Advanced Non Small Cell Lung CancerPhase 1/2NCT04032847
ATL001 in Patients With Advanced Unresectable or Metastatic NSCLC
A Phase 1/2 study testing ATL001 and Pembrolizumab in people with Advanced Non Small Cell Lung Cancer, run by Achilles Therapeutics UK Limited at 19 sites in 5 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Non Small Cell Lung Cancer
- What is being tested?
- ATL001 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 19 sitesin 5 countries
- Study dates
- 8 Jul 2019to 26 Sep 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must be at 18-75 years old.
- Patients must have confirmed diagnosis of non-small cell lung cancer that is considered to be smoking related.
- Patient is considered medically fit to undergo procurement of starting material and ATL001 administration procedures.
- ECOG Performance Status 0-1.
- Adequate organ function per the laboratory parameters defined in the protocol.
- Anticipated life expectancy ≥ 6 months at the time of tissue procurement.
- Measurable disease according to RECIST 1.1 criteria.
- Additional Inclusion Criteria will apply as per the protocol.
Who cannot join
- 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.
- Patients with hepatitis B or C, human immunodeficiency virus infection (HIV1/2), syphilis or HTLVI/II infection.
- 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.
- Patients requiring immunosuppressive treatments.
- Patients requiring regular steroids at dose higher than prednisolone 10mg/day (or equivalent)
- Patients with superior vena cava syndrome.
Show all 12Show fewer
- Patients with clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.
- 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.
- 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)
- Patients with a history of organ transplantation
- Patients who have previously received any investigational cell or gene therapies
- Additional Exclusion Criteria will apply as per the protocol.
Trial locations and contacts
19 sites in 5 countries.
19 sites in 5 countries
United Kingdom9 sites
University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
Birmingham, B15 2GW
Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
Cambridge
The Leeds Teaching Hospitals NHS Trust, St James's University Hospital
Leeds, LS9 7TF
University College London Hospitals (UCLH) NHS Foundation Trust, University College Hospital
London, NW1 2PG
Guys and St Thomas' NHS Foundation Trust, Guy's Hospital
London, SE19RT
The Christie NHS Foundation Trust, Christie Hospital
Manchester, M20 4BX
Manchester University NHS Foundation Trust, Wythenshawe Hospital
Manchester, M23 9LT
The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital
Newcastle upon Tyne
University Hospital Southampton NHS Foundation Trust, Southampton General Hospital
Southampton
Spain4 sites
Hospital Clinic de Barcelona
Barcelona, Catalonia, 08036
Instituto de Investigación Sanitaria Fundación Jimenez Díaz
Madrid, 28040
Centro Integral Oncologico Clara Campal Hospital Universitario HM Sanchinarro
Madrid, 28050
Hospital Clinico Universitario de Valencia
Valencia, 46010
United States3 sites
Yale University School of Medicine
New Haven, Connecticut, 06510
Memorial Sloan Kettering Cancer Center
New York, New York, 10017
Moffitt Cancer Center
Tampa, Florida, 33612
Germany2 sites
Universitätsklinikum Carl Gustav Carus Dresden
Dresden, 01307
Universitätsklinikum Essen
Essen, 45147
About this study
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
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).
Read the 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.
- Conditions
- Advanced Non Small Cell Lung Cancer
- Being tested
- ATL001, Pembrolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATL001Biological
ATL001 infusion
PembrolizumabDrug
Checkpoint inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a low dose regimen of IL- 2. Receives: Biological: ATL001 |
| Cohort B | Experimental | Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001 in combination with a checkpoint inhibitor, followed by a low dose regimen of IL- 2. Receives: Biological: ATL001; Drug: Pembrolizumab |
| Cohort C | Experimental | Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a higher dose regimen of IL-2. Receives: Biological: ATL001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Treatment Emergent Adverse Events (TEAEs) to Evaluate Safety and Tolerability
Evaluate TEAEs and serious AEs, by incidence, severity and relationship to ATL001
Measured: 62 months due to early termination
Secondary outcomes (7)
Disease Assessment for Change From Baseline in Tumour Size
Evaluate the clinical activity of ATL001 in patients with advanced NSCLC using change from baseline in tumour size at week 6 , week 12 and best overall change from baseline, as assessed by investigator and independent central review (ICR)
Measured: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Disease Assessment for Time to Response (TTR) From ATL001 Infusion
Evaluate the endpoint of TTR by the investigator and ICR, per RECIST v1.1 and im-RECIST
Measured: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Disease Assessment for Objective Response Rate (ORR)
Evaluate the endpoint of overall response rate (ORR), as assessed by investigator and ICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune modified RECIST( im-RECIST).
RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) is a standardized system for measuring tumor response to treatment in clinical trials. Tumors are assessed by imaging (e.g., CT or MRI) based on changes in size. Responses are categorized as:
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥30% reduction in the sum of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD).
Progressive Disease (PD): ≥20% increase in the sum of target lesions, or appearance of new lesions.
These criteria help assess the efficacy of treatments in solid tumors supported by im-RECIST in immunotherapy.
Measured: Every 6 weeks for 6 months, then every 3 months (up to 62 months due to early termination)
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
Evaluate the endpoint of DOR by the investigator and ICR, per RECIST v1.1 and im-RECIST
Measured: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Disease Assessment for Disease Control Rate (DCR)
Evaluate the endpoints of DCR as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST
Measured: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Disease Assessment for Progression-Free Survival (PFS)
Evaluate the efficacy endpoints of PFS as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST
Measured: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Overall Survival (OS)
Evaluate OS by the investigator
Measured: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2019
- Study start8 Jul 2019
- Primary completion26 Sep 2024
- Study completion26 Sep 2024
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Achilles Therapeutics UK Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, MD, Study director, Achilles Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04032847
- Sponsor's protocol ID
- ATX-NS-001
- Status last verified
- Feb 2025
- First submitted
- 17 Jul 2019
- Last updated
- 10 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04032847
- Acronym / sponsor ID
- ATX-NS-001
- Conditions
- Advanced Non Small Cell Lung Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Achilles Therapeutics UK LimitedIndustry (pharma, biotech, devices)
- Study start
- 8 Jul 2019 (actual)
- Primary completion
- 26 Sep 2024 (actual)
- Study completion
- 26 Sep 2024 (actual)
- First posted
- 25 Jul 2019 (actual)
- Results
- Posted 10 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Biological: ATL001Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a low dose regimen of IL- 2. |
| Cohort B | Experimental | Biological: ATL001, Drug: PembrolizumabFollowing lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001 in combination with a checkpoint inhibitor, followed by a low dose regimen of IL- 2. |
| Cohort C | Experimental | Biological: ATL001Following lymphodepletion with enhanced host conditioning, infusion of cell therapy product ATL001, followed by a higher dose regimen of IL-2. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patient must be at 18-75 years old.
- Patients must have confirmed diagnosis of non-small cell lung cancer that is considered to be smoking related.
- Patient is considered medically fit to undergo procurement of starting material and ATL001 administration procedures.
- ECOG Performance Status 0-1.
- Adequate organ function per the laboratory parameters defined in the protocol.
Key exclusion criteria (12 listed)
- 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.
- Patients with hepatitis B or C, human immunodeficiency virus infection (HIV1/2), syphilis or HTLVI/II infection.
- 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.
- Patients requiring immunosuppressive treatments.
- Patients requiring regular steroids at dose higher than prednisolone 10mg/day (or equivalent)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ATL001ATL001 infusion | Biological | Cohort A, Cohort B, Cohort C |
| PembrolizumabCheckpoint inhibitor | Drug | Cohort B |
Primary outcome
Assessment of Treatment Emergent Adverse Events (TEAEs) to Evaluate Safety and Tolerability
Time frame: 62 months due to early termination
Evaluate TEAEs and serious AEs, by incidence, severity and relationship to ATL001
7 secondary outcomes
Disease Assessment for Change From Baseline in Tumour Size
Time frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Disease Assessment for Time to Response (TTR) From ATL001 Infusion
Time frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Disease Assessment for Objective Response Rate (ORR)
Time frame: Every 6 weeks for 6 months, then every 3 months (up to 62 months due to early termination)
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
Time frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Disease Assessment for Disease Control Rate (DCR)
Time frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Disease Assessment for Progression-Free Survival (PFS)
Time frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Overall Survival (OS)
Time frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor, MD study director
Achilles Therapeutics
19 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ATL001 and Pembrolizumab in people with Advanced Non Small Cell Lung Cancer, run by Achilles Therapeutics UK Limited at 19 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United Kingdom, Spain, United States, Germany, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of Treatment Emergent Adverse Events (TEAEs) to Evaluate Safety and Tolerability (time frame: 62 months due to early termination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2025.