Safety and Early Signs of Efficacy of IL12-L19L19.
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-80
SponsorPhilogen S.p.A.
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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).
Trial design
Design model
Sequential
Treatments tested in this trial
IL12-L19L19
DrugPart 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.
IL12-L19L19
DrugPatients initially receive 8 consecutive administrations of IL12-L19L19 every week. At the end of this eight weeks treatment window, a tumor assessment is performed and those patients who achieve a clinical benefit (SD, PR, CR) may continue treatment with IL12-L19L19 as a biweekly maintenance therapy until disease progression, unacceptable toxicity, withdrawal of consent, at the discretion of the investigator or up to 1 year from study treatment start.
Treatment groups
80 Participants
are divided into 1 treatment groupGroup A: TreatmentExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
For Part I: DLT
Occurrence of dose limiting toxicity (DLT) in dose escalation part of the study.
Time frame
From Day 1 to Day 28 of the treatment2
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)
Time frame
From Day 1 to Day 28 of the treatment3
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.
Time frame
From Day 1 to Day 28 of the treatment4
Safety (AE)
Safety of administration of IL12-L19L19, through an assessed by Common Toxicity Criteria (version 5.0, CTCAE)
Time frame
Throughout study completion for each patientSecondary outcomes
1
Plasma concentration of IL12-L19L19
Evaluation of individual plasma concentration of IL12-L19L19
Time frame
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 infusion2
AUC of IL12-L19L19
Estimation of AUC of IL12-L19L19, as data permit
Time frame
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 infusion3
Tmax of IL12-L19L19
Estimation of Tmax of IL12-L19L19, as data permit
Time frame
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 infusion4
T1/2 of IL12-L19L19
Estimation of T1/2 of IL12-L19L19, as data permit
Time frame
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 infusionSponsors and contacts
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Source ClinicalTrials.gov