A first-in-human clinical trial in adult patients with advanced non-small cell lung cancer of a personalised therapy targeting specific mutations that occur in all cancer cells within a single patient.

Phase 1

• Conditions: on-small cell lung cancer; MedDRA version: 21.1Level: PTClassification code 10001245Term: Adenosquamous cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10001246Term: Adenosquamous cell lung cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10001247Term: Adenosquamous cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10001251Term: Adenosquamous cell lung cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10001252Term: Adenosquamous cell lung cancer stage IIIASystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10001253Term: Adenosquamous cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10001254Term: Adenosquamous cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10023774Term: Large cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10069730Term: Large cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2018-001005-85-FR
• Lead Sponsor: Achilles Therapeutics Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-18
• Last Update Posted: 10 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Inclusion criteria will apply at multiple timepoints.

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 or cytologically 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 x10^9/L.
c. Absolute Neutrophil Count (ANC) = 1.5 x10^9/L.
d. Platelets = 100 x10^9/L.
e. PT and APTT < 1.5x ULN (unless receiving therapeutic anticoagulation).
f. AST or ALT = 2.5x ULN.
g. Bilirubin < 1.5x ULN (< 3x ULN in Gilbert’s Syndrome).
h. Creatinine clearance/estimated glomerular filtration rate (GFR) = 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. Refer to Appendix F for pregnancy testing requirements in Germany. Patients with female partners of childbearing potential must agree to use adequate contraception for at least 6 months after the ATL001 infusion. 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 (IIIB/IV) newly diagnosed disease 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 or recurred following standard of care therapies, or if they cannot tolerate standard of care therapies – see inclusion number 11).
b. Patients with advanced stage (IIIB/IV) disease 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 have locally advanced unresectable or metastatic NSCLC whose disease has progressed or recurred following standard of care or who are ineligible for, or who cannot tolerate, standard of care therapies, e.g. platinum-based chemotherapy and an immune checkpoint inhibitor.
12. Patients must have measurable disease according to RECIST v1.1 criteria prior to lymphodepletion. (If patients have no measurable disease following standard therapy, lymphodepletion and ATL001 treatment may be delay

Exclusion Criteria

Exclusion criteria will apply at multiple timepoints.

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 < 100 cigarettes in their lifetime, per WHO criteria).
4. Patients for whom there is documented evidence of an actionable tumour driver oncogene mutation (e.g. EGFR, ALK or ROS-1) at the time of initial screening.
5. Patients with active autoimmune disease requiring immunosuppressive treatments.
6. Patients requiring regular treatment with steroids at a dose higher than prednisolone 10 mg/day (or equivalent).
7. Patients with superior vena cava syndrome.
8. Patients with a current or recent history, as determined by the Investigator, of clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.
9. Patients with a history of immune mediated central nervous system toxicity that was caused by, or suspected to be caused by, immunotherapy.
10. Patients who are pregnant or breastfeeding.
11. Patients who have undergone major surgery in the previous 3 weeks.
12. 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).
13. Patients with a history of organ transplantation.
14. Patients who have previously received any investigational cell or gene therapies.
15. Patients with contraindications for cyclophosphamide, fludarabine and IL-2 at per protocol doses (see Investigator’s Brochure for details).
16. Patients who have received any cytotoxic chemotherapy or anti-angiogenesis agent within the 3 weeks prior to tissue and blood procurement.
17. Patients with evidence of disease progression at the first scan after commencing standard first line therapy (i.e. refractory disease).
18. 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:
19. Patients with any contraindications for pembrolizumab (Refer to the latest available prescribing information (e.g. SmPC) or the Investigator’s Brochure for safety information for pembrolizumab).
All exclusion criteria except 2, 3, 4, 16 and 17 will apply again to all patients prior to lymphodepletion for treatment with ATL001:
In addition, the following criteria will apply:
20. Patients who have received a live vaccination within the 28 days prior to lymphodepletion.
21. Patients with an active infection requiring antibiotics.
22. Patients who have received any cytotoxic chemotherapy within the 3 weeks prior to lymphodepletion.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified