Soft tissue sarcoma MedDRA version: 20.0 Level: HLGT Classification code 10072990 Term: Soft tissue neoplasms malignant and unspecified System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: LTX-315
Pharmaceutical Form: Powder for injection
INN or Proposed INN: NA
Other descriptive name: LTX-315
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration numb
Sponsors
Lytix Biopharma AS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. (Histologically) Confirmed any patients with advanced or metastatic soft tissue sarcoma with stable disease or has progressed after a minimum of 1 systemic treatment of advanced/metastatic disease. Patient will have received at least 1 approved standard of care treatment for advanced/metastatic disease or be deemed unsuitable for such treatment by their treating physician 2. At least 1 index tumour lesion accessible for injection with a longest diameter (LD) of = 1cm which is planned for LTX-315 injection 3. At least 1 measurable (target) non-injected tumour lesion that can be used to assess response by Computed Tomography (CT-scan) (as per RECIST) 4. A life expectancy of at least 3 months 5. Willing to undergo repeat tumour biopsy and/or tumour resection procedures 6. Between 18 and 75 years of age 7. An Eastern Cooperative Oncology Group (ECOG) performance status: 0 – 1 8. Meet the following blood laboratory requirements: a. Absolute neutrophil count (ANC) = 1.5 x 109/L b. Platelet count = 75 x 109/L c. Haemoglobin = 6.0 mmol/L after blood transfusion if needed d. Prothrombin time / International Normalised Ratio (PT/INR) within the institution’s normal range e. Aspartate Transferase (AST) and Alanine Transferase (ALT) = 2.5 x upper normal level f. Creatinine = 1.5 x upper normal level 9. Willing and able to comply with the protocol and agree to return to the hospital for follow-up visits and examinations up to 15 months after EoT 10. Fully informed about the study and have signed the informed consent form 11. Re-screening is allowed once on a case by case basis as judged by the investigator Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. A history of clinical significant active systemic autoimmune disease requiring antiinflammatory or immunosuppressive therapy within the last 3 months. Patients with history of autoimmune thyroiditis are eligible provided the patient requires only thyroid hormone replacement therapy and disease has been stable for = 1 year 2. Any other malignancy active within the previous 5 years except for carcinoma in situ of the cervix, ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) of the breast 3. Received an investigational drug within 4 weeks prior to any study drug administration, or are scheduled to receive 1 during the study participation 4. Received external radiotherapy or cytotoxic chemotherapy within 4 weeks prior to LTX-315 administration, or have not recovered from AEs (to = CTCAE grade 1) due to agents administered more than 4 weeks earlier. Palliative radiotherapy to nontarget and lesions planned for LTX-315 injection within 4 weeks of LTX-315 administration is allowed 5. Currently taking any agent with a known effect on the immune system. Patients are allowed to be on a stable dose of corticosteroids (up to 10 mg daily prednisolone or equivalent) for at least 2 weeks prior to LTX-315 administration 6. Any other serious illness or medical condition such as, but not limited to: a. Uncontrolled infection or infection requiring antibiotics b. Uncontrolled cardiac failure: Classification III or IV (New York Heart Association) c. Uncontrolled systemic and gastrointestinal inflammatory conditions d. Bone marrow dysplasia 7. A known history of positive tests for HIV/AIDS, syphilis, human T-cell leukemialymphoma virus (HTLV), active Epstein-Barr, hepatitis B or C (based on serology) 8. A history of cerebrovascular or cardiac disorders and would be at particular risk of sequelae following a short hypotensive episode 9. If of child-bearing potential, not willing to use an effective form of contraception such as hormonal birth control, intrauterine device or double barrier method from screening visit and until 3 months after last study treatment (any of the agents) 10. Breastfeeding and/or have a positive pregnancy test during screening 11. Donate sperm from LTX-315 dosing until 3 months after last study treatment (any of the agents) 12. Patients with pregnant or partner of child-bearing potential not willing to use contraception from LTX-315 administration until 3 months after last study treatment (any of the agents) 13. Expected to need any other anticancer therapy or immunotherapy to be initiated during the treatment period 14. Clinically active or unstable metastases in the central nerveous system as assessed by the treating physician 15. Any known hypersensitivity to any of the excipients in the non-IMPs including the required allergic prophylactic medications (H1 and H2 antagonists, Leukotriene antagonists) 16. Any known or suspected hypersensitivity to any of the IMPs
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: * To determine the ability of LTX-315 to induce T-cell infiltration prior to TIL expansion in advanced/metastatic soft tissue sarcoma * To determine the safety of LTX-315 as part of adoptive T-cell therapy in advanced/metastatic soft tissue sarcoma;Secondary Objective: * To determine the ability of LTX-315 as part of adoptive T-cell therapy to induce T-cell infiltration in advanced/metastatic soft tissue sarcoma * To assess the ability to expand CD8+ T-cells from tumour tissues * To assess the anti-tumour effect of LTX-315 as part of adoptive T-cell therapy in advanced/metastatic soft tissue sarcoma;Primary end point(s): * 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) * 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);Timepoint(s) of evaluation of this end point: * from Baseline (Step 1, Week 1, Day 1) to end of Step 1 (Step 1, Week 3) * from Baseline (Step 1, Week 1, Day 1) to end of treatment (Step 2, Week 7) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): * Change in CD3+ T-cell and CD3+CD8+ T-cell density in non-injected tumour tissues from Baseline (Step 1, Week 1, Day 1) to EoT (Step 2, Week 7) if the patient has a feasible bystander lesion and accept it to be biopsied * Total number of CD3+CD8+ T cells and % CD3+CD8+T cells of total CD3+ T cells in final TIL infusion product * The anti-tumour effect assessed by: o Objective Response Rate (ORR) defined as proportion of patients who have achieved immune-related complete response (irCR) or immune-related partial response (irPR) at EoT (Step 2, Week 7) and up to 15 months after EoT o Clinical Benefit Rate (CBR) defined as proportion of patients who have achieved irCR, irPR or immune-related stable disease (irSD) at EoT (Step 2, Week 7) and up to 15 months after EoT o Progression free survival (PFS) evaluated by time from Baseline until immunerelated progressive disease (irPD) or death up to 15 months after EoT;Timepoint(s) of evaluation of this end point: * from Baseline (Step 1, Week 1, Day 1) to EoT (Step 2, Week 7) * from Baseline (Step 1, Week 1, Day 1) to end of Step 1 (Step 1, Week 3) and EoT (Step 2, Week 7) * at EoT (Step 2, Week 7) and up to 15 months after EoT * at EoT (Step 2, Week 7) and up to 15 months after EoT * from Baseline until immunerelated progressive disease (irPD) or death up to 15 months after EoT | — |
Countries
Denmark
Contacts
Public ContactThomas Eskildsen
KLIFO A/S
Outcome results
None listed