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

Soft Tissue Sarcoma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03725605
• Other study ID #: C17-315-04 (ATLAS-IT-04)
• Status: Completed
• Phase: Phase 2
• Start date: December 28, 2018
• Est. completion date: October 11, 2021

Study information

• Verified date: November 2023
• Source: Lytix Biopharma AS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: October 11, 2021
• Est. primary completion date: July 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Sarcoma
• Soft Tissue Sarcoma

Intervention

Combination Product:
• LTX-315 and TILs
Intratumoural injection of LTX-315 and infusion of TILs

Locations

Country	Name	City	State
Denmark	Herlev Hospital	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Lytix Biopharma AS	Herlev Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Tumour-antigen Specific T-cells in Tumour Tissue and Peripheral Blood Mononuclear Cells	Tumour-antigen Specific T-cells in Tumour Tissue and Peripheral Blood Mononuclear Cells antigen specificity assessed by enzyme-linked immuno-spot assay (ELISPOT) and flowcytometry analysis of cytokines including interferon gamma (IFN?) and tumour necrosis factor alpha (TNF?)	Up to 15 months
Other	Changes in Immunological Parameters From Baseline (Step 1, Week 1, Day 1) to 15 Months After EoT	Systemic immune effect of the treatment was assessed by sequencing the TCR repertoire in the peripheral blood mononuclear cells (PBMCs), the TIL product and the biopsies. The outcome of this endpoint is described as the number of subjects for whom a systemic immune effect (in terms of expansion of a significant number of T-cell clones in the blood) was observed.	Up to 15 months
Primary	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)	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.	15 to 42 days
Primary	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)	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.	Up to 133 days
Secondary	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)	The change is described as factor change in CD8+ cells/mm2.	Up to 133 days
Secondary	Total Number of CD3+CD8+ T-cells in TIL Infusion Product	The composition of the TIL infusion product was evaluated for the subjects for whom it was possible to grow TILs.	41 to 49 days between Step 1 and Step 2
Secondary	% CD3+CD8+ T-cells of Total CD3+ in TIL Infusion Product	The composition of the TIL infusion product was evaluated for the subjects for whom it was possible to grow TILs.	41 to 49 days between Step 1 and Step 2
Secondary	Objective Response Rate	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.	EoT (Step 2, Week 7) and up to 15 months after EoT.
Secondary	Clinical Benefit Rate	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.	Up to 15 months
Secondary	Best Overall Tumour Response Rate	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).	Assessed at Visit 25 (Step 2, Week 7, Day 42)
Secondary	Progression Free Survival	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.	Days from screening (Baseline) until date of progressive disease or up to 15 months after EoT.