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    Summary
    EudraCT Number:2018-001005-85
    Sponsor's Protocol Code Number:ATX-NS-001
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2020-09-14
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - PEI
    A.2EudraCT number2018-001005-85
    A.3Full title of the trial
    An open label, multi-centre, phase I/IIa study evaluating the safety and clinical activity of neoantigen reactive T cells in patients with advanced non-small cell lung cancer.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A first-in-human clinical trial in adult patients with advanced non-small cell lung cancer of a personalised therapy targeting specific mutations that occur in all cancer cells within a single patient.
    A.3.2Name or abbreviated title of the trial where available
    ATX-NS-001 - ATL001 for the Treatment of Non-Small Cell Lung Cancer
    A.4.1Sponsor's protocol code numberATX-NS-001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04032847
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAchilles Therapeutics UK Limited
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAchilles Therapeutics UK Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAchilles Therapeutics UK Limited
    B.5.2Functional name of contact pointRegulatory Affairs
    B.5.3 Address:
    B.5.3.1Street Address245 Hammersmith Road
    B.5.3.2Town/ cityLondon
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+442045519198
    B.5.5Fax number+442081815141
    B.5.6E-mailregulatory@achillestx.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameATL001
    D.3.2Product code ATL001
    D.3.4Pharmaceutical form Dispersion for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNot yet available
    D.3.9.3Other descriptive nameATL001
    D.3.9.4EV Substance CodeSUB282178
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number50000000 to 10000000000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product Yes
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Keytruda
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPembrolizumab
    D.3.9.3Other descriptive namePembrolizumab
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number400
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Non-small cell lung cancer
    E.1.1.1Medical condition in easily understood language
    Lung cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10001245
    E.1.2Term Adenosquamous cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10001247
    E.1.2Term Adenosquamous cell lung cancer recurrent
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10001251
    E.1.2Term Adenosquamous cell lung cancer stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10001254
    E.1.2Term Adenosquamous cell lung cancer stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10023775
    E.1.2Term Large cell lung cancer recurrent
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10023779
    E.1.2Term Large cell lung cancer stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10023780
    E.1.2Term Large cell lung cancer stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10029515
    E.1.2Term Non-small cell lung cancer recurrent
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10029519
    E.1.2Term Non-small cell lung cancer stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10029520
    E.1.2Term Non-small cell lung cancer stage IIIA
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10029521
    E.1.2Term Non-small cell lung cancer stage IIIB
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10029522
    E.1.2Term Non-small cell lung cancer stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 27.0
    E.1.2Level PT
    E.1.2Classification code 10050017
    E.1.2Term Lung cancer metastatic
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 27.0
    E.1.2Level PT
    E.1.2Classification code 10059515
    E.1.2Term Non-small cell lung cancer metastatic
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10025044
    E.1.2Term Lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10001246
    E.1.2Term Adenosquamous cell lung cancer NOS
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10029514
    E.1.2Term Non-small cell lung cancer NOS
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10001253
    E.1.2Term Adenosquamous cell lung cancer stage IIIB
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10023774
    E.1.2Term Large cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10001252
    E.1.2Term Adenosquamous cell lung cancer stage IIIA
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10025048
    E.1.2Term Lung cancer non-small cell recurrent
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10025052
    E.1.2Term Lung cancer non-small cell stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10025054
    E.1.2Term Lung cancer non-small cell stage IIIB
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10025053
    E.1.2Term Lung cancer non-small cell stage IIIA
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10025055
    E.1.2Term Lung cancer non-small cell stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 27.0
    E.1.2Level LLT
    E.1.2Classification code 10066490
    E.1.2Term Progression of non-small cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 27.0
    E.1.2Level PT
    E.1.2Classification code 10069730
    E.1.2Term Large cell lung cancer metastatic
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the safety and tolerability of the investigational product after administration to patients.
    E.2.2Secondary objectives of the trial
    To evaluate if patients have a clinically meaningful response to the investigational product.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion criteria will apply at multiple timepoints.

    Inclusion Criteria:
    1. Patient must be between 18 and 75 years old at the screening visit.
    2. Patient must have given written informed consent to participate in the study.
    3. Patient must have histologically confirmed diagnosis of non-small cell lung cancer, which is considered to be smoking-related.
    4. Patient is considered medically fit enough to undergo all study procedures and interventions: procedures to procure blood and tumour tissue, including a general anaesthetic if required, and to receive fludarabine, cyclophosphamide and IL-2 at protocol doses and schedules.
    5. Patient is considered, in the opinion of the Investigator, capable of adhering to the protocol.
    6. ECOG Performance Status 0-1.
    7. Adequate organ function, indicated by the following laboratory parameters:
    a. Haemoglobin ≥ 10.0 g/dL.
    b. White Blood Cell Count (WBC) ≥ 3.0 x10^9/L.
    c. Absolute Neutrophil Count (ANC) ≥ 1.5 x10^9/L (without support of filgrastim (G-CSF)).
    d. Platelets ≥ 100 x10^9/L.
    e. INR/PT and APTR/APTT < 1.5x UL, unless receiving therapeutic anticoagulation. Investigator discretion is required to ensure surgery is safe or that anticoagulants can be safely stopped.
    f. AST or ALT ≤ 2.5x ULN.
    g. Bilirubin < 1.5x ULN (or < 3 x ULN in Gilbert’s Syndrome).
    h. Creatinine clearance/estimated GFR ≥ 50 mL/min.
    8. Female patients who are of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 12 months after the ATL001 infusion. Nonsterilised male participants who intend to be sexually active with a female partner of childbearing potential must use an acceptable method of contraception from the time of screening, throughout the duration of the study and for at least 6 months after the ATL001 infusion. Refer to Appendix G for pregnancy testing requirements in Germany. See Section 4.3 for details of acceptable methods of contraception.
    In addition to a re-evaluation of criteria 1-8, the following inclusion criteria must also be met prior to tissue procurement:
    9. To be eligible to enter this study for procurement, a patient must fall into one of the following
    groups:
    a. Patients with advanced stage (III-IV) NSCLC who have accessible sites of disease suitable for collection of adequate tissue for ATL001 manufacture prior to starting standard treatment.
    b. Patients with advanced stage (III-IV) NSCLC who have received or are receiving standard treatments and have accessible sites of disease suitable for collection of adequate tissue for ATL001 manufacture.
    c. Other patients with advanced stage disease for whom no other alternative approved treatments are available, may be considered on a case-by-case basis and should be discussed with the Sponsor prior to enrolment.
    10. Anticipated life expectancy ≥ 6 months at the time of tissue procurement.
    In addition to a re-evaluation of criteria 1-8, the following inclusion criteria must also be met prior to lymphodepletion for treatment with ATL001:
    11. Patients must have locally advanced unresectable or metastatic NSCLC and:
    a. Whose disease has progressed or recurred following standard of care. This includes patients who have received a component of standard of care therapy as part of a previous clinical trial in first line treatment; or
    b. Who are ineligible for, or who cannot tolerate, standard of care therapies. Patients who stop treatment due to immunotherapy toxicities do not need to progress in order to receive treatment with ATL001.
    12. Patients must have measurable disease according to RECIST v1.1 criteria prior to lymphodepletion.
    13. Patient is considered, in the opinion of the Investigator, well enough (i.e. ECOG Performance Status 0-1) to receive ATL001 treatment (This will be checked prior to lymphodepletion and again prior to receiving ATL001).
    In addition to 1-13, except inclusion 11a, the following inclusion criteria must be met for patients to be eligible for treatment in Cohort B:
    14. Prior to treatment with ATL001, the treatment regimen must have included a PD- 1/PD-L1 inhibitor and patients should have experienced:
    a. Radiological disease progression; or
    b. Stable disease following at least 4 doses of a PD-1/PD-L1 inhibitor.
    15. In addition to the need for highly effective contraception as outlined in Inclusion Criterion 8 above, female patients in Cohort B of childbearing potential must agree to use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. Patients must also agree to provide a serum or urine pregnancy test before each pembrolizumab administration during the treatment period in Cohort B.
    E.4Principal exclusion criteria
    Exclusion criteria will apply at multiple timepoints.

    Exclusion Criteria:
    1. Patients with known central nervous system (CNS) metastases that are untreated or symptomatic or progressing. Lesions should be clinically and radiologically stable for 2 months after treatment, as determined by MRI or CT evaluation, in line with accepted standard of care procedures, and should not require steroids.
    2. Patients with hepatitis B or C, human immunodeficiency virus infection (HIV1/2), syphilis or HTLVI/II infection (see Section 6.1.1).
    3. Patients who have never smoked (defined as having smoked < 100 cigarettes in their lifetime, per WHO criteria).
    4. Patients for whom there is documented evidence of an actionable tumour driver oncogene mutation (EGFR, ALK or ROS-1) at the time of initial screening. Patients who have progressed on standard targeted therapies, or for whom no approved targeted treatments are available, are not excluded.
    5. Patients with active, known, or suspected autoimmune disease requiring immunosuppressive treatments.
    6. Patients requiring regular treatment with steroids at a dose higher than prednisolone 10 mg/day (or equivalent).
    7. Patients with superior vena cava syndrome.
    8. Patients with a current or recent history, as determined by the Investigator, of clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease. Additionally, the following criteria apply:
    a. Patients with a Left Ventricular Ejection Fraction (LVEF) < 45%.
    b. Patients with a history of coronary revascularization.
    c. Patients with clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, 2° or 3° heart block.
    d. Patients with a forced expiratory volume in one second (FEV1) of less than or equal to 60% of their predicted normal.
    9. Patients with a history of immune mediated central nervous system toxicity that was caused by, or suspected to be caused by, immunotherapy.
    10. Patients with a history of ≥ Grade 2 diarrhoea/colitis caused by previous immunotherapy within 6 months of screening. Patients that have been asymptomatic for at least 6 months or have had a normal colonoscopy post-immunotherapy (with uninflamed mucosa by visual assessment following discontinuation of immune suppression other than permitted modified release steroids) are not excluded.
    11. Patients who are pregnant or breastfeeding.
    12. Patients who have undergone major surgery in the previous 3 weeks.
    13. Patients with an active concurrent cancer or a history of cancer within the past 3 years (except for in situ carcinomas, early prostate cancer with normal PSA or non-melanomatous skin cancers).
    14. Patients with a history of organ transplantation.
    15. Patients who have previously received any investigational cell or gene therapies.
    16. Patients with contraindications for cyclophosphamide, fludarabine and IL-2 at per protocol doses (see Investigator’s Brochure for details).
    17. Patients who have received any cytotoxic chemotherapy or anti-angiogenesis agent within the 3 weeks prior to tissue and blood procurement.
    18. Patients with evidence of disease progression at the first scan after commencing standard first line therapy (i.e. primary refractory disease), unless responsive to subsequent lines of therapy. Patients who are refractory to pembrolizumab monotherapy are not excluded.
    19. Patients with a confirmed history of allergic reactions to amphotericin b, penicillin and/or streptomycin.
    In addition, the following exclusion criteria will apply for eligibility for Cohort B:
    20. Patients with any contraindications for pembrolizumab (Refer to the latest available prescribing information (e.g. SmPC/Package Insert) for reference safety information for pembrolizumab).
    All exclusion criteria, except 2, 3, 4 and 17, will apply again prior to lymphodepletion for treatment with ATL001.
    In addition, the following criteria will apply:
    21. Patients who have received a live vaccination within the 28 days prior to lymphodepletion.
    22. Patients with an active infection requiring antibiotics.
    23. Patients who have received any cytotoxic chemotherapy within the 3 weeks prior to lymphodepletion.
    E.5 End points
    E.5.1Primary end point(s)
    To assess the safety and tolerability of ATL001 as a monotherapy and in combination with pembrolizumab:
    Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) following tissue procurement and administration of lymphodepletion agents, ATL001 (monotherapy or in combination with pembrolizumab) and IL-2.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The following interim analyses of efficacy may be performed:
    1. Optional interim analyses when approximately 10 evaluable patients have been followed up for 6 and 12 weeks.
    2. An interim analysis of each treatment cohort separately when all patients in a treatment cohort separately have been followed up for 12 weeks.
    3. A final analysis when all patients have either died or have been followed up for 2 years.
    Additional interim analyses may be performed at other times during the study.
    E.5.2Secondary end point(s)
    To evaluate the clinical efficacy of ATL001 treatment as a monotherapy and in combination with pembrolizumab:
    • Percentage change from baseline in tumour size at 6 weeks, 12 weeks and best change from baseline.
    • Overall Response Rate (based on RECIST v1.1 and imRECIST).
    • Time to response (based on RECIST v1.1 and imRECIST).
    • Duration of response (based on RECIST v1.1 and imRECIST).
    • Disease Control Rate (CR + PR + durable SD) (based on RECIST v1.1).
    • Progression free survival (based on RECIST v1.1 and imRECIST).
    • Overall survival.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The following interim analyses of efficacy may be performed:
    1. Optional interim analyses when approximately 10 evaluable patients have been followed up for 6 and 12 weeks.
    2. An interim analysis of each treatment cohort separately when all patients in a treatment cohort separately have been followed up for 12 weeks.
    3. A final analysis when all patients have either died or have been followed up for 2 years.
    Additional interim analyses may be performed at other times during the study.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA8
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United Kingdom
    United States
    France
    Germany
    Spain
    E.8.7Trial has a data monitoring committee Yes
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months10
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 38
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 12
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 24
    F.4.2.2In the whole clinical trial 50
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    The investigational medicinal product is administered as a single infusion of autologous cells. It is anticipated that most patients will receive a single administration of cells. Re-administration may be possible if the patient is fit enough to undergo a second tumour biopsy for the manufacture of a second dose or re-conditioning with fludarabine and cyclophosphamide if needed in the case a second dose was able to be manufactured from the initial tumour biopsy upon initial entry to the study.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-03-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-06
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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