Study of the efficacy of intratumoral injections of L19IL2 + L19TNF followed by surgery to prevent or retard appearance of new metastases

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Philogen S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 May 2022 → ongoing

Decision date (initial)

2026-02-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Philogen S.p.A.

External identifiers

EU CT number

2023-507119-36-00

EudraCT number

2021-003064-27

ClinicalTrials.gov

NCT03567889

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Safety, Therapy

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 melanoma patients with respect to the standard of care (surgery and adjuvant therapy).

Secondary objectives 1

1. Secondary objective of the study is to demonstrate that a neoadjuvant Daromun treatment followed by surgery and adjuvant therapy improves in a statistically significant manner the overall survival (OS) of patients with resectable Stage IIIB or C melanoma patients with respect to the standard of care (surgery and adjuvant therapy). Other secondary objectives include improvement of RFS as determined by the local investigator and, for patients included in Arm 1 only, pathological responses (i.e., p Complete Response, p near-Complete Response, p Partial Response, p Non Response) assessed at time of surgical resection, as well as demonstration of safety and tolerability of the Daromun treatment

Conditions and MedDRA coding

Malignant melanoma of the skin in patients with locally advanced and fully resectable melanoma with/without prior therapy and presence of injectable cutaneous and/or subcutaneous or nodal lesions

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Diagnosis of clinical stage IIIB and IIIC (AJCC v7) metastatic melanoma, 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. Males or females, age ≥ 18 years
4. ECOG Performance Status/WHO Performance Status ≤ 1.
5. Life expectancy of > 24 months
6. Absolute neutrophil count > 1.5 x 109/L
7. Hemoglobin > 9.0 g/dL
8. Platelets > 100 x 109/L
9. Total bilirubin ≤ 30 μmol/L (or ≤ 2.0 mg/dl)
10. ALT and AST ≤ 2.5 x the upper limit of normal (ULN)
11. Serum creatinine < 1.5 x ULN
12. LDH serum level ≤ 1.5 x ULN
13. 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 negative serum HBV-DNA is also required
14. 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
15. 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)
16. 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
17. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study
18. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures

Exclusion criteria 22

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, 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. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint of the study is 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

Secondary endpoints 1

1. The key secondary objective of the study is Overall Survival (OS) with the aim to demonstrate the statistical superiority of Daromun plus surgery and adjuvant therapy with respect to surgery and adjuvant therapy. Other secondary objectives include improvement of RFS as determined by the local investigator, local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) and, for patients in Arm 1 only, pathological responses

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Philogen S.p.A.

Sponsor organisation

Philogen S.p.A.

Address

Piazza La Lizza 7

City

Siena

Postcode

53100

Country

Italy

Scientific contact point

Organisation

Philogen S.p.A.

Contact name

Sheila Dakhel

Public contact point

Organisation

Philogen S.p.A.

Contact name

Sheila Dakhel

Third parties 2

Locations

4 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications