Clinical trial NCT03725605: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Soft Tissue Sarcoma
Lead sponsor: Lytix Biopharma AS
Sponsor class: INDUSTRY
Collaborators: name: Herlev Hospital
First posted: 2018-10-31
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: LTX-315 and TILs
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Total T-cell Level in Tumour Tissues From Baseline (Step 1, Week 1, Day 1) to End of Step 1 (Step 1, Week 3-5)
timeFrame: 15 to 42 days
measure: Adverse Events (AE) Related to LTX-315 or to the Combination of LTX-315 and Adoptive T-cell Therapy From Baseline (Step 1, Week 1, Day 1) to End of Treatment (EoT) (Step 2, Week 7)
timeFrame: Up to 133 days
Secondary outcomes:
measure: Change in CD3+CD8+ T Cell Density in Non-injected Tumour Tissues From Baseline (Step 1, Week 1, Day 1) to EoT (Step 2, Week 7)
timeFrame: Up to 133 days
measure: Total Number of CD3+CD8+ T-cells in TIL Infusion Product
timeFrame: 41 to 49 days between Step 1 and Step 2
measure: % CD3+CD8+ T-cells of Total CD3+ in TIL Infusion Product
timeFrame: 41 to 49 days between Step 1 and Step 2
measure: Objective Response Rate
timeFrame: EoT (Step 2, Week 7) and up to 15 months after EoT.
measure: Clinical Benefit Rate
timeFrame: Up to 15 months
measure: Best Overall Tumour Response Rate
timeFrame: Assessed at Visit 25 (Step 2, Week 7, Day 42)
measure: Progression Free Survival
timeFrame: Days from screening (Baseline) until date of progressive disease or up to 15 months after EoT.
Other outcomes:
measure: Number of Participants With Tumour-antigen Specific T-cells in Tumour Tissue and Peripheral Blood Mononuclear Cells
timeFrame: Up to 15 months
measure: Changes in Immunological Parameters From Baseline (Step 1, Week 1, Day 1) to 15 Months After EoT
timeFrame: Up to 15 months
Locations:
city: Copenhagen
country: Denmark
facility: Herlev Hospital
Study officials:
affiliation: Herlev Hospital
name: Inge Marie Svane, MD
role: PRINCIPAL_INVESTIGATOR
References: