ltx-315 and adoptive t-cell therapy in advanced soft tissue sarcoma (atlas-it-04)

Conditions: Soft Tissue Sarcoma

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.

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.

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 particular 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