Safety and Early Signs of Efficacy of IL12-L19L19.

NCT04471987 | Recruiting Phase 1 DMC

• 2 other identifiers: PH- IL12L19L19-01/192024-510841-32-00
• Study Type: interventional
• Target: 80
• Locations: 3 countries
• Sites: 11

Brief Summary

The purpose of this study is to describe the safety, tolerability and early signs of efficacy of the antibody-cytokine fusion protein IL12-L19L19 in patients with advanced or metastatic solid carcinomas, after previous immune checkpoint blockade therapy. The primary objective of the study is to evaluate the safety of IL12-L19L19 and to establish MTD in order to establish a recommended dose (RD). The secondary objectives of the study are to assess early signs of efficacy, the determination of pharmacokinetic (PK) properties and the immunogenicity of IL12-L19L19.

Conditions

Metastatic Solid Tumor; Advanced Solid Tumor

Outcome Measures

Primary Outcomes (6)

• For Part I: DLT

  Occurrence of dose limiting toxicity (DLT) in dose escalation part of the study.

  From Day 1 to Day 28 of the treatment

• For Part I: MAD

  Definition of Maximum Administered Dose (MAD) (in dose escalation part). The MAD is defined when at least two patients within a cohort of 2-6 patients experience a DLT (i.e., ≥33% of patients with a DLT at that dose level)

  From Day 1 to Day 28 of the treatment

• For Part I: MTD and RD

  Defining the Maximum Tolerated Dose (MTD) and recommendation of the Recommended Dose (RD): when the DLT rate reaches 33% in a cohort, the next lower dose level will be called the MTD (so long as the DLT rate is less than 33%). Accordingly, the recommended dose (RD) for the Dose Expansion cohort will be the MTD.

  From Day 1 to Day 28 of the treatment

• Safety (AE)

  Safety of administration of IL12-L19L19, through an assessed by Common Toxicity Criteria (version 5.0, CTCAE)

  Throughout study completion for each patient

• Safety (SAE)

  Safety of administration of IL12-L19L19, assessed by Common Toxicity Criteria (version 5.0, CTCAE)

  Throughout study completion for each patient

• Safety (DILI)

  Evaluation of possible Drug Induce Liver Injury, caused by IL12-L19L19, assessed by Common Toxicity Criteria (version 5.0, CTCAE)

  Throughout study completion for each patient, a maximum of 24 weeks for each patient

Secondary Outcomes (10)

• Plasma concentration of IL12-L19L19

  30 min prior injection in week from 1 to 8, at End-of-Treatment Visit and Follow Up 1; in week 1 and 3: 15 min after start of infusion, 60 min after start of infusion, end of infusion, 2h, 4h and 24h after end of infusion

• AUC of IL12-L19L19

  In week 1 and 3: 15 min after start of infusion, 60 min after start of infusion, end of infusion, 2 h after end of infusion, 4 h after end of infusion, 24 h after end of infusion

• Tmax of IL12-L19L19

  In week 1 and 3: 15 min after start of infusion, 60 min after start of infusion, end of infusion, 2 h after end of infusion, 4 h after end of infusion, 24 h after end of infusion

• T1/2 of IL12-L19L19

  in week 1 and 3: 15 min after start of infusion, 60 min after start of infusion, end of infusion, 2 h after end of infusion, 4 h after end of infusion, 24 h after end of infusion

• Cmax of IL12-L19L19

  in week 1 and 3: 15 min after start of infusion, 60 min after start of infusion, end of infusion, 2 h after end of infusion, 4 h after end of infusion, 24 h after end of infusion

Study Arms (1)

Treatment

EXPERIMENTAL

The study will take place in two stages: 1. In the dose escalation part, participants will be enrolled in cohorts and will be treated with different doses of IL12-L19L19 in order to identify a RD to be further explored in the subsequent dose expansion part. In the dose escalation part, patients will be treated in cohorts of 1 to 6 patients with escalating doses of IL12-L19L19 until the MAD is reached. 2. Following successful identification of the RD, the study will proceed with a dose expansion part and 20 patients will be treated at the RD dose level.

Drug: IL12-L19L19

Interventions

IL12-L19L19 DRUG

Part I - The dose escalation is designed with an initial accelerated phase followed by a standard 3+3 design. Cohorts contain one patient until first instance of moderate toxicity or a DLT in the DLT observation period (28 days). With the second occurrence of moderate toxicity or occurrence of a DLT the accelerated phase will be terminated and the dose escalation will continue with a 3+3 dose escalation. Initiation of the study treatment for an individual subject will occur not less than 7 days after initiation of the study treatment for the previous patient. Not more than 2 patients are to be treated simultaneously within their DLT observation period (i.e., Day 1 to Day 28). Part II - Dose expansion: Once the dose escalation is completed, additional 20 patients will be enrolled at the RD to better understand the safety profile and to explore early signs of efficacy in different disease indications.

Also known as: Dodekin

Treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female aged 18 to 80 years at the time of consent.
• Patients must have a histological or cytological diagnosis of advanced/metastatic immunotherapy responsive solid carcinoma for which immune checkpoint blockade is approved, that has progressed on immune checkpoint-blockade therapy.
• Patients must have received an immune checkpoint blockade therapy-based regimen as prior treatment.
• Only patients without other therapeutic alternatives with curative or survival prolonging potential per investigator judgement are able to participate.
• Subjects must have had clinical benefit in terms of disease control (CR/PR/SD) while on checkpoint inhibitor treatment defined as ≥ 3 month free from progression from initial imaging documenting advanced/metastatic disease followed by radiographic disease progression after checkpoint inhibitor per investigator's opinion.
• Patients must have progressive disease or relapse at the time of screening.
• Patients may have previously received chemotherapy, immunotherapy or radiation therapy. Such therapies must be completed at least 4 weeks prior to study drug administration. Radiotherapy within 4 weeks of the first dose of study drug, is allowed for palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass. During the expansion part, to allow evaluation of response to treatment, patients must have remaining measurable disease that has not been irradiated.
• Eastern cooperative oncology group (ECOG) performance status ≤ 2.
• Patient has an estimated life expectancy of at least 12 weeks.
• At least one unidimensionally measurable lesion either by computed tomography (CT), MRI or PET/CT as defined by RECIST (v. 1.1) for solid tumors.
• Documented negative test for HIV-HBV-HCV. For HBV serology: the determination of HBsAg, and anti-HBcAg-Ab is required. In patients with serology documenting previous exposure to HBV (i.e., anti-HBs Ab with no history of vaccination and/or anti-HBc Ab), negative serum HBV-DNA is required. For HCV: HCV-RNA or HCV antibody test. Subjects with a positive test for HCV antibody but no detection of HCV-RNA indicating no current infection are eligible.
• All acute toxic effects (excluding alopecia and fatigue) of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v. 5.0) Grade ≤ 1.
• Full resolution of checkpoint blockade therapy-related adverse effects (including immune-related adverse effects) and no treatment for these AEs for at least 4 weeks prior to the time of enrollment. The only exception are patients with checkpoint blockade induced hypothyroidism and hypophysitis if these patients are on stable maintenance therapy with on levothyroxine or steroids (≤ 10 mg prednisone equivalent) for at least 2 months prior dosing.
• No history of severe immune related adverse effects from prior given immune checkpoint blockade therapy (CTCAE Grade 4; CTCAE Grade 3 requiring treatment \>4 weeks).
• Female patients: negative blood pregnancy test at Screening for women of childbearing potential (WOCBP)\*. WOCBP must agree to use, from the screening to six 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 (www.hma.eu/ctfg.html) 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 or vasectomized partner.

You may not qualify if:

• Subjects who participated in an investigational drug or device study within 4 weeks prior to study treatment start.
• Radiotherapy within 4 weeks prior to study treatment start.
• Active or history of autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent.
• Patients with primary brain tumors or CNS disease (including brain metastases).
• Patient taking herbal medications within 7 days prior to study treatment start.
• Known history of allergy to an excipient in study medication or any other intravenously administered human proteins/peptides/antibodies.
• Absolute neutrophil count (ANC) \< 1.5 x 10\^9/L, platelets \< 100 x 10\^9/L or haemoglobin (Hb) \< 9.0 g/dl.
• Chronically impaired renal function as indicated by creatinine clearance \< 60 mL/min or serum creatinine \> 1.5 ULN.
• Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol, in the opinion of the investigator.
• History within the last year of cerebrovascular disease and/or acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
• Heart insufficiency (\> Grade II, New York Heart Association (NYHA) criteria).
• Clinically significant cardiac arrhythmias or requiring permanent medication.
• Abnormal LVEF or any other abnormalities observed during baseline ECG and echocardiogram investigations that are considered as clinically significant by the investigator. Subjects with current, or a history of QT/QTc prolongation would be excluded. In particular:
• patients with a marked prolongation of QT/QTc interval (e.g., repeated demonstration of QTc \>480 milliseconds using Fredricia's QT correction formula) are excluded;
• patients with a history of risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of prolonged QT syndrome) are excluded;

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (11)

Universitaetsklinik Hamburg-Eppendorf

Hamburg, Hamburg, Germany

RECRUITING

Universitätsklinikum Heidelberg, Nationalen Centrum für Tumorerkrankungen (NCT), Dermatoonkologie

Heidelberg, Heidelberg, 69120, Germany

RECRUITING

Universitätsklinikum Leipzig, Klinik für Dermatologie, Venerologie und Allergologie

Leipzig, Leipzig, 04103, Germany

RECRUITING

Universitätsklinikum Tübingen, Klinik für Innere Medizin VIII Medizinische Onkologie und Pneumologie

Tübingen, 72076, Germany

RECRUITING

IEO - Istituto Europeo di Oncologia

Milan, Italy, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Azienda Ospedaliero-Universitaria San Luigi Gonzaga

Orbassano, Italy

NOT YET RECRUITING

Universitätsspital Basel

Basel, Basel, CH-4031, Switzerland

RECRUITING

Insel Gruppe AG

Bern, Canton of Bern, 3010, Switzerland

RECRUITING

Geneva University Hospital, Oncology Department

Geneva, Canton of Geneva, 1211, Switzerland

RECRUITING

Oncology Institute of Southern Switzerland

Bellinzona, 6500, Switzerland

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jacqueline Mock, PhD

CONTACT

+41 435448804; regulatory@philogen.com

Federica Bastioli, Pharmaceutical Chemist

CONTACT

+39 057717816; regulatory@philogen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective, open-label, non-randomized, multiple ascending dose, phase I dose escalation trial in patients with advanced solid carcinomas after previous immune-checkpoint blockade therapy conducted in sequential cohorts of patients followed by a dose expansion part.

Study Record Dates

• First Submitted: July 7, 2020
• First Posted: July 15, 2020
• Study Start: July 1, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4); CH (4); IT (3)