AzTrials
AzTrials

CancerPhase 1NCT01986426

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

A Phase 1 study testing LTX-315 consecutive lesions, LTX-315 and LTX-315 + ipilimumab in people with Cancer and Melanoma, run by Lytix Biopharma AS at 14 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer, Melanoma, Breast Cancer
What is being tested?
LTX-315 consecutive lesions, LTX-315 and LTX-315 + ipilimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
14 sitesin 5 countries
Study dates
Nov 2013to 31 Aug 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 25Show fewer
  • 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:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Absolute lymphocyte count ≥ 0.8 x 109/L
  • Platelet count ≥ 75 x 109/L
  • Haemoglobin ≥ 9.0 g/dL
  • aPTT/PT within the institution's normal range
  • Total bilirubin level ≤ 1.5 x ULN
  • ASAT and ALAT ≤ 2.5 x ULN (≤5 x ULN if liver metastasis present)
  • Creatinine ≤ 1.5 x ULN
  • Albumin ≥ 30 g/L

Who cannot join

  • 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.
Show all 22Show fewer
  • 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:
  • Uncontrolled infection or infection requiring antibiotics
  • Uncontrolled cardiac failure: Classification III or IV (New York Heart Association)
  • Uncontrolled systemic and gastro-intestinal inflammatory conditions
  • 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.

Trial locations and contacts

14 sites in 5 countries.

14 sites in 5 countries

Italy4 sites

  • Intotuto Europeo di Oncologia (IEO)

    Milan, 20141

  • San Raffaele Hospital

    Milan, 20141

  • Intituto Nazionale dei Tumori

    Naples, 80131

  • Instituto Oncologico Venneto (IOV)

    Padova, 35128

Other trials in Italy

United Kingdom4 sites

  • Guy's Hospital

    London, SE1 9RT

  • Royal Marsden Hospital

    London, SW3 6JJ

  • University College of London Hospital

    London, WC 1E

  • Christie Hospital NHS Foundatin Trust

    Manchester, M20 4BX

Other trials in United Kingdom

Belgium2 sites

  • Jules Bordet Institute

    Brussels, 1000

  • Cliniques Universitaires St-Luc, Service d'oncologie médicale

    Brussels, 1200

Other trials in Belgium

France2 sites

  • Institut Curie

    Paris, 75248

  • Institute Gustave Roussy

    Paris, 94805

Other trials in France

Norway2 sites

  • Haukeland University Hospital

    Bergen, 5021

  • Oslo University Hospital Radiumhospitalet

    Oslo, 0379

Other trials in Norway

About this study

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

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.

Read the 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
Being tested
LTX-315 consecutive lesions, LTX-315, LTX-315 + ipilimumab, LTX-315 + pembrolizumab
Keywords
Transdermal accessible tumours
Medical subject headings
Neoplasms, Melanoma, Breast Neoplasms, Head and Neck Neoplasms, Lymphoma, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LTX-315 consecutive lesionsDrug

    Also called Protocol version 4

    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)

  • LTX-315Drug

    Also called Arm B (Protocol version 6)

    Dose escalation:

    Cohort 1: 3 mg per injection Cohort 2: 4 mg per injection Cohort 3: 5 mg per injection

  • LTX-315 + ipilimumabDrug

    Also called Arm C (Protocol version 6)

    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

  • LTX-315 + pembrolizumabDrug

    Also called Arm D (Protocol version 6)

    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

Study groups in NCT01986426
Study groupRoleWhat they receive
Arm A: LTX-315 monotherapy singe lesionExperimentalCohort 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.
Receives: Drug: LTX-315 consecutive lesions
Arm B: LTX-315 monotherapy in multiple concurrent lesionsExperimentalPatients 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.
Receives: Drug: LTX-315
Arm CExperimentalPatients 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.
Receives: Drug: LTX-315 + ipilimumab
Arm DExperimentalPatients 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.
Receives: Drug: LTX-315 + pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 21 days

Secondary outcomes (5)

  1. Anti tumour activity in injected tumour

    Number of patients with regression of injected tumour assessed by ultrasound and/or CT/MRI.

    Measured: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed

  2. Complete response (irCR) and partial response (irPR)

    Number of patients by irRC

    Measured: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed

  3. Overall response rate (OR)

    (irRC criteria)

    Measured: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed

  4. Disease control rate (CR + PR + SD)

    irRC criteria

    Measured: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed

  5. Progression free survival (PFS)

    irRC criteria

    Measured: Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Nov 2013 (estimated)
  2. Study startNov 2013
  3. Primary completionApr 2018
  4. Study completion31 Aug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01986426
Sponsor's protocol ID
C12-315-03
Status last verified
May 2018
First submitted
28 Oct 2013
Last updated
3 Oct 2018
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Spicer J, Marabelle A, Baurain JF, Jebsen NL, Jossang DE, Awada A, Kristeleit R, Loirat D, Lazaridis G, Jungels C, Brunsvig P, Nicolaisen B, Saunders A, Patel H, Galon J, Hermitte F, Camilio KA, Mauseth B, Sundvold V, Sveinbjornsson B, Rekdal O. Safety, Antitumor Activity, and T-cell Responses in a Dose-Ranging Phase I Trial of the Oncolytic Peptide LTX-315 in Patients with Solid Tumors. Clin Cancer Res. 2021 May 15;27(10):2755-2763. doi: 10.1158/1078-0432.CCR-20-3435. Epub 2021 Feb 4.

    PubMed 33542073

  • Jebsen NL, Apelseth TO, Haugland HK, Rekdal O, Patel H, Gjertsen BT, Jossang 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.

    PubMed 31177991

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LTX-315 consecutive lesions, LTX-315 and LTX-315 + ipilimumab in people with Cancer and Melanoma, run by Lytix Biopharma AS at 14 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Italy, United Kingdom, Belgium, France, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity (time frame: 21 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01986426, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2018; AzTrials last refreshed its copy on 7 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in