LTX-315 and Adoptive T-cell Therapy in Advanced Soft Tissue Sarcoma (ATLAS-IT-04)

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)

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.

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