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JOURNAL ONKOLOGIE – STUDIE
DUNCAN

Intratumoral Administration of Daromun in Non-melanoma Skin Cancer Patients

Rekrutierend

NCT-Nummer:
NCT04362722

Studienbeginn:
September 2020

Letztes Update:
10.10.2023

Wirkstoff:
L19IL2 +L19TNF

Indikation (Clinical Trials):
Carcinoma, Skin Neoplasms, Carcinoma, Basal Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Philogen S.p.A.

Collaborator:
-

Kontakt

Studienlocations
(3 von 11)

Alle anzeigen

Studien-Informationen

Brief Summary:

This clinical phase II study is designed to investigate the efficacy of intratumorally

administered L19IL2/L19TNF in patients with injectable lesions of BCC or cSCC. Favorable

tumor responses following intralesional treatment with L19IL2/L19TNF have been observed in

patients with injectable melanoma lesions of stage III or IV, for injected and non-injected

lesions.

The proposed clinical phase II study plans to investigate the intralesional administration of

6.5 Mio IU of L19IL2 (~1.08 mg) and 200 µg of L19TNF to be administered in an approximate

volume of 1.0 mL as a single or multiple intratumoral injections in patients with high-risk

BCC or cSCC.

There is a high medical need for non-invasive therapeutic strategies with a comparable good

response rate and high recurrence free survival for treatment of patients with BCC or cSCC,

who cannot be treated by or refuse surgery. Surgery is not always applicable, as it may not

be feasible due to the anatomic location, may have a poor cosmetic outcome for the patient or

is generally not accepted as treatment strategy by the patient. However, current non-surgical

treatment strategies have a considerably reduced response rate and recurrence free survival.

Based on the favorable results for injected and non-injected lesions obtained in the phase II

study of L19IL2/L19TNF and the good safety profile seen in the subsequent phase III study,

both in stage III or IV melanoma patients, we believe, that patients with BCC or cSCC will

profit from intralesional treatment with L19IL2/L19TNF.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- High-risk, localized (non-metastatic, node negative, single or multifocal) BCC or cSCC

amenable to intratumoral injection.

- Patients with injectable and measurable regional cutaneous or subcutaneous in-transit

or satellite metastasis but without regional nodal involvement are also eligible.

- Male or female patients, age 18 - 100 years.

- ECOG Performance Status/WHO Performance Status ≤ 1.

- Hemoglobin > 10.0 g/dL.

- Platelets > 100 x 10^9/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.

Exclusion Criteria:

- 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.

- Patients may have previously received topical or systemic chemotherapy, immunotherapy

or radiation therapy on the tumor sites. Such therapies must be completed at least 4

weeks prior to study drug administration.

- Patients with node positive BCC/cSCC who are candidate to SHH inhibitor or checkpoint

inhibitor therapy.

- 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.

- History within the last year of acute or subacute coronary syndromes including

myocardial infarction, unstable or severe stable angina pectoris, inadequately treated

cardiac arrhythmias and heart insufficiency (any grade, New York Heart Association

(NYHA) criteria).

- Any abnormalities observed during baseline ECG investigations that are considered

clinically significant by the investigator.

- Known arterial aneurysms.

- INR > 3.

- Uncontrolled hypertension.

- 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 (>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.

- Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies.

- Pregnancy or breast-feeding.

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

- Severe diabetic retinopathy.

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

- Solid organ transplant recipient or patient with iatrogenic or pathologic severe

immune suppression.

- Any conditions that in the opinion of the investigator could hamper compliance with

the study protocol.

Studien-Rationale

Primary outcome:

1. Efficacy of L19IL2/L19TNF in CR (Time Frame - Tumor Assessment/Safety visit (Week 6, Day 36)):
Objective Response Rate (Complete Response CR) for each tumor type from beginning of treatment according to RECIST v1.1 criteria.

2. Efficacy of L19IL2/L19TNF in PR (Time Frame - Tumor Assessment/Safety visit (Week 6, Day 36)):
Objective Response Rate (Partial Response PR) for each tumor type from beginning of treatment according to RECIST v1.1 criteria.

Secondary outcome:

1. Pathological Response (Time Frame - At Surgery):
Efficacy of L19IL2/L19TNF measured as Pathological Response for each tumor type at the time of surgery.

2. Safety (AE) (Time Frame - Throughout study completion for each patient, an average of 12 weeks for each patient):
Safety of intratumoral administration of L19IL2/L19TNF, assessed by Common Toxicity Criteria (version 5.0, CTCAE)

3. Safety: ECG (Time Frame - Before first drug administration at Day 1 and at the Tumor Assessment Visit at Day 36 (Week 6).):
Electrocardiogram (ECG) findings. In particular, data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment

4. Safety: change in vital signs (Time Frame - Before first drug administration at Day 1, Day 8, Day 15, Day 22 and at the Tumor Assessment Visit at Day 36 (Week 6).):
Measurement of heart rate (beats per minute)

5. Safety: change in vital signs (Time Frame - Before first drug administration at Day 1, Day 8, Day 15, Day 22 and at the Tumor Assessment Visit at Day 36 (Week 6).):
Measurement of blood pressure (mmHg)

Geprüfte Regime

  • L19IL2 +L19TNF (bifikafusp alfa + onfekafusp alfa):
    Single or multiple intratumoral administration of a mixture of L19IL2 and L19TNF will be performed once weekly for up to 4 weeks into all injectable lesions present at the beginning of treatment or appearing during treatment phase The dose will be constituted by 6.5 Mio IU L19IL2 (~1.08 mg) and 200 µg L19TNF.

Quelle: ClinicalTrials.gov


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