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

NCT01986426 | Completed Phase 1

• 1 other identifier: C12-315-03
• Study Type: interventional
• Target: 80
• Locations: 5 countries
• Sites: 14

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.

Conditions

Cancer; Melanoma; Breast Cancer; Head and Neck Cancer; Lymphoma; Triple-Negative Breast Cancer

Keywords

Transdermal accessible tumours

Outcome Measures

Primary Outcomes (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.

  21 days

Secondary Outcomes (5)

• Anti tumour activity in injected tumour

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

• Complete response (irCR) and partial response (irPR)

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

• Overall response rate (OR)

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

• Disease control rate (CR + PR + SD)

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

• Progression free survival (PFS)

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

Other Outcomes (1)

• Pharmacokinetic (PK) profile of LTX-315

  Pre and 1 hour post dosing Day 2 Week 1

Study Arms (4)

Arm A: LTX-315 monotherapy singe lesion

EXPERIMENTAL

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

Arm B: LTX-315 monotherapy in multiple concurrent lesions

EXPERIMENTAL

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

Arm C

EXPERIMENTAL

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

Arm D

EXPERIMENTAL

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

Interventions

LTX-315 consecutive lesions DRUG

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)

Also known as: Protocol version 4

Arm A: LTX-315 monotherapy singe lesion

LTX-315 DRUG

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

Also known as: Arm B (Protocol version 6)

Arm B: LTX-315 monotherapy in multiple concurrent lesions

LTX-315 + ipilimumab DRUG

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

Also known as: Arm C (Protocol version 6)

Arm C

LTX-315 + pembrolizumab DRUG

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

Also known as: Arm D (Protocol version 6)

Arm D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• Lytix Biopharma AS: lead
• Theradex: collaborator
• ICON plc: collaborator

Study Sites (14)

Jules Bordet Institute

Brussels, 1000, Belgium

Location

Cliniques Universitaires St-Luc, Service d'oncologie médicale

Brussels, 1200, Belgium

Location

Institut Curie

Paris, 75248, France

Location

Institute Gustave Roussy

Paris, 94805, France

Location

Intotuto Europeo di Oncologia (IEO)

Milan, 20141, Italy

Location

San Raffaele Hospital

Milan, 20141, Italy

Location

Intituto Nazionale dei Tumori

Napoli, 80131, Italy

Location

Instituto Oncologico Venneto (IOV)

Padua, 35128, Italy

Location

Haukeland University Hospital

Bergen, 5021, Norway

Location

Oslo University Hospital Radiumhospitalet

Oslo, 0379, Norway

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

University College of London Hospital

London, WC 1E, United Kingdom

Location

Christie Hospital NHS Foundatin Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 33542073 DERIVED

• 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.

  PMID: 31177991 DERIVED

MeSH Terms

Conditions

Neoplasms; Melanoma; Breast Neoplasms; Head and Neck Neoplasms; Lymphoma; Triple Negative Breast Neoplasms

Interventions

LTX-315; Ipilimumab; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Breast Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• James Spicer, MD, PhD

  Guy's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2013
• First Posted: November 18, 2013
• Study Start: November 1, 2013
• Primary Completion: April 1, 2018
• Study Completion: August 31, 2018
• Last Updated: October 3, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

NO (2); GB (4); BE (2); FR (2); IT (4)