Clinical Trials /

Intratumoral Administration of Daromun in Non-melanoma Skin Cancer Patients

NCT04362722

Description:

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.

Related Conditions:
  • Basal Cell Carcinoma
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Intratumoral Administration of Daromun in Non-melanoma Skin Cancer Patients
  • Official Title: A Phase II Study of Intratumoral Administration of L19IL2/L19TNF in Non-melanoma Skin Cancer Patients With Presence of Injectable Lesions

Clinical Trial IDs

  • ORG STUDY ID: PH-L19IL2TNFNMSC-04/19
  • NCT ID: NCT04362722

Conditions

  • Carcinoma, Basal Cell
  • Carcinoma, Cutaneous Squamous Cell

Interventions

DrugSynonymsArms
L19IL2 +L19TNFbifikafusp alfa + onfekafusp alfaSingle arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Single armExperimental40 patients will be enrolled and treated with a mixture of 6.5 Mio IU (~1.08 mg) L19IL2 and 200 µg L19TNF once weekly for 4 consecutive weeks. The dose will be distributed among the lesions via multiple intralesional injections. New lesions occurring during the treatment phase will also be treated as described but the treatment period for new lesions will not be extended beyond the previously defined 4 weeks treatment period with clock-start at the time of the first intralesional L19IL2/L19TNF injection. After the Tumor Assessment/Safety visit, patients may receive surgery in a curative intention within 6 weeks, in order to assess the pathological response with estimation of percent of residual viable tumor cells.
  • L19IL2 +L19TNF

Eligibility Criteria

        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.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Pathological Response
Time Frame:At Surgery
Safety Issue:
Description:Efficacy of L19IL2/L19TNF measured as Pathological Response for each tumor type at the time of surgery.
Measure:Safety (AE)
Time Frame:Throughout study completion for each patient, an average of 12 weeks for each patient
Safety Issue:
Description:Safety of intratumoral administration of L19IL2/L19TNF, assessed by Common Toxicity Criteria (version 5.0, CTCAE)
Measure:Safety: ECG
Time Frame:Before first drug administration at Day 1 and at the Tumor Assessment Visit at Day 36 (Week 6).
Safety Issue:
Description:Electrocardiogram (ECG) findings. In particular, data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment
Measure: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).
Safety Issue:
Description:Measurement of heart rate (beats per minute)
Measure: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).
Safety Issue:
Description:Measurement of blood pressure (mmHg)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Philogen S.p.A.

Last Updated

April 22, 2020