L19IL2/L19TNF in patients with non-melanoma skin cancer.

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 Dec 2024 → 17 Oct 2025

Decision date (initial)

2024-11-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518530-92-00

EudraCT number

2020-003299-42

ClinicalTrials.gov

NCT04362722

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Confirmed Best Overall Response Rate (BORR) [Complete Response (CR) + Partial Response (PR)] for BCC tumor type measured according to RECIST v1.1 criteria. Confirmation of CR requires histopathological analysis of exeresis specimens for lesions removed by surgery or of biopsies in all other cases.

Secondary objectives 2

1. Efficacy of L19IL2/L19TNF-treated lesions measured as: o Disease Control Rate (DCR) [Complete Response (CR) + Partial Response (PR) + Stable Disease (SD)] for each tumor type measured according to RECIST v1.1 criteria. o Progression-Free Survival (PFS), assessed separately in patients who are not resected after curative intention and in patients who undergo secondary surgery (neoadjuvant intention), whatever the RECIST response to treatment, taking into account appearance of new lesions and occurrence of metastases, etc. o Pathological Response for each tumor type in surgical specimens from tumors which are resected after treatment, or in biopsy for the other types.
2. Safety of intratumoral administration of L19IL2/L19TNF.

Conditions and MedDRA coding

Patients with high-risk, locally advanced (non-metastatic, node negative, single or multifocal), Basal Cell Carcinoma (BCC) or cutaneous Squamous Cell Carcinoma (cSCC) amenable to intratumoral injection, not eligible to surgery or radiation therapy according to the evaluation of a local interdisciplinary tumor board or who refuse surgery or radiation therapy and for whom a histological evaluation is available according to international guidelines.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Patients with high-risk, locally advanced (non-metastatic, node negative, single or multifocal), basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC) amenable to intratumoral injection, not eligible to surgery or radiation therapy according to the evaluation of a local interdisciplinary tumor board or who refuse surgery or radiation therapy and for whom an histological evaluation is available according to international guidelines. Eligible patients are those as defined by the European Association of Dermato-Oncology (EADO) operational staging system (stages IIa to IIIb) [1] for BCC and by EADO/EORTC (European Organization for Research and Treatment of Cancer) interdisciplinary guidelines [1] for cSCC.
2. 2. Patients with injectable and measurable regional cutaneous or subcutaneous in-transit or satellite metastasis but without regional nodal involvement are also eligible.
3. 3. Male or female patients, age 18 - 100 years.
4. 4. ECOG Performance Status/WHO Performance Status ≤ 1.
5. 5. Hemoglobin > 10.0 g/dL
6. 6. Platelets > 100 x 109/L.
7. 7. ALT and AST, GGT and Lipase ≤ 1.5 x the upper limit of normal (ULN).
8. 8. Serum creatinine < 1.5 x ULNAn age-calibrated definition of CKD has been proposed to distinguish age-related from disease-related changes in eGFR. For patients younger than 40 years, CKD is defined by eGFR below 75 mL/min/1.73m2. For patients with ages between 40 and 65 years, CKD is defined by 60 mL/min/1.73m2. For subjects older than 65 years without albuminuria or proteinuria, CKD is defined by eGFR below 45 mL/min/1.73m2.
9. 9. 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 v. 5.0) Grade ≤ 1 unless otherwise specified.
10. 10. Women Of Childbearing Potential (WOCBP) must have negative pregnancy test results at screening. WOCBP must be using, from screening to three months following the last study drug administration, highly effective contraception methods, as 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, vasectomised partner.
11. 11. 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.
12. 12. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion criteria 21

1. 1. Previous or concurrent cancer type that is distinct from the cancers being evaluated in this study, except any cancer curatively treated more than 2 years prior to study entry.
2. 2. Topical or systemic chemotherapy, immunotherapy or radiation therapy on the tumor sites in the 4 weeks prior to study drug administration.
3. 3. Patients with node positive BCC/cSCC who are candidate to SHH inhibitor or checkpoint inhibitor therapy.
4. 4. Presence of active severe bacterial or viral infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study. In particular a documented test for HIV, HBV and HCV excluding active infection is needed.
5. 5. History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris, of inadequately treated cardiac arrhythmias and heart insufficiency (any grade, New York Heart Association (NYHA) criteria).
6. 6. Any abnormalities observed during baseline ECG investigations that are considered as clinically significant by the investigator.
7. 7. Known arterial aneurysms.
8. 8. INR > 3.
9. 9. Uncontrolled hypertension.
10. 10. Known uncontrolled coagulopathy or bleeding disorder.
11. 11. Known hepatic cirrhosis or severe pre-existing hepatic impairment.
12. 12. Moderate to severe respiratory failure.
13. 13. Active autoimmune disease.
14. 14. Patient requires or is taking systemic corticosteroids (>5 mg/day) or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions and asthma/COPD is not considered an exclusion criterion.
15. 15. Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies.
16. 16. Pregnancy or breast-feeding.
17. 17. Ischemic peripheral vascular disease (Grade IIb-IV).
18. 18. Severe diabetic retinopathy.
19. 19. Recovery from major trauma including surgery within 4 weeks prior to enrollment.
20. 20. Solid organ transplant recipient or patient with iatrogenic or pathologic severe immune suppression.
21. 21. Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy of L19IL2/L19TNF measured as: Confirmed Best Overall Response Rate (BORR) [Complete Response (CR) + Partial Response (PR)] for BCC tumor type measured according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Confirmation of CR requires histopathological analysis of exeresis specimens for lesions removed by surgery or of biopsies in all other cases.

Secondary endpoints 2

1. Efficacy of L19IL2/L19TNF measured as: o Disease Control Rate (DCR) [Complete Response (CR) + Partial Response (PR) + Stable Disease (SD)] for each tumor type measured according to RECIST v1.1 criteria. o Progression-Free Survival (PFS), assessed separately in patients who are not resected after curative intention and in patients who undergo secondary surgery (neoadjuvant intention), whatever the RECIST response to treatment, taking into account appearance of new lesions and occurrence of metast
2. Safety of intratumoral administration of L19IL2/L19TNF.

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

Lisa Nadal

Public contact point

Organisation

Philogen S.p.A.

Contact name

Lisa Nadal

Third parties 2

Locations

2 EU/EEA countries · 9 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 11 files

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

Application history

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