AzTrials
AzTrials

BCC - Basal Cell CarcinomaPhase 2IntriNSiCNCT05329792

L19IL2/L19TNF in Skin Cancer Patients

A Phase 2 study testing L19IL2/L19TNF in people with BCC - Basal Cell Carcinoma and SCC - Squamous Cell Carcinoma, run by Philogen S.p.A. at 14 sites in 3 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 100 years
What is being tested?
L19IL2/L19TNF
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
14 sitesin 3 countries
Study dates
9 Mar 2023to Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 25Show fewer
  • 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.
  • CTCL: Tumoral stage of Mycosis fungoides subtypes which are resistant to usual systemic treatments. In order to validate the first inclusion criterion of this trial, the tumor board will take into account that the treatment under investigation is intended to be only a palliative local therapy and cannot compete with a general efficacious strategy, if any.
  • KS: Classic or endemic, histologically confirmed KS, particularly when local response can be considered of either functional or cosmetic benefit. In order to validate the first inclusion criterion of this trial, the tumor board will take into account that the treatment under investigation is intended to be only a palliative local therapy and cannot compete with a general efficacious strategy, if any.
  • 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.
  • Hemoglobin > 10.0 g/dL.
  • Platelets > 100 x 109/L.
  • ALT and AST, GGT and Lipase ≤ 1.5 x the upper limit of normal (ULN).
  • Serum creatinine < 1.5 x ULN and GFR > 60 mL/min.
  • 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.
  • 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.
  • 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.
  • Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

Who cannot join

  • 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.
Show all 23Show fewer
  • 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.
  • Active autoimmune disease.
  • Patient requires or is taking systemic corticosteroids 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.
  • Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies.
  • Pregnancy or breast-feeding.
  • Severe diabetic retinopathy.
  • Recovery from major trauma including surgery within 4 weeks prior to enrollment.
  • Patient with iatrogenic or pathologic severe immune suppression.
  • Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.

Trial locations and contacts

14 sites in 3 countries.

Lisa Nadal, PhD contact

+39 0577 17816

regulatory@philogen.com

Marco Taras contact

regulatory@philogen.com

14 sites in 3 countries

Italy8 sites, 8 recruiting

  • Istituto Nazionale dei Tumori Fondazione IRCCS

    Milan, 20133

    Umberto Cortinovis

    Recruiting

  • IRCCS Istituto Nazionale Tumori "Fondazione Giovanni Pascale"

    Naples, 80131

    Paolo Antonio Ascierto

    Recruiting

  • Istituto Oncologico Veneto IOV

    Padova, 35128

    Francesco Russano, Dr.

    Not yet recruiting

  • IFO- Istituto Dermatologico San Gallicano

    Roma, 00144

    Pasquale Frascione, Dr.

    Not yet recruiting

  • Fondazione Policlinico Universitario A. Gemelli Università Cattolica del Sacro Cuore

    Roma, 00168

    Ketty Peris

    Recruiting

  • IRCCS Istituto Clinico Humanitas

    Rozzano, Milano

    Paolo Bossi

    Not yet recruiting

  • Azienda Ospedaliero Universitaria Senese Policlinico Le Scotte

    Siena, 53100

    Anna Maria Di Giacomo

    Not yet recruiting

  • Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI)

    Trieste, 34125

    Iris Zalaudek

    Recruiting

Other trials in Italy

France3 sites, 3 recruiting

  • Hôpital de la Timone

    Marseille, 13 005

    Jean-Jacques Grob, MD

    Recruiting

  • CHU de Nantes - Hôpital Dieu

    Nantes, 44093

    Gaëlle Quereux

    Recruiting

  • Institut Gustave Roussy

    Villejuif, 94800

    Caroline Robert

    Recruiting

Other trials in France

Spain3 sites, 3 recruiting

  • Hospital Clinic Barcelona

    Barcelona, 08036

    Agustí Toll Abelló, Dr.

    Not yet recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

    Pablo Luis Ortiz Romero, Dr.

    Not yet recruiting

  • Hospital Universitario Virgen Macarena

    Seville, 41009

    David Moreno Ramirez, MD

    Recruiting

Other trials in Spain

About this study

Official title: A Phase II Study of L19IL2/L19TNF in Patients With Skin Cancers Amenable to Intralesional Treatment

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.

Read the detailed description

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.

In the study, 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.

Tumor assessment:

  • Tumor assessment (TA) visits will be performed at Week 12 (Day 78 from the beginning of treatment), then every 8 weeks and up to Week 52 after beginning of treatment. For confirmation of objective responses, unscheduled visits will be performed 4 weeks after the visit, which the objective response was first recorded at.
  • During each TA visit, measurement of tumor lesions and documentation (photographic documentation with use of a caliper for cutaneous lesions; ultrasound for subcutaneous lesions; imaging techniques as deemed appropriate/necessary by treating physician) will be performed. The choice of the most suitable instrumental technique to measure and document evolution of the disease will be made by the treating physician at baseline screening, the same technique will have to be used for all following tumor assessments.
  • Histological assessment of tumor tissue: estimation of percent of residual viable tumor cells and tumor infiltration with immune responsive cell. Locally performed histological specimen assessment will be centrally reviewed.

After confirmed partial responses, surgery with curative intent is allowed (if considered feasible and of potential benefit for the patients by the treating physician) and will be performed no later than 4 weeks after the TA visit at which the partial response is confirmed.

Safety assessment:

  • The safety profile of intratumoral administration of L19IL2/L19TNF will be assessed throughout the study. A complete safety assessment will be performed at the safety visit.

Human-anti-fusion protein antibodies (HAFA) assessment:

  • The possible development of antibodies against L19IL2 or L19TNF will be verified. Samples will be collected before L19IL2/L19TNF administration at Days 1, 22 and Day 78 (TA visit).

A Data and Safety Monitoring Board (DSMB), composed of expert dermato-oncologists, will evaluate safety and efficacy data after the first 20 patients and will formulate recommendations for the prosecution of the study.

Being tested
L19IL2/L19TNF
Medical subject headings
Carcinoma, Basal Cell, Carcinoma, Squamous Cell, Carcinoma, Merkel Cell, Sarcoma, Kaposi

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • L19IL2/L19TNFDrug

    Also called bifikafusp alfa/onfekafusp alfa

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

Study groups in NCT05329792
Study groupRoleWhat they receive
Treatment arm with L19IL2 /L19TNFExperimental70 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.
Receives: Drug: L19IL2/L19TNF

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Visit will be performed at week 12

Secondary outcomes (6)

  1. Disease control rate (DCR)

    Disease control rate (DCR) [Complete Response (CR) + Partial Response (PR) + Stable Disease (SD)] for each tumor type measured according to RECIST v1.1 criteria.

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

  2. Local PFS (LPFS)

    Local Progression Free Survival (LPFS) on the treated tumors only

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

  3. Progression-free survival (PFS)

    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,

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

  4. Adverse Events (AE)

    Percentage of Patients in Each Treatment Group with AEs, AEs with CTCAE grade ≥3

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

  5. Serious Adverse Event (SAEs)

    Percentage of Patients in Each Treatment Group with Drug-Related Adverse Events, Serious Adverse Event (SAEs)

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

  6. Human anti-fusion protein antibodies (HAFA)

    Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19IL2 and L19TNF

    Measured: At week 1, at week 4 and at week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2022
  2. Study start9 Mar 2023
  3. Primary completionJun 2024 (estimated)
  4. Study completionDec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05329792
Sponsor's protocol ID
PH-L19IL2TNFBASK-04/21
Acronym
IntriNSiC
Status last verified
Oct 2023
First submitted
7 Apr 2022
Last updated
6 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Patel JD, Pozorski VJ, Tavberidze N, Buehler DG, Huang W, Bennett DD, Ma VT. Successful Treatment of Metastatic Primary Cutaneous Adnexal Carcinoma With a PD-1 Inhibitor. J Immunother. 2024 Oct 1;47(8):323-327. doi: 10.1097/CJI.0000000000000522. Epub 2024 Apr 26.

    PubMed 38664936

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing L19IL2/L19TNF in people with BCC - Basal Cell Carcinoma and SCC - Squamous Cell Carcinoma, run by Philogen S.p.A. at 14 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 6 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Italy, France, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Lisa Nadal, PhD (+39 0577 17816, regulatory@philogen.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Confirmed best overall response rate (BORR) (time frame: Visit will be performed at week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05329792, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in