A study to investigate the efficacy of Daromun (L19IL2 + L19TNF) before cancer surgery followed by standard therapy (surgery with subsequent supportive therapy) compared to standard therapy in patients with stage IIIB/C melanoma.

Spain, Switzerland, United States (ICTRP)

Identifiant de l'essai ICTRP
NCT03567889 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
An Open-Label, Randomized, Controlled Multi-Center Study of The Efficacy of Daromun (L19IL2 + L19TNF) Neoadjuvant Intratumoral Treatment Followed by Surgery and Adjuvant Therapy Versus Surgery and Adjuvant Therapy in Clinical Stage IIIB/C/D Melanoma Patients (BASEC)

Titre académique
An Open-Label, Randomized, Controlled Multi-Center Study of The Efficacy of Daromun (L19IL2 + L19TNF) Neoadjuvant Intratumoral Treatment Followed by Surgery and Adjuvant Therapy Versus Surgery and Adjuvant Therapy in Clinical Stage IIIB/C/D Melanoma Patients (ICTRP)

Titre public
Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C/D Melanoma Patients (ICTRP)

Maladie en cours d'investigation
Melanoma Stage IIIBMelanoma Stage IIICMelanoma Stage IIID (ICTRP)

Intervention étudiée
Drug: DaromunProcedure: SurgeryDrug: Adjuvant therapy (ICTRP)

Type d'essai
Interventional (ICTRP)

Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Critères d'inclusion/exclusion
Inclusion Criteria:

1. 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).

2. 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.

3. 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.

4. Males or females, age = 18 years.

5. ECOG Performance Status/WHO Performance Status = 1.

6. Life expectancy of > 24 months.

7. Absolute neutrophil count > 1.5 x 109/L.

8. Hemoglobin > 9.0 g/dL.

9. Platelets > 100 x 109/L.

10. Total bilirubin = 30 mol/L (or = 2.0 mg/dl).

11. ALT and AST = 2.5 x the upper limit of normal (ULN).

12. Serum creatinine < 1.5 x ULN.

13. LDH serum level = 1.5 x ULN.

14. 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.

15. 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.

16. All women of childbearing potential (WOCBP) must have negative pregnancy test
results at the screening. WOCBP must be using, from the screening to three months
following the last study drug administration, highly effective contraception
methods. WOCBP and effective contraception methods are defined by the
"Recommendations for contraception and pregnancy testing in clinical trials" issued
by the Head of Medicine Agencies' Clinical Trial Facilitation Group and which
include, for instance, progesterone-only or combined (estrogen- and
progesterone-containing) hormonal contraception associated with inhibition of
ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral
tubal occlusion, vasectomized partner or sexual abstinence. Pregnancy test will be
repeated at the safety visit (only WOCBP and only for patients in Arm 1).

17. Male patients with WOCBP partners must agree to use simultaneously two acceptable
methods of contraception (i.e. spermicidal gel plus condom) from the screening to
three months following the last study drug administration.

18. Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the study.

19. Willingness and ability to comply with the scheduled visits, treatment plan,
laboratory tests and other study procedures.

Exclusion Criteria

1. Uveal melanoma or mucosal melanoma

2. Evidence of distant metastases at screening.

3. 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.

4. 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.

5. History within the last year of acute or subacute coronary syndromes including
myocardial infarction, unstable or severe stable angina pectoris.

6. Inadequately controlled cardiac arrhythmias including atrial fibrillation.

7. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).

8. LVEF = 50% and/or abnormalities observed during baseline ECG and Echocardiogram
investigations that are considered as clinically significant by the investigator.

9. Uncontrolled hypertension.

10. Ischemic peripheral vascular disease (Grade IIb-IV).

11. Severe diabetic retinopathy.

12. Active autoimmune disease.

13. History of organ allograft or stem cell transplantation.

14. Recovery from major trauma including surgery within 4 weeks prior to enrollment.

15. Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies or
any other constituent of the product.

16. Breast feeding female.

17. Anti-tumor therapy (except small surgery) within 4 weeks before enrollment.

18. Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6
weeks before enrollment.

19. Planned administration of growth factors or immunomodulatory agents within 7 days
before enrollment.

20. Patient requiring or taking corticosteroids or other immunosuppressant drugs on a
long-term basis will be evaluated case by case with the Sponsor for
inclusion/exclusion in the study. Limited use of corticosteroids to treat or prevent
acute hypersensitivity reactions is not considered an exclusion criteria.

21. Any conditions that in the opinion of the investigator could hamper compliance with
the study protocol.

22. Previous enrolment and randomization in the same study. (ICTRP)

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Critères d'évaluation principaux et secondaires
Recurrence Free Survival (RFS) (ICTRP)

Overall survival (OS);Recurrence free survival (RFS) as determined by the local investigator;Event-free survival (EFS);Adverse Events (AE);Immune-related Adverse Events (irAEs);Drug-Induced Liver Injury (DILI);Adverse Events of Special Interest (AESI);Haematological/chemical Laboratory Abnormalities;Electrocardiogram (ECG) and echocardiogram (ECHO) abnormalities;Physical examination;Concomitant medication;Human anti-fusion protein antibodies (HAFA);Vital signs (blood pressure);Vital signals (heart rate);Vital signals (body temperature);Pathological responses (ICTRP)

Date d'enregistrement
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Inclusion du premier participant
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Sponsors secondaires
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Contacts supplémentaires
Niccolò Ravenni, PhD, regulatory@philogen.com, +39057717816 (ICTRP)

ID secondaires
2023-507119-36-00, PH-L19IL2TNF-01/18 (ICTRP)

Résultats-Données individuelles des participants
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Informations complémentaires sur l'essai
https://clinicaltrials.gov/study/NCT03567889 (ICTRP)