LTX-315 and Adoptive T-cell Therapy in Advanced Soft Tissue Sarcoma (ATLAS-IT-04)
Primary Purpose
Soft Tissue Sarcoma
Status
Unknown status
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
LTX-315 and TILs
Sponsored by
About this trial
This is an interventional treatment trial for Soft Tissue Sarcoma
Eligibility Criteria
Inclusion Criteria:
- Advanced/metastatic soft tissue sarcoma that is stable or has progressed on or after minimum 1 line of systemic treatment of advanced/metastatic disease
- At least 1 index lesion accessible for injection
- At least 1 measurable non-injected lesion that can be used for response willing to undergo repeat biopsy and tumour resection procedures
- Age between 18 and 75 years
- ECOG performance status of 0-1
- Meet following blood laboratory criteria: ANC >/= 1.5, Platelet count >/=75, - Haemoglobin >/=6mmol/L, AST and ALT </=2.5 x ULN, Creatinine </=1.5 ULN
- Willing to comply with the protocol requirements and follow-up
- Signed informed consent
Exclusion Criteria:
- A history of clinically significant active systemic autoimmune disease requiring anti inflammatory or immunosuppressive therapy within the last 3 months
- Other active malignancy within the previous 5 years except for carcinoma in situ of cervix, ductal r lobular carcinoma in situ of the breast
- Received an investigational drug within 4 weeks prior to receipt of study drug
- Received external radiotherapy or cytotoxic chemotherapy within 4 weeks prior to LTX-315 administration or have not recovered from AEs (to</= grade 1) Palliative radiotherapy to non target and lesions planned for LTX-315 injection within 4 weeks of LTX-315 administration is allowed
- Currently taking any agent with a known effect on the immune system. Stable doses of corticosteroids(up to 10mg prednisolone or equivalent) are permitted for at least 2 weeks prior to LTX-315 administration
- Any serious illness or medical condition such, but not limited to: uncontrolled infection or infection requiring antibiotics, uncontrolled cardiac failure, uncontrolled systemic and gastrointestinal inflammatory conditions, bone marrow dysplasia
- Known to test positive for HIV/AIDs, syphilis, human T-cell leukemia-lymphoma virus, active Epstein Barr, hepatitis B or C.
- history of cerebro- or cardio-vascular disorders and would be of partcular risk of sequelae following a hypotensive episode
- If of child bearing potential, not willing to use effective form of contraception
- Breastfeeding and/or have a positive pregnancy test
- Donate sperm from start to 3 months after study treatment
- Expected to need any other anticancer treatment or immunotherapy during the treatment period
- Clinically active or unstable central nervous system metastases
Sites / Locations
- Herlev Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LTX-315 plus TIL infusion
Arm Description
LTX-315 intratumoural 5mg per injection time point (number of injections per dosing days is dependent upon lesion size), TILs expansion and infusion.
Outcomes
Primary Outcome Measures
Quantification of T-cell level in injected tumour tissue
Evaluate ability of LTX-315 to induce T-cell infiltration
Adverse Event Profile
Evaluate safety of LTX-315 as part of the adoptive T-cell therapy throughout treatment period
Secondary Outcome Measures
Change in T-cell level from baseline in non-injected tumour tissue
To determine degree of T-cell infiltration of non-injected lesion following LTX-315 injection
CD8+ T-cell expansion
To assess the ability of LTX-315 to expand CD8+ T-cells from tumour tissue
Response Rates
To assess anti tumour effect of LTX-315 as part of adoptive transfer T-cell therapy by ORR, CBR and PFS
Full Information
NCT ID
NCT03725605
First Posted
October 2, 2018
Last Updated
August 27, 2021
Sponsor
Lytix Biopharma AS
Collaborators
Herlev Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03725605
Brief Title
LTX-315 and Adoptive T-cell Therapy in Advanced Soft Tissue Sarcoma (ATLAS-IT-04)
Official Title
An Open Label Phase II Single Centre Study Investigating the Safety and Efficacy of LTX-315 and Adoptive T-cell Therapy in Patients With Advanced/Metastatic Soft Tissue Sarcoma (ATLAS-IT-04)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Unknown status
Study Start Date
December 28, 2018 (Actual)
Primary Completion Date
February 2023 (Anticipated)
Study Completion Date
February 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lytix Biopharma AS
Collaborators
Herlev Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
ATLAS-IT-04 is a two part, single arm study designed to determine the safety and effectiveness of LTX-315 to induce T-cell infiltration prior to TIL expansion in patients with soft tissue sarcoma. Following intratumoural injection of LTX-315 to a selected lesion, the lesion will be extracted for T-cell culture, expansion and infusion.
Detailed Description
Patients with advanced/metastatic tumours who have received at least one approved standard of care treatment will be recruited. All patients must have at least two lesions, one that can injected with LTX-315 and another that can used to assess response. In the first part of the study, LTX-315 will be administered intratumorally on 4-6 dosing days over a 2-4 week period to an index lesion which will be biopsied or removed after treatment for T-cell expansion. The second part will involve culturing and expanding T-cells for infusion of tumour infiltrating lymphocytes (TILs) following an induction regimen. The safety and efficacy of the LTX-315 and TIL treatment will be assessed. Patients will be followed up for 15 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
LTX-315 and TILs
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
LTX-315 plus TIL infusion
Arm Type
Experimental
Arm Description
LTX-315 intratumoural 5mg per injection time point (number of injections per dosing days is dependent upon lesion size), TILs expansion and infusion.
Intervention Type
Combination Product
Intervention Name(s)
LTX-315 and TILs
Intervention Description
Intratumoural injection of LTX-315 and infusion of TILs
Primary Outcome Measure Information:
Title
Quantification of T-cell level in injected tumour tissue
Description
Evaluate ability of LTX-315 to induce T-cell infiltration
Time Frame
Up to 10 weeks
Title
Adverse Event Profile
Description
Evaluate safety of LTX-315 as part of the adoptive T-cell therapy throughout treatment period
Time Frame
Up to 15months
Secondary Outcome Measure Information:
Title
Change in T-cell level from baseline in non-injected tumour tissue
Description
To determine degree of T-cell infiltration of non-injected lesion following LTX-315 injection
Time Frame
Up to 10 weeks
Title
CD8+ T-cell expansion
Description
To assess the ability of LTX-315 to expand CD8+ T-cells from tumour tissue
Time Frame
Up to 10 weeks
Title
Response Rates
Description
To assess anti tumour effect of LTX-315 as part of adoptive transfer T-cell therapy by ORR, CBR and PFS
Time Frame
To 15 months
Other Pre-specified Outcome Measures:
Title
Tumour specific T cells in tumour tissue and peripheral blood
Description
Tumour antigen specificity
Time Frame
To 15 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Advanced/metastatic soft tissue sarcoma that is stable or has progressed on or after minimum 1 line of systemic treatment of advanced/metastatic disease
At least 1 index lesion accessible for injection
At least 1 measurable non-injected lesion that can be used for response willing to undergo repeat biopsy and tumour resection procedures
Age between 18 and 75 years
ECOG performance status of 0-1
Meet following blood laboratory criteria: ANC >/= 1.5, Platelet count >/=75, - Haemoglobin >/=6mmol/L, AST and ALT </=2.5 x ULN, Creatinine </=1.5 ULN
Willing to comply with the protocol requirements and follow-up
Signed informed consent
Exclusion Criteria:
A history of clinically significant active systemic autoimmune disease requiring anti inflammatory or immunosuppressive therapy within the last 3 months
Other active malignancy within the previous 5 years except for carcinoma in situ of cervix, ductal r lobular carcinoma in situ of the breast
Received an investigational drug within 4 weeks prior to receipt of study drug
Received external radiotherapy or cytotoxic chemotherapy within 4 weeks prior to LTX-315 administration or have not recovered from AEs (to</= grade 1) Palliative radiotherapy to non target and lesions planned for LTX-315 injection within 4 weeks of LTX-315 administration is allowed
Currently taking any agent with a known effect on the immune system. Stable doses of corticosteroids(up to 10mg prednisolone or equivalent) are permitted for at least 2 weeks prior to LTX-315 administration
Any serious illness or medical condition such, but not limited to: uncontrolled infection or infection requiring antibiotics, uncontrolled cardiac failure, uncontrolled systemic and gastrointestinal inflammatory conditions, bone marrow dysplasia
Known to test positive for HIV/AIDs, syphilis, human T-cell leukemia-lymphoma virus, active Epstein Barr, hepatitis B or C.
history of cerebro- or cardio-vascular disorders and would be of partcular risk of sequelae following a hypotensive episode
If of child bearing potential, not willing to use effective form of contraception
Breastfeeding and/or have a positive pregnancy test
Donate sperm from start to 3 months after study treatment
Expected to need any other anticancer treatment or immunotherapy during the treatment period
Clinically active or unstable central nervous system metastases
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Inge Marie Svane, MD
Organizational Affiliation
Herlev Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Herlev Hospital
City
Copenhagen
ZIP/Postal Code
DK-2730
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
LTX-315 and Adoptive T-cell Therapy in Advanced Soft Tissue Sarcoma (ATLAS-IT-04)
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