LTX-315 in Patients With Transdermally Accessible Tumours as Monotherapy or Combination With Ipilimumab or Pembrolizumab
|Cancer Melanoma Breast Cancer Head and Neck Cancer Lymphoma Triple-Negative Breast Cancer||Drug: LTX-315 consecutive lesions Drug: LTX-315 Drug: LTX-315 + ipilimumab Drug: LTX-315 + pembrolizumab||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase I, Open-label, Multi-arm, Multi-centre, Multi-dose, Dose Escalation Study of LTX-315 as Monotherapy or in Combination With Either Ipilimumab or Pembrolizumab in Patients With Transdermally Accessible Tumours|
- Dose limiting toxicity [ Time Frame: 21 days ]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.
- Anti tumour activity in injected tumour [ Time Frame: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed ]Number of patients with regression of injected tumour assessed by ultrasound and/or CT/MRI.
- Complete response (irCR) and partial response (irPR) [ Time Frame: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed ]Number of patients by irRC
- Overall response rate (OR) [ Time Frame: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed ](irRC criteria)
- Disease control rate (CR + PR + SD) [ Time Frame: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed ]irRC criteria
- Progression free survival (PFS) [ Time Frame: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed ]irRC criteria
- Pharmacokinetic (PK) profile of LTX-315 [ Time Frame: Pre and 1 hour post dosing Day 2 Week 1 ]Measurement of plasma concentrations of LTX-315 pre- and 1 hour post-dosing day 2 in week 1.
|Actual Study Start Date:||November 2013|
|Estimated Study Completion Date:||October 2017|
|Estimated Primary Completion Date:||October 2017 (Final data collection date for primary outcome measure)|
Experimental: Arm A: LTX-315 monotherapy singe lesion
Cohort 1-3: First induction treatment (6 weeks): In week 1 the first index lesion will be injected Twice daily on 3 consecutive days. During week 2-6 the injection will be once a week.
Second induction treatment (6 weeks) and Maintenance treatment (20 weeks)- At week 7 the second index lesion will be injected with same dosing schedule as the first index lesion.
Cohort 4 and above: Once daily on 3 consecutive days week 1. Week 2-6 one injection per week. From week 8, one dosing days every 2 weeks.
Drug: LTX-315 consecutive lesions
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)
Other Name: Protocol version 4
Experimental: Arm B: LTX-315 monotherapy in multiple concurrent lesions
Patients with at least one injectable lesion and one bystander lesion will receive LTX-315 to one or more lesions:
Once daily on 2 consecutive days week 1-3.
Cohort 1: 3 mg per injection Cohort 2: 4 mg per injection Cohort 3: 5 mg per injection
Other Name: Arm B (Protocol version 6)
Experimental: Arm C
Patients with melanoma and at least one injectable lesion will receive LTX-315 to one or more lesions on two consecutive days week 1-3 in combination with ipilimumab given for 4 cycles every 3 weeks.
Drug: LTX-315 + ipilimumab
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
Other Name: Arm C (Protocol version 6)
Experimental: Arm D
Patients with TNBC and at least one injectable lesion will receive LTX-315 to one or more lesions on two consecutive days week 1-3 in combination with pembrolizumab given every 3 weeks.
Drug: LTX-315 + pembrolizumab
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
Other Name: Arm D (Protocol version 6)
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.
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:
- Safety parameters including blood samples and cardiovascular effects
- Immunohistology and ultrasound confirmation of necrosis and tumour infiltrating lymphocytes
- Systemic inflammatory response
- Evidence of clinical responses
Cohorts may be utilized to:
- Evaluate different doses of LTX-315
- Explore potential modifications to the dosing schedule
- Evaluate the potential to include appropriate combination therapies with LTX-315
- Gain further information on clinical efficacy
Please refer to this study by its ClinicalTrials.gov identifier: NCT01986426
|Contact: Andrew Saunders, MDemail@example.com|
|Contact: Berit Nicolaisenfirstname.lastname@example.org|
|Jules Bordet Institute||Recruiting|
|Bruxelles, Belgium, 1000|
|Contact: Maureen Billiet, RN +32 2 541 3303 email@example.com|
|Principal Investigator: Ahmed Awada, MD, PhD|
|Cliniques Universitaires St-Luc, Service d'oncologie médicale||Recruiting|
|Bruxelles, Belgium, 1200|
|Contact: Beatrice Vanderelst, RN +32 2 7641299 firstname.lastname@example.org|
|Principal Investigator: Jean-Francois Baurain, MD PhD|
|Paris, France, 75248|
|Contact: Anne Blondel +33 14432 4686 email@example.com|
|Principal Investigator: Christophe Le Tourneau, MD PhD|
|Sub-Investigator: Delphine Loirat, MD PhD|
|Institute Gustave Roussy||Recruiting|
|Paris, France, 94805|
|Contact: Siham Farhane, RN +33 142115 098|
|Principal Investigator: Aurelien Marabelle, MD. Ph. D|
|Intotuto Europeo di Oncologia (IEO)||Active, not recruiting|
|Milano, Italy, 20141|
|San Raffaele Hospital||Not yet recruiting|
|Milano, Italy, 20141|
|Intituto Nazionale dei Tumori||Recruiting|
|Napoli, Italy, 80131|
|Principal Investigator: Paolo Ascierto, MD PhD|
|Instituto Oncologico Venneto (IOV)||Recruiting|
|Padova, Italy, 35128|
|Principal Investigator: Vanna C Sileni, MD PhD|
|Haukeland University Hospital||Recruiting|
|Bergen, Norway, 5021|
|Contact: Mari Holsen, RN +47 55972890 firstname.lastname@example.org|
|Principal Investigator: Dag E Joessang, MD|
|Sub-Investigator: Bjorn T Gjertsen, MD Ph D|
|Oslo University Hospital Radiumhospitalet||Recruiting|
|Oslo, Norway, 0379|
|Contact: Paal Fr Brunsvig, MD PhD +47 22934000 email@example.com|
|Principal Investigator: Paal Fr Brunsvig, MD PhD|
|London, United Kingdom, SE1 9RT|
|Principal Investigator: James Spicer, MD, PhD|
|Royal Marsden Hospital||Active, not recruiting|
|London, United Kingdom, SW3 6JJ|
|University College of London Hospital||Recruiting|
|London, United Kingdom, WC 1E|
|Contact: Hazel Muteweri, RN +44 20 3447 6032 firstname.lastname@example.org|
|Principal Investigator: Rebecca Kristeleit, MD Ph. D|
|Christie Hospital NHS Foundatin Trust||Recruiting|
|Manchester, United Kingdom, M20 4BX|
|Principal Investigator: Anne Armstrong, MD PhD|
|Principal Investigator:||James Spicer, MD, PhD||Guy's Hospital|