Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01986426
Recruitment Status : Completed
First Posted : November 18, 2013
Last Update Posted : October 3, 2018
Sponsor:
Collaborators:
Theradex
ICON plc
Information provided by (Responsible Party):
Lytix Biopharma AS

Tracking Information
First Submitted Date  ICMJE October 28, 2013
First Posted Date  ICMJE November 18, 2013
Last Update Posted Date October 3, 2018
Actual Study Start Date  ICMJE November 2013
Actual Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2016)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 11, 2013)
Dose limiting toxicity [ Time Frame: At each dosing timepoint up to 32 weeks ]
Dose limiting toxicities (DLT) and the overall safety profile (adverse events (AE), laboratory assessments, physical findings and symptomatic assessment) of LTX-315 will be measured at each dosing point (may be weekly) up to 32 weeks post first dosing
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2016)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2013)
Anti tumour effects [ Time Frame: First index lesion at week 7. Second index lesion week 22 and end of treatment week 32 ]
Tumour necrosis will be assessed based on ultrasound imaging and scored according to irRC.
Current Other Pre-specified Outcome Measures
 (submitted: December 20, 2016)
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.
Original Other Pre-specified Outcome Measures
 (submitted: November 11, 2013)
  • General systemic inflammatory response [ Time Frame: Week 8, week 13 week 28 and week 24 ]
    Immunological response prameters will be monitored from blood samples to investigate and characterize the immune status of the patient and the nature of the anti tumour response.
  • Local inflammatory responses [ Time Frame: Week 7 and end of treatment (Week 32) ]
    Biopsies and tumour resection samples will be collected and prepared for histological and immunohistochemical evaluation of the local inflammatory response.
 
Descriptive Information
Brief Title  ICMJE LTX-315 in Patients With Transdermally Accessible Tumours as Monotherapy or Combination With Ipilimumab or Pembrolizumab
Official Title  ICMJE 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
Brief Summary 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.
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cancer
  • Melanoma
  • Breast Cancer
  • Head and Neck Cancer
  • Lymphoma
  • Triple-Negative Breast Cancer
Intervention  ICMJE
  • 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
  • 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)
  • 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)
  • 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)
Study Arms  ICMJE
  • 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.

    Intervention: Drug: LTX-315 consecutive lesions
  • 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.

    Intervention: Drug: LTX-315
  • 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.
    Intervention: Drug: LTX-315 + ipilimumab
  • 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.
    Intervention: Drug: LTX-315 + pembrolizumab
Publications * Jebsen NL, Apelseth TO, Haugland HK, Rekdal Ø, Patel H, Gjertsen BT, Jøssang DE. Enhanced T-lymphocyte infiltration in a desmoid tumor of the thoracic wall in a young woman treated with intratumoral injections of the oncolytic peptide LTX-315: a case report. J Med Case Rep. 2019 Jun 10;13(1):177. doi: 10.1186/s13256-019-2088-6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: November 11, 2013)
80
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 31, 2018
Actual Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Italy,   Norway,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01986426
Other Study ID Numbers  ICMJE C12-315-03
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Lytix Biopharma AS
Study Sponsor  ICMJE Lytix Biopharma AS
Collaborators  ICMJE
  • Theradex
  • ICON plc
Investigators  ICMJE
Principal Investigator: James Spicer, MD, PhD Guy's Hospital
PRS Account Lytix Biopharma AS
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP