub 2019 Sep 20.

  PMID: 31538818 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

daromun; Surgical Procedures, Operative; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy

Central Study Contacts

Sheila Dakhel, PhD

CONTACT

+41 (0) 43 544 88 02; sheila.dakhel@philogen.com

Concetta Aulicino

CONTACT

+39 0577 17 816; regulatory@philogen.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Total patients: approximately 186. Daromun plus surgery and adjuvant therapy treatment group (Arm 1): 93 evaluable patients. Surgery and adjuvant therapy (Arm 2): 93 evaluable patients. Patients enrolled will be randomized to the two different arms of the study.

Study Record Dates

• First Submitted: May 18, 2018
• First Posted: June 26, 2018
• Study Start: September 20, 2018
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2031
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (12); CH (6); US (19)