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Trial record 3 of 3 for:    LTX-315

LTX-315 in Patients With Transdermally Accessible Tumours as Monotherapy or Combination With Ipilimumab or Pembrolizumab

This study is currently recruiting participants.
See Contacts and Locations
Verified March 2017 by Lytix Biopharma AS
Sponsor:
Collaborators:
Theradex
ICON plc
Information provided by (Responsible Party):
Lytix Biopharma AS
ClinicalTrials.gov Identifier:
NCT01986426
First received: October 28, 2013
Last updated: March 30, 2017
Last verified: March 2017
  Purpose
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.

Condition Intervention Phase
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 Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Lytix Biopharma AS:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Other Outcome Measures:
  • 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.


Estimated Enrollment: 80
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)
Arms Assigned Interventions
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

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)

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.

Drug: LTX-315

Dose escalation:

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)

Detailed Description:

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
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Arm A: (Recruitment completed)

Arm B:

  • Unresectable metastatic disease (any tumor type) and conventional anti-tumor treatment is not appropriate.
  • Have at least one available lesion (cutaneous, sub-cutaneous, oral or lymph node) for injection between 1-3 cm longest diameter and one bystander lesion (non-injected).

Arm C:

  • Have unresectable/metastatic diagnosis of malignant melanoma (histologically confirmed).
  • Have at least one available lesion (cutaneous, sub-cutaneous, oral or lymph node) for injection and biopsy which is between 1 and 3 cm in longest diameter.
  • Have had previous treatment with an anti-PD-1 antibody (as monotherapy or as part of combination (any combination) as 1st or 2nd line metastatic treatment).

Arm D:

  • Have unresectable/metastatic diagnosis of triple negative breast cancer (histologically confirmed).
  • Have at least one available lesion (cutaneous, sub-cutaneous or lymph node) for injection and biopsy with a minimum longest diameter of 1 cm.
  • Have received between one and 4 prior systemic treatments for metastatic triple negative breast cancer.

All arms:

  • Be willing to undergo repeat tumour biopsy and/or tumour resection procedures.
  • Have an ECOG Performance status (PS): 0 - 1.
  • Meet the following laboratory requirements:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    2. Absolute lymphocyte count ≥ 0.8 x 109/L
    3. Platelet count ≥ 75 x 109/L
    4. Haemoglobin ≥ 9.0 g/dL
    5. aPTT/PT within the institution's normal range
    6. Total bilirubin level ≤ 1.5 x ULN
    7. ASAT and ALAT ≤ 2.5 x ULN (≤5 x ULN if liver metastasis present)
    8. Creatinine ≤ 1.5 x ULN
    9. Albumin ≥ 30 g/L

      Exclusion Criteria:

      Arm A: (Completed)

      Arm B:

  • Have a history of systemic auto-immune disease requiring anti-inflammatory or immunosuppressive therapy within the last 3 months. Patients with history of autoimmune thyroiditis are eligible provided the patient requires only thyroid hormone replacement therapy and disease has been stable for ≥ 1 year.

Arm C:

  • Have had prior therapy with ipilimumab or any other anti-CTLA-4 monoclonal antibody.
  • Have had BRAF/MEK inhibitors administered within 2 weeks prior to the study drug administration.
  • Have active systemic autoimmune disease; have had prior pneumonitis; have a history of severe hypersensitivity to another monoclonal antibody; are receiving immunosuppressive therapy; have a history of severe immune-related adverse reaction from treatment with a monoclonal antibody, defined as any Grade 4 or 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for greater than 12 weeks.

Arm D:

  • Have had prior therapy with an anti-PD-1 or anti-PD-L1 monoclonal antibody.
  • Have received cancer immunotherapy within 2 weeks prior to study drug administration or have not recovered from adverse events (to ≤ CTCAE grade 1) due to such agents.
  • Have active systemic autoimmune disease; have had prior pneumonitis; have a history of severe hypersensitivity to another monoclonal antibody; are receiving immunosuppressive therapy; and have a history of severe immune-related adverse reactions from treatment with a monoclonal antibody, defined as any Grade 4 or 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for greater than 12 weeks.

All arms:

  • Have received external radiotherapy or cytotoxic chemotherapy within 4 weeks prior to study drug administration, or have not recovered from adverse events (≤ CTCAE grade 1) due to agents administered more than 4 weeks earlier. Palliative radiotherapy to non-target lesions within 4 weeks prior to study drug administration is allowed.
  • Are currently taking any agent with a known effect on the immune system. Patients are allowed to be on a stable dose of corticosteroids (up to 10 mg daily prednisolone or equivalent) for at least 2 weeks prior to study drug administration (please see Appendix IV for prohibited medications).
  • Have any other serious illness or medical condition such as, but not limited to:

    1. Uncontrolled infection or infection requiring antibiotics
    2. Uncontrolled cardiac failure: Classification III or IV (New York Heart Association)
    3. Uncontrolled systemic and gastro-intestinal inflammatory conditions
    4. Bone marrow dysplasia
  • Have a known history of positive tests for HIV/AIDS, or have active hepatitis B or C (based on serology).
  • Are expected to need any other anti-cancer therapy or immunotherapy to be initiated during the study period.

    15. Have clinically active or unstable CNS metastases as assessed by the treating physician.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01986426

Contacts
Contact: Andrew Saunders, MD andrew.saunders@lytixbiopharma.com
Contact: Berit Nicolaisen berit.nicolaisen@lytixbiopharma.com

Locations
Belgium
Jules Bordet Institute Recruiting
Bruxelles, Belgium, 1000
Contact: Maureen Billiet, RN    +32 2 541 3303    maureen.billiet@bordet.be   
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    beatrice.vanderelst@uclouvain.be   
Principal Investigator: Jean-Francois Baurain, MD PhD         
France
Institut Curie Recruiting
Paris, France, 75248
Contact: Anne Blondel    +33 14432 4686    anne.blondel@curie.fr   
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         
Italy
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         
Norway
Haukeland University Hospital Recruiting
Bergen, Norway, 5021
Contact: Mari Holsen, RN    +47 55972890    mari.helgesen.holsen@helse-bergen.no   
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    pfb@ous-hf.no   
Principal Investigator: Paal Fr Brunsvig, MD PhD         
United Kingdom
Guy's Hospital Recruiting
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    hazel.muteweri@uclh.nhs.uk   
Principal Investigator: Rebecca Kristeleit, MD Ph. D         
Christie Hospital NHS Foundatin Trust Recruiting
Manchester, United Kingdom, M20 4BX
Principal Investigator: Anne Armstrong, MD PhD         
Sponsors and Collaborators
Lytix Biopharma AS
Theradex
ICON plc
Investigators
Principal Investigator: James Spicer, MD, PhD Guy's Hospital
  More Information

Responsible Party: Lytix Biopharma AS
ClinicalTrials.gov Identifier: NCT01986426     History of Changes
Other Study ID Numbers: C12-315-03
Study First Received: October 28, 2013
Last Updated: March 30, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Lytix Biopharma AS:
Transdermal accessible tumours

Additional relevant MeSH terms:
Breast Neoplasms
Head and Neck Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Pembrolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 23, 2017