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TerminatedNCT03997474Updated Mar 7, 2025Results posted

ATL001 in Patients With Metastatic or Recurrent Melanoma

A Phase 1/2 interventional study of ATL001 and Checkpoint Inhibitor in Melanoma, sponsored by Achilles Therapeutics UK Limited. Terminated at 10 sites in 2 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-03-07.

Sponsored by Achilles Therapeutics UK Limited · Phase 1/2, Interventional, and Treatment

Why this study was terminated
Sponsor decision
Phase
Phase 1/2
Study type
Interventional
Enrollment
13
Allocation
Non-randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

This is a first-in-human, open-label, multi-centre, phase I/IIa study to characterize the safety and clinical activity of ATL001, autologous clonal neoantigen reactive T cells (cNeT) administered intravenously in adults with metastatic or recurrent melanoma.

Read the detailed description

This is a first-in-human, open-label, multi-centre, phase I/IIa study to characterize the safety and clinical activity autologous clonal neoantigen reactive T cells (cNeT) administered intravenously in adults with metastatic or recurrent melanoma.

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 be followed up for a period of 24 months post ATL001 infusion in the study.

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.

02

Conditions studied

  • Melanoma

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03

In context

Melanoma

3,006 studies on the registry are indexed under Melanoma; 520 are open to participants now.

This study's enrollment of 13 is below the median of 38 across 2,351 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

Achilles Therapeutics UK Limited is the lead sponsor of 3 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Patient must be at least 18 years old.
  2. Patient must have given written informed consent.
  3. Patients must have histologically confirmed diagnosis of melanoma.
  4. Patient is considered medically fit to undergo procurement of starting material and ATL001 administration procedures.
  5. ECOG Performance Status 0-1.
  6. Adequate organ function per the laboratory parameters defined in the protocol.
  7. Female patients who are of childbearing potential must agree to use a highly effective method of contraception during the study 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.
  8. Anticipated life expectancy ≥ 6 months at the time of tissue procurement.
  9. Measurable disease according to RECIST v1.1 criteria. Additional inclusion criteria will apply as per the study protocol.

Exclusion criteria

Exclusion Criteria:

  1. Patients with known leptomeningeal disease or untreated, symptomatic or progressing central nervous system (CNS) metastases. Lesions should be clinically and radiologically stable for 2 months after treatment and should not require steroids.
  2. Patients with ocular, acral or mucosal melanoma.
  3. Patients with hepatitis B or C, human immunodeficiency virus infection (HIV 1/2), syphilis or HTLV I/II infection.
  4. Patients requiring immunosuppressive treatments.
  5. Patients requiring regular steroids at a dose higher than prednisolone 10mg/day (or equivalent).
  6. Patients with clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological, or neurological disease.
  7. Patients with a history of immune mediated (CNS) toxicity or ≥ Grade 2 diarrhoea/colitis caused by, , previous immunotherapy within the past 6 months.
  8. Patients who are pregnant or breastfeeding.
  9. Patients who have undergone major surgery in the previous 3 weeks.
  10. 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).
  11. Patients with a history of organ transplantation.
  12. Patients who have previously received any investigational cell or gene therapies.
  13. Patients with contraindications for protocol specified agents.

Additional Exclusion criteria will apply as per the study protocol.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
13 participants (actual)

Study arms

  • Experimental
    Cohort A

    Following lymphodepletion, infusion of cell therapy product ATL001, followed by a low dose regimen of IL- 2.

    Biological: ATL001

  • Experimental
    Cohort B

    Following lymphodepletion, infusion of cell therapy product ATL001 in combination with a checkpoint inhibitor, followed by a low dose regimen of IL-2.

    Biological: ATL001 · Drug: Checkpoint Inhibitor

  • Experimental
    Cohort C

    Following lymphodepletion, infusion of cell therapy product ATL001, followed by a higher dose regimen of IL-2.

    Biological: ATL001

Interventions

  • BiologicalATL001

    ATL001 infusion

  • DrugCheckpoint Inhibitor

    Nivolumab

06

What researchers measure

Primary outcomes

  1. Assessment of Treatment Emergent Adverse Events to Evaluate Safety and Tolerability: CTCAE

    Evaluate treatment-emergent adverse events (TEAEs) and serious AEs, per CTCAE, by incidence, severity and relationship to ATL001

    Time frame: 60 months due to early termination

Secondary outcomes

  1. Disease Assessment for Change From Baseline in Tumour Size

    Evaluate the clinical activity of ATL001 in patients with recurrent or metastatic melanoma 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).

    Time frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

  2. Disease Assessment for Overall Response Rate

    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.

    Time frame: Every 6 weeks for 6 months, then every 3 months (up to 60 months due to early study termination)

  3. Disease Assessment for Time to Response and Duration of Response

    Evaluate the endpoints of time to response and duration of response (DOR) by the investigator and ICR, per RECIST v1.1 and im-RECIST.

    Time frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

  4. Disease Assessment for Disease Control Rate

    Evaluate the endpoints of disease control rate (DCR) as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST.

    Time frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

  5. Disease Assessment for Progression-Free Survival

    Evaluate the efficacy endpoints of progression-free survival (PFS) as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST.

    Time frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

  6. Overall Survival

    Evaluate overall survival (OS) by investigator

    Time frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

07

Results

Posted Mar 7, 2025

Participant flow

Participant flow — Overall Study
MilestoneCohort ACohort BCohort C
Started922
Completed000
Not completed922
Withdrew: Death621
Withdrew: Physician decision200
Withdrew: Study terminated by sponsor101

Outcome measures

PrimaryAssessment of Treatment Emergent Adverse Events to Evaluate Safety and Tolerability: CTCAE

Evaluate treatment-emergent adverse events (TEAEs) and serious AEs, per CTCAE, by incidence, severity and relationship to ATL001

Time frame:
60 months due to early termination
Reported as:
Count of participants · Participants
Assessment of Treatment Emergent Adverse Events to Evaluate Safety and Tolerability: CTCAE
ParticipantsCohort ACohort BCohort C
TEAEs922
TEAEs related to any component of study treatment822
Lymphodepletion related TEAEs812
ATL001 related TEAEs IL-2 related TEAEs Serious TEAEs522
IL-2 related TEAEs722
Nivolumab related TEAEs000
Serious TEAEs310
Serious TEAEs related to any component of study treatment110
Serious Lymphodepletion related TEAEs000
Serious ATL001 related TEAEs110
Serious IL-2 related TEAEs110
Serious Nivolumab related TEAEs000
TEAEs with CTCAE grade >= 3621
TEAEs with CTCAE grade >= 3 related to any component of study treatment521
Lymphodepletion related TEAEs with CTCAE grade >= 3411
ATL001 related TEAEs with CTCAE grade >= 3210
IL-2 related TEAEs with CTCAE grade >= 3220
Nivolumab related TEAEs with CTCAE grade >= 3010
TEAEs leading to death010
TEAEs leading to death related to any component of study treatment000
SAEs321
SecondaryDisease Assessment for Change From Baseline in Tumour Size

Evaluate the clinical activity of ATL001 in patients with recurrent or metastatic melanoma 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).

Time frame:
Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

Results for this outcome have not been posted.

SecondaryDisease Assessment for Overall Response Rate

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.

Time frame:
Every 6 weeks for 6 months, then every 3 months (up to 60 months due to early study termination)
Reported as:
Count of participants · Participants
Disease Assessment for Overall Response Rate
ParticipantsCohort ACohort BCohort C
Responders000
Non-Responders922
SecondaryDisease Assessment for Time to Response and Duration of Response

Evaluate the endpoints of time to response and duration of response (DOR) by the investigator and ICR, per RECIST v1.1 and im-RECIST.

Time frame:
Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

Results for this outcome have not been posted.

SecondaryDisease Assessment for Disease Control Rate

Evaluate the endpoints of disease control rate (DCR) as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST.

Time frame:
Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

Results for this outcome have not been posted.

SecondaryDisease Assessment for Progression-Free Survival

Evaluate the efficacy endpoints of progression-free survival (PFS) as assessed by the investigator and ICR per RECIST v1.1 and im-RECIST.

Time frame:
Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

Results for this outcome have not been posted.

SecondaryOverall Survival

Evaluate overall survival (OS) by investigator

Time frame:
Every 6 weeks for 6 months, then every 3 months for a maximum of 84 months

Results for this outcome have not been posted.

Adverse events

Collected over Each patient that received ATL001 would have been followed up for 24 months, to withdrawal of consent or death. Patients would then continue to be followed up for a minimum of 5 years as part of long term follow up. The study was terminated early due to sponsor decision. The Median follow-up period was 12 weeks (range: 3 - 48 weeks).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort A8/9 (88.9%)3/9 (33.3%)9/9 (100%)
Cohort B2/2 (100%)2/2 (100%)2/2 (100%)
Cohort C1/2 (50%)1/2 (50%)2/2 (100%)
Most frequent serious events
Showing 10 of 11
Most frequent serious events
EventCohort ACohort BCohort C
Procedural painInjury, poisoning and procedural complications0/90/21/2
Immune effector cell-associated neurotoxicity syndromeNervous system disorders1/91/20/2
Adrenal insufficiencyEndocrine disorders0/91/20/2
Pneumonia aspirationInfections and infestations0/91/20/2
SepsisInfections and infestations2/90/20/2
Abdominal wall infectionInfections and infestations1/90/20/2
Klebsiella sepsisInfections and infestations1/90/20/2
ConstipationGastrointestinal disorders1/90/20/2
Drain site complicationInjury, poisoning and procedural complications1/90/20/2
HaematuriaRenal and urinary disorders1/90/20/2
Most frequent other events
Showing 10 of 123
Most frequent other events
EventCohort ACohort BCohort C
FatigueGeneral disorders3/91/22/2
AnaemiaBlood and lymphatic system disorders4/92/22/2
ConstipationGastrointestinal disorders3/92/21/2
NauseaGastrointestinal disorders6/92/21/2
Lymphocyte count decreasedInvestigations3/92/20/2
FallInjury, poisoning and procedural complications0/92/20/2
DyspnoeaRespiratory, thoracic and mediastinal disorders1/92/20/2
NeutropeniaBlood and lymphatic system disorders7/90/21/2
PyrexiaGeneral disorders6/91/21/2
DiarrhoeaGastrointestinal disorders5/91/20/2

Baseline characteristics

No differences.

Age, Categorical
Age, Categorical(Participants)Cohort ACohort BCohort CTotal
<=18 years0000
Between 18 and 65 years82212
>=65 years1001
Age, Continuous
Age, Continuous(years)Cohort ACohort BCohort CTotal
Mean50.4 ± 10.4959.5 ± 4.9536.5 ± 4.9549.7 ± 11.09
Sex: Female, Male
Sex: Female, Male(Participants)Cohort ACohort BCohort CTotal
Female2024
Male7209
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cohort ACohort BCohort CTotal
Hispanic or Latino0000
Not Hispanic or Latino92213
Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort ACohort BCohort CTotal
American Indian or Alaska Native0000
Asian0000
Native Hawaiian or Other Pacific Islander0000
Black or African American0000
White92213
More than one race0000
Unknown or Not Reported0000
Region of Enrollment
Region of Enrollment(participants)Cohort ACohort BCohort CTotal
United Kingdom92112
Spain0011
Body mass index (kg/m^2)
Body mass index (kg/m^2)(kg/m^2)Cohort ACohort BCohort CTotal
Mean28.52 ± 4.92225.55 ± 2.05222.90 ± 1.83827.2 ± 4.651
Baseline ECOG performance status
Baseline ECOG performance status(Participants)Cohort ACohort BCohort CTotal
Grade 02114
Grade 17119
08

Study locations

10 sites
  • Instituto de Investigación Sanitaria Fundación Jimenez Díaz
    Madrid, 28040, Spain
  • Centro Integral Oncologico Clara Campal (CIOCC) Hospital Universitario HM Sanchinarro
    Madrid, 28050, Spain
  • Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
    Cambridge, CB2 0QQ, United Kingdom
  • University College London Hospitals (UCLH) NHS Foundation Trust, University College Hospital
    London, NW12PG, United Kingdom
  • Royal Free London NHS Foundation Trust, Royal Free Hospital
    London, NW3 2QG, United Kingdom
  • Guys and St Thomas' NHS Foundation Trust, Guy's Hospital
    London, SE19RT, United Kingdom
  • The Royal Marsden NHS Foundation Trust, The Royal Marsden Hospital
    London, SW3 6JJ, United Kingdom
  • The Christie NHS Foundation Trust, Christie Hospital
    Manchester, M20 4BX, United Kingdom
  • The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital
    Newcastle Upon Tyne, NE7 7DN, United Kingdom
  • University Hospital Southampton NHS Foundation Trust, Southampton General Hospital
    Southampton, SO16 6YD, United Kingdom
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Oct 2, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 7, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03997474
Lead sponsor
Achilles Therapeutics UK Limited
Responsible party
Sponsor
First posted
Jun 25, 2019
Start date
Aug 15, 2019
Primary completion
Sep 3, 2024
Completion
Sep 3, 2024
Results posted
Mar 7, 2025
Last update
Mar 7, 2025

Study contacts

Medical Monitor, MD
study director · Achilles Therapeutics UK Limited

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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