E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 according to the evaluation of a local interdisciplinary tumor board or who refuse surgery and for whom an histological evaluation is available according to international guidelines |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Objective Response Rate - ORR (Complete Response (CR) + Partial Response (PR)) for each tumor type measured at Day 36 (Week 6, Tumor Assessment/Safety visit) from beginning of treatment according to RECIST v1.1 criteria. |
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E.2.2 | Secondary objectives of the trial |
Pathological response for each tumor at the time of surgery and safety of intratumoral administration of L19Il2/L19TNF |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with high-risk, locally advanced (non-metastatic, node negative, single or multifocal), BCC or cSCC amenable to intratumoral injection, not eligible to surgery according to the evaluation of a local interdisciplinary tumor board or who refuse surgery and for whom an histological evaluation is available according to international guidelines. • 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 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.
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective Response Rate - ORR (Complete Response (CR) + Partial Response (PR)) for each tumor type measured at Day 36 (Week 6, Tumor Assessment/Safety visit) from beginning of treatment according to RECIST v1.1 criteria. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Objective Response Rate - ORR (Complete Response (CR) + Partial Response (PR)) for each tumor type are measured at Day 36 (Week 6, Tumor Assessment/Safety visit) from beginning of treatment according to RECIST v1.1 criteria. |
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E.5.2 | Secondary end point(s) |
- Pathological Response for each tumor type - Safety of intratumoral administration of L19IL2/L19TNF |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Pathological Response for each tumor type at the time of surgery. - Safety of intratumoral administration of L19IL2/L19TNF at every administration and throughout the study.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |