Advanced Non-Small Cell Lung Cancer avenocellular carcinoma
Conditions
Interventions
Eligible patients will receive a single intravenous infusion of ATL001,
following pre-conditioning treatment. The infusion should be administered as
soon as possible after thawing and within 30 minu
Sponsors
Achilles therapeutics UK Limited
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: To be eligible to participate in this study, eligibility criteria will apply at two timepoints: at study entry prior to procurement of tumour and blood for manufacture of ATL001, and then prior to lymphodepletion for treatment with ATL001. Inclusion Criteria: 1. Patient must be at least 18 years old at the screening visit. 2. Patient must have given written informed consent to participate in the study. 3. Patients must have histologically confirmed diagnosis of non-small cell lung cancer that 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. Eastern Cooperative Oncology Group (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*/L. c. Absolute Neutrophil Count (ANC) >= 1.5 x10*/L. d. Platelets >= 100 x10*/L. e. PT and APTT = 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. Non-sterilised 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 F for pregnancy testing requirements in Germany. See Section 4.3 for details of acceptable methods of contraception. In addition to 1-8, the following inclusion criteria must be met prior to tissue procurement: 9. To be eligible to enter this study for procurement, the 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 (These patients will not receive ATL001 until their disease has progressed following standard of care therapies, or if they cannot tolerate standard of care therapies - see inclusion number 11). b. Patients with advanced stage (III-IV) NSCLC who have received or are receiving standard treatments and have accessible sites of residual 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 1-8, the following inclusion criteria must be met prior to lymphodepletion for treatment with ATL001: 11. Patients must
Exclusion criteria
Exclusion criteria: Exclusion Criteria: 1. Patients with known CNS metastases at the time of screening. 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 = 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) 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 Prostate-Specific Antigen (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. refractory disease). 19. Patients with a known 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) for reference safety information for pembrolizumab). All exclusion criteria except 2, 3, 4, 17 and 18 will apply again to all patients 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Endpoint: Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) following tissue procurement and administration of lymphodepletion agents, ATL001 and IL-2. | — |
Secondary
| Measure | Time frame |
|---|---|
| Endpoints; * Percentage change from baseline in tumour size at 6 weeks, 12 weeks and best change from baseline. * Overall Response Rate (ORR) (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 (PFS) (based on RECIST v1.1 and imRECIST). * Overall survival (OS). Exploratory: 1. To evaluate thepersistence, phenotype and functionality of cNeT and to explore possible relationships with clinical outcomes Measures of numbers, phenotype and functionality of immune cells in starting materials, product intermediates and ATL001 product. Measures of the persistence, phenotype and functionality of infused T cells in the peripheral blood. 2. To evaluate potential biomarkers of clinical activity and factors affecting response Changes from baseline in bespoke clonal and subclonal mutation/neoantigen specific circulating tumour DNA (ctDNA) panels. Potential factors affecting response to be explored include but are not limited to: patient factors e.g. previous therapies; tumour biology factors e.g. total tumour mutation burden at baseline, tumour T cell infiltrate, major histocompatibility complex (MHC) expression and loss of heterozygosity (LOH-HLA), tumour expression of PD-L1 and other immune checkpoint proteins, Lung Immune Prognostic Score and primary vs acquired resistance to a PD-1/PD-L1 inhibitor; product factors e.g. cNeT dose; cNeT engraftment. 3. To evaluate the manufacturing rate and factors that may affect the quality of ATL001 Number of products made from procured samples. Reasons for not manufacturing products. Potential factors affecting ATL001 quality include but are not limited to: patient factors e.g. previous therapies; procurement sample quality; tumour biology factors e.g. PD-L1 expression and TIL phenotype. 4. To evaluate the util | — |
Countries
Netherlands
Outcome results
None listed