An Open-Label, Multi-Center Phase I/IIa Study Evaluating the Safety and Clinical Activity of Neoantigen Reactive T cells in Patients with Advanced Non-Small Cell Lung Cancer (CHIRON)
This is a first-in-human, open-label, phase I/IIa study to characterise the safety and clinical activity autologous clonal neoantigen T cells (cNeT) administered intravenously in adults with advanced non-small cell lung cancer (NSCLC).
Primary Objective: -To assess the safety and tolerability of ATL001 therapy. Secondary Objective: -To evaluate the clinical efficacy of ATL001 using RECIST v1.1 and imRECIST. Exploratory Objectives: -To evaluate the persistence, phenotype and functionality of NAR-T cells and to explore possible relationships with clinical outcomes. -To evaluate potential biomarkers of clinical activity and factors affecting response. -To evaluate manufacturing rate and factors that may affect the quality of ATL001. -To evaluate the utility of a bespoke plasma ctDNA assay. -To evaluate pleural fluid as a source of T cells and free tumor DNA.
Cell Therapy; Chemotherapy (NOS); Immunotherapy; Therapy (NOS)
ATL001 (); IL-2 (Interleukin-2); Pembrolizumab (Keytruda); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)
- Patient must be at least 18 years old
- Patient must have given written informed consent
- Confirmed diagnosis of non-small cell lung cancer that is considered to be smoking related
- ECOG Performance status 0-1
- Anticipated life expectancy > 6 months
- Measurable disease according to RECIST 1.1 criteria
- Adequate organ function
- Patient is considered medically fit to undergo procurement of starting material and ATL001 administration procedures
- Patient is considered, in the opinion of the investigator, capable of adhering to the protocol.
- If female, patient must be either postmenopausal, sterilised or, if sexually active, effectively practicing a highly effective method of contraception.
- Male patients agree to ensure that they or their female partner(s) use a highly effective method of contraception during the study
- Patients with known central nervous system 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.
- Patients with active infectious disease
- Patients who are non-smokers
- Patients requiring immunosuppressive treatments.
- Patients requiring regular treatment with systemic steroids
- Patients with superior vena cava syndrome
- Patients with clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease
- Patients who are pregnant or breastfeeding
- Patients who have undergone major surgery in the previous 3 weeks
- Patients with an active concurrent cancer or a history of cancer within the past 3 years (except for in situ carcinomas or non-melanomatous skin cancers)
- Patients with a history of organ transplantation.
- Patients who have received any investigational cell or gene therapies
- Patients with contraindications for protocol specified agents
- Patients with a history of immune mediated central nervous system toxicity with causal or suspected causal link to immunotherapy
- Patients with a history of Grade 2 or greater diarrhea/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.
- Patients wuth confirmed history of allergic reactions to amphotericin b, penicillin and/or streptomycin
- Additional exclusion criteria may apply to define procedures within the protocol
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