E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Soft tissue sarcoma is a rare type of cancer that begins in the tissues that connect, support and surround other body structures. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10072990 |
E.1.2 | Term | Soft tissue neoplasms malignant and unspecified |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
* 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 |
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E.2.2 | Secondary objectives of the trial |
* 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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | 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) |
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E.5.1.1 | 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) |
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E.5.2 | 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 |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |