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

Phase 2

Completed

Conditions: Soft Tissue Sarcoma

Interventions: Combination Product: LTX-315 and TILs

Registration Number: NCT03725605

Lead Sponsor: Lytix Biopharma AS

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 6

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LTX-315 plus TIL infusion	LTX-315 and TILs	LTX-315 intratumoural injection, TILs expansion and infusion.

Primary Outcome Measures

Name	Time	Method
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)	15 to 42 days	The total T-cell level was measured at baseline and end of Step 1. Change from baseline was listed as absolute change. Data cannot be presented on subject-level and are therefore presented as the arithmetic mean value for the factor increase (+) or decrease (-) in number of cells/mm2 from baseline to end of Step 1.
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)	Up to 133 days	AEs were events occurring during or after administration of the IMP. AEs were coded using MedDRA version 21.1 and were classified by System Organ Class (SOC), Preferred Term (PT) and Lowest Level Term (LLT). Adverse events related to LTX-315 were events where causality to LTX-315 was marked on the adverse events page. Adverse events related to the combination of LTX-315 and adoptive T-cell therapy were events where both causality to LTX-315 and at least one of the other IMPs (TILs, Sendoxan®, Fludara® and Proleukin®) were marked on the adverse event page.

Secondary Outcome Measures

Name	Time	Method
% CD3+CD8+ T-cells of Total CD3+ in TIL Infusion Product	41 to 49 days between Step 1 and Step 2	The composition of the TIL infusion product was evaluated for the subjects for whom it was possible to grow TILs.
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)	Up to 133 days	The change is described as factor change in CD8+ cells/mm2.
Total Number of CD3+CD8+ T-cells in TIL Infusion Product	41 to 49 days between Step 1 and Step 2	The composition of the TIL infusion product was evaluated for the subjects for whom it was possible to grow TILs.
Objective Response Rate	EoT (Step 2, Week 7) and up to 15 months after EoT.	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Clinical Benefit Rate	Up to 15 months	The clinical benefit rate (CBR) was defined as proportion of subjects who according to RECIST 1.1 had achieved complete response, partial response or stable disease at EoT (Step 2, Week 7) and up to 15 months after EoT. CBR was evaluated at Step 2, Week 7 and Week 13.
Best Overall Tumour Response Rate	Assessed at Visit 25 (Step 2, Week 7, Day 42)	Best overall tumour response rate (BOR) was defined in the CSP as the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started).
Progression Free Survival	Days from screening (Baseline) until date of progressive disease or up to 15 months after EoT.	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.