LTX-315 and Adoptive T-cell Therapy in Advanced Soft Tissue Sarcoma (ATLAS-IT-04)
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LTX-315 plus TIL infusion LTX-315 intratumoural 5mg per injection time point (number of injections per dosing days is dependent upon lesion size), TILs expansion and infusion. |
Combination Product: LTX-315 and TILs
Intratumoural injection of LTX-315 and infusion of TILs
|
Outcome Measures
Primary Outcome Measures
- Quantification of T-cell level in injected tumour tissue [Up to 10 weeks]
Evaluate ability of LTX-315 to induce T-cell infiltration
- Adverse Event Profile [Up to 15months]
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 [Up to 10 weeks]
To determine degree of T-cell infiltration of non-injected lesion following LTX-315 injection
- CD8+ T-cell expansion [Up to 10 weeks]
To assess the ability of LTX-315 to expand CD8+ T-cells from tumour tissue
- Response Rates [To 15 months]
To assess anti tumour effect of LTX-315 as part of adoptive transfer T-cell therapy by ORR, CBR and PFS
Other Outcome Measures
- Tumour specific T cells in tumour tissue and peripheral blood [To 15 months]
Tumour antigen specificity
Eligibility Criteria
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
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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
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Known to test positive for HIV/AIDs, syphilis, human T-cell leukemia-lymphoma virus, active Epstein Barr, hepatitis B or C.
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history of cerebro- or cardio-vascular disorders and would be of partcular risk of sequelae following a hypotensive episode
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If of child bearing potential, not willing to use effective form of contraception
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Breastfeeding and/or have a positive pregnancy test
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Donate sperm from start to 3 months after study treatment
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Expected to need any other anticancer treatment or immunotherapy during the treatment period
-
Clinically active or unstable central nervous system metastases
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Herlev Hospital | Copenhagen | Denmark | DK-2730 |
Sponsors and Collaborators
- Lytix Biopharma AS
- Herlev Hospital
Investigators
- Principal Investigator: Inge Marie Svane, MD, Herlev Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ATLAS-IT-04