The study will assess the safety, tolerability, PK and efficacy of different intra-tumoral dosing regimens of LTX-315; a lytic-peptide that induces long-term anti-cancer immune responses, as monotherapy or in combination with ipilimumab or pembrolizumab.
In this phase I, open-label, multi-arm, multicentre, multi-dose dose escalation study in patients with transdermally accessible tumours; the safety, PK and efficacy of different dosing regimens of LTX-315 will be assessed. Patients will be allocated into 4 separate (parallel) arms depending on the tumour type and the number of lesions available. Arm A: Single lesion/sequential lesion treatment arm (LTX-315 monotherapy) (Completed) Arm B: Concurrent multiple lesion treatment arm with all tumour types (LTX-315 monotherapy) Arm C: LTX-315 combination with ipilimumab in patients with melanoma Arm D: LTX-315 combination with pembrolizumab in patients with TNBC All patients will have at least one lesion available for injection. Treatment schedule: Arm A: Injection of LTX-315 3 days week 1, 1 day in week 2, 3, 4, 5 and 6. Every 2 weeks starting with week 8. Arm B (all tumours): Injection of LTX-315 2 days week 3 weeks (Day 1, 2, 8, 9, 15 and 16). Arm C (melanoma): Injection of lTX-315 2 days week 3 weeks (Day 1, 2, 8, 9, 15 and 16) in combination with ipilimumab given in week 1 and every 3 weeks 4 cycles. Arm D (TNBC): Injection of LTX-315 2 days week 3 weeks (Day 1, 2, 8, 9, 15 and 16) in combination with pembrolizumab given in week 1 and every 3 weeks up to 2 years. Patients will be enrolled into a dose cohort in order of study entry. Staring with the lowest dose. A minimum of 3 patients will be enrolled into each cohort. Dose escalation determined by the Safety Review Committee and the Sponsor. The the optimal regimen will be based on the results of the Dose Escalation from the following information: 1. Safety parameters including blood samples and cardiovascular effects 2. Immunohistology and ultrasound confirmation of necrosis and tumour infiltrating lymphocytes 3. Systemic inflammatory response 4. Evidence of clinical responses Cohorts may be utilized to: 1. Evaluate different doses of LTX-315 2. Explore potential modifications to the dosing schedule 3. Evaluate the potential to include appropriate combination therapies with LTX-315 4. Gain further information on clinical efficacy
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Dose escalation: Cohort 1: 2 mg twice per day (4 mg) Cohort 2: 3 mg twice per day (6 mg) Cohort 3: 4 mg twice per day (8 mg)
Dose escalation: Cohort 1: 3 mg per injection Cohort 2: 4 mg per injection Cohort 3: 5 mg per injection
Cohort 1: 3 mg per injection + 3 mg/kg ipilumumab Cohort 2: 4 mg per injection + 3 mg/kg ipilumumab Cohort 3: 5 mg per injection + 3 mg/kg ipilumumab
Jules Bordet Institute
Brussels, Belgium
Cliniques Universitaires St-Luc, Service d'oncologie médicale
Brussels, Belgium
Institut Curie
Paris, France
Dose limiting toxicity
Dose limiting toxicities (DLT) and the overall safety profile (adverse events (AE), laboratory assessments, physical findings and symptomatic assessment) of LTX-315 as monotherapy and in combination with ipilimumab or pembrolizumab.
Time frame: 21 days
Anti tumour activity in injected tumour
Number of patients with regression of injected tumour assessed by ultrasound and/or CT/MRI.
Time frame: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed
Complete response (irCR) and partial response (irPR)
Number of patients by irRC
Time frame: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed
Overall response rate (OR)
(irRC criteria)
Time frame: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed
Disease control rate (CR + PR + SD)
irRC criteria
Time frame: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed
Progression free survival (PFS)
irRC criteria
Time frame: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Cohort 1: 3 mg per injection + 200 mg pembrolizumab Cohort 2: 4 mg per injection + 200 mg pembrolizumab Cohort 3: 5 mg per injection + 200 mg pembrolizumab
Institute Gustave Roussy
Paris, France
Intotuto Europeo di Oncologia (IEO)
Milan, Italy
San Raffaele Hospital
Milan, Italy
Intituto Nazionale dei Tumori
Naples, Italy
Instituto Oncologico Venneto (IOV)
Padova, Italy
Haukeland University Hospital
Bergen, Norway
Oslo University Hospital Radiumhospitalet
Oslo, Norway
...and 4 more locations