L19IL2/L19TNF in Skin Cancer Patients

NCT05329792 | Unknown Phase 2 DMC

• 1 other identifier: PH-L19IL2TNFBASK-04/21
• Study Type: interventional
• Target: 70
• Locations: 3 countries
• Sites: 14

Brief Summary

Phase II, open label, multicentric, proof-of-principle basket trial in patients with malignant tumors of the skin amenable to intratumoral injection, and in a curative or neoadjuvant or palliative intention.

Conditions

BCC - Basal Cell Carcinoma; SCC - Squamous Cell Carcinoma; Merkel Cell Carcinoma; Keratoacanthoma of Skin; Malignant Adnexal Tumors of the Skin (MATS); Tumors From Cutaneous T-cell Lymphoma (CTCL); Kaposi Sarcoma

Outcome Measures

Primary Outcomes (1)

• Confirmed best overall response rate (BORR)

  Efficacy of L19IL2/L19TNF measured as Confirmed best overall response rate (BORR) \[Complete Response (CR) + Partial Response (PR)\] for each 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.

  Visit will be performed at week 12

Secondary Outcomes (6)

• Disease control rate (DCR)

  Visits will be performed at week 12, week 20, week 28, week 36, week 44 and week 52

• Local PFS (LPFS)

  Visits will be performed at week 12, week 20, week 28, week 36, week 44 and week 52

• Progression-free survival (PFS)

  Visits will be performed at week 12, week 20, week 28, week 36, week 44 and week 52

• Adverse Events (AE)

  From the inclusion in the study (signature of the informed consent form - ICF) until the end of the trial (week 52).

• Serious Adverse Event (SAEs)

  From the inclusion in the study (signature of the informed consent form - ICF) until the end of the trial (week 52).

Study Arms (1)

Treatment arm with L19IL2 /L19TNF

EXPERIMENTAL

70 patients will be enrolled and treated with a mixture of L19IL2 and L19TNF once weekly for 4 consecutive weeks. The total dose/volume will be distributed among the target lesions defined at screening via single or multiple intralesional injections, according to lesions' size and number.

Drug: L19IL2/L19TNF

Interventions

L19IL2/L19TNF DRUG

Patients will be treated with a mixture of L19IL2 and L19TNF once weekly for 4 consecutive weeks

Also known as: bifikafusp alfa/onfekafusp alfa

Treatment arm with L19IL2 /L19TNF

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient participation to the present study is subjected to the positive evaluation of a local interdisciplinary tumor board, in the context of available treatment alternatives. Whatever the tumor (list of eligible tumors below) the local interdisciplinary tumor board has to consider that a local response to injection of L19IL2/L19TNF may be of benefit for the patient, in the context of this tumor and available therapeutic opportunities, benefit defined by any of the following objectives: (1) to avoid surgery considered difficult or mutilating or (2) as a neoadjuvant treatment with the objective to permit surgery considered initially impossible, or to facilitate surgery considered difficult or mutilating, or to secure surgery considered of uncertain effect or (3) as a salvage treatment to control a tumor proved resistant to treatment alternatives or (4) as a palliative treatment improving patient comfort.
• Patient must have at least one skin tumor that is amenable to intratumoral injection.
• All tumors must be histologically confirmed before treatment.
• Patients with skin tumors eligible to the present study include:
• BCC patients with difficult-to-treat lesions: as defined by EADO operational staging system (stages IIa to IIIb) \[1\]. Patients must either (i) have already received, or (ii) have progressed after, or (iii) be resistant to, or (iv) not be candidate to all possible alternative treatments, including notably use or re-use of surgery, radiotherapy, hedgehog inhibitors.
• Non-metastatic cSCC patients:
• either advanced SCC for which a simple surgical excision is difficult or impossible, or
• common SCC at high risk of recurrence, for which surgery alone is deemed uncertain by the tumor board, according to EADO /EORTC interdisciplinary guidelines \[2\]. Patients must either (i) have already received, or (ii) have progressed after, or (iii) be resistant to, or (iv) not be candidate to all possible alternative treatments, including notably use or re-use of surgery, radiotherapy, cetuximab and/or other anti-PD1 checkpoint inhibitors.
• KA: particularly when surgical excision is considered as too much mutilating for this type of tumor
• MCC: particularly when either primary tumor is considered unresectable, or skin metastases or local relapse are primarily or secondarily resistant to anti-PD1 (progress under anti-PD1). Patients must either (i) have already received, or (ii) have progressed after, or (iii) be resistant to, or (iv) not be candidate to all possible alternative treatments, including notably use or re-use of surgery, radiotherapy, and/or any anti-PD1 checkpoint inhibitors.
• MATS: Advanced or refractory MATS.
• Subjects must have radiographically or clinically measurable disease, defined as at least one injectable lesion that is ≥ 10 mm in diameter in at least 1 dimension, or an aggregate of injectable lesions that measures ≥ 10 mm in diameter in at least 1 dimension.
• Subjects must be able and willing to undergo serial biopsies of injected lesion(s) and, when applicable and clinically feasible, non-injected lesions.
• Male or female patients from the age of 18 years.
• ECOG Performance Status/WHO Performance Status ≤ 1.

You may not qualify if:

• Previous or concurrent cancer type that is distinct from the cancers being evaluated in this study, exception made for any other cancer curatively treated ≥ 2 years prior to study entry. Patients suffering from cSCC post-organ transplantation, or cSCC patients with concomitant chronic lymphocytic leukemia are excluded from the study.
• Previous topical or systemic chemotherapy, immunotherapy, or radiation therapy at the tumor sites within 4 weeks prior to study drug administration.
• 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, HCV and Covid-19 excluding active infection is needed.
• Impaired cardiocirculatory functions due to any of the following conditions:
• 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).
• Any 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).
• Known arterial aneurysms.
• INR \> 3.
• Known uncontrolled coagulopathy or bleeding disorder.
• Known hepatic cirrhosis or severe pre-existing hepatic impairment.
• Moderate to severe respiratory failure.

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (14)

Hôpital de la Timone

Marseille, 13 005, France

RECRUITING

CHU de Nantes - Hôpital Dieu

Nantes, 44093, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94800, France

RECRUITING

IRCCS Istituto Clinico Humanitas

Rozzano, Milano, Italy

NOT YET RECRUITING

Istituto Nazionale dei Tumori Fondazione IRCCS

Milan, 20133, Italy

RECRUITING

IRCCS Istituto Nazionale Tumori "Fondazione Giovanni Pascale"

Napoli, 80131, Italy

RECRUITING

Istituto Oncologico Veneto IOV

Padua, 35128, Italy

NOT YET RECRUITING

IFO- Istituto Dermatologico San Gallicano

Roma, 00144, Italy

NOT YET RECRUITING

Fondazione Policlinico Universitario A. Gemelli Università Cattolica del Sacro Cuore

Roma, 00168, Italy

RECRUITING

Azienda Ospedaliero Universitaria Senese Policlinico Le Scotte

Siena, 53100, Italy

NOT YET RECRUITING

Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI)

Trieste, 34125, Italy

RECRUITING

Hospital Clinic Barcelona

Barcelona, 08036, Spain

NOT YET RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

NOT YET RECRUITING

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

RECRUITING

MeSH Terms

Conditions

Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carcinoma, Merkel Cell; Sarcoma, Kaposi

Interventions

daromun

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell; Neoplasms, Squamous Cell; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Adenocarcinoma; Neoplasms, Nerve Tissue; Herpesviridae Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Vascular Tissue

Central Study Contacts

Lisa Nadal, PhD

CONTACT

+39 0577 17816; regulatory@philogen.com

Marco Taras

CONTACT

regulatory@philogen.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase II, open label, multicentric, proof-of-principle basket trial in patients with malignant tumors of the skin amenable to intratumoral injection, and in a curative or neoadjuvant or palliative intention.

Study Record Dates

• First Submitted: April 7, 2022
• First Posted: April 15, 2022
• Study Start: March 9, 2023
• Primary Completion: June 1, 2024
• Study Completion: December 1, 2024
• Last Updated: October 6, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); IT (8); FR (3)