Clinical trial NCT04032847: ATL001 in Patients With Advanced Unresectable or Metastatic NSCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Non Small Cell Lung Cancer
Lead sponsor: Achilles Therapeutics UK Limited
Sponsor class: INDUSTRY
First posted: 2019-07-25
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a first-in-human, open-label, multi-centre, phase I/IIa study to characterise the safety and clinical activity autologous clonal neoantigen reactive T cells (cNeT) administered intravenously in adults with advanced non-small cell lung cancer (NSCLC).

Detailed description: This is a first-in-human, open-label, multi-centre, phase I/IIa study to characterise the safety and clinical activity of autologous clonal neoantigen reactive T cells (cNeT) administered intravenously in adults with advanced non-small cell lung cancer (NSCLC).

Patients will initially enter the study for procurement of tumour materials required to manufacture ATL001.

Following manufacture of ATL001, the product will be given back to eligible patients following lymphodepletion. Patients will continue to be followed up for a minimum of 5 years, as part of a separate Long Term Follow Up Protocol, or, if the separate protocol is not available at the study site, within this protocol.

Eligibility criteria: Inclusion Criteria:

1. Patient must be at 18-75 years old.
2. Patients must have confirmed diagnosis of non-small cell lung cancer that is considered to be smoking related.
3. Patient is considered medically fit to undergo procurement of starting material and ATL001 administration procedures.
4. ECOG Performance Status 0-1.
5. Adequate organ function per the laboratory parameters defined in the protocol.
6. Anticipated life expectancy ≥ 6 months at the time of tissue procurement.
7. Measurable disease according to RECIST 1.1 criteria.

Additional Inclusion Criteria will apply as per the protocol.

Exclusion Criteria:

1. Patients with untreated, symptomatic or progressing CNS metastases. Lesions should be clinically and radiologically stable for 2 months after treatment and should not require steroids.
2. Patients with hepatitis B or C, human immunodeficiency virus infection (HIV1/2), syphilis or HTLVI/II infection.
3. 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.
4. Patients requiring immunosuppressive treatments.
5. Patients requiring regular steroids at dose higher than prednisolone 10mg/day (or equivalent)
6. Patients with superior vena cava syndrome.
7. Patients with clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.
8. Patients with a history of immune mediated central nervous system toxicity, or a history of ≥ Grade 2 diarrhoea/colitis within the past 6 months caused by previous immunotherapy.
9. 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)
10. Patients with a history of organ transplantation
11. Patients who have previously received any investigational cell or gene therapies

Additional Exclusion Criteria will apply as per the protocol.

Primary outcomes:
measure: Assessment of Treatment Emergent Adverse Events (TEAEs) to Evaluate Safety and Tolerability
timeFrame: 62 months due to early termination
Secondary outcomes:
measure: Disease Assessment for Change From Baseline in Tumour Size
timeFrame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
measure: Disease Assessment for Time to Response (TTR) From ATL001 Infusion
timeFrame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
measure: Disease Assessment for Objective Response Rate (ORR)
timeFrame: Every 6 weeks for 6 months, then every 3 months (up to 62 months due to early termination)
measure: Disease Assessment for Duration of Response (DoR). The DoR is Defined as the Time From the Date of First Documented Response Until the Date of Documented Disease Progression or Death
timeFrame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
measure: Disease Assessment for Disease Control Rate (DCR)
timeFrame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
measure: Disease Assessment for Progression-Free Survival (PFS)
timeFrame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
measure: Overall Survival (OS)
timeFrame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
state: Catalonia
city: Madrid
country: Spain
facility: Instituto de Investigación Sanitaria Fundación Jimenez Díaz
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal Hospital Universitario HM Sanchinarro
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals NHS Trust, St James's University Hospital
city: London
country: United Kingdom
facility: University College London Hospitals (UCLH) NHS Foundation Trust, University College Hospital
city: London
country: United Kingdom
facility: Guys and St Thomas' NHS Foundation Trust, Guy's Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust, Christie Hospital
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust, Wythenshawe Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust, Southampton General Hospital
Study officials:
affiliation: Achilles Therapeutics
name: Medical Monitor, MD
role: STUDY_DIRECTOR
References: