Pan tumour trial of COX-inhibitor and immune checkpoint blockade
Triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC)
Current interventions as of 07/05/2026: Interventions: ALL cohorts IMP: Celecoxib Form: Capsule Dose: 200 mg twice daily for 13 weeks then 100 mg twice daily (continuous until disease progression or stopping immune therapy) Route: Oral TNBC: IMP: Atezolizumab Form: Solution for infusion Dose: 840 mg on day 1 and day 15 of a 28-day cycle (until disease progression or unacceptable toxicity; patients who are no longer also receiving concurrent Nab-paclitaxel can receive 1680mg d1 of a 28-day cycle or 1875mg subcutaneously day 1 of a 21-day cycle) Route: intravenous (IV) IMP: Nab-paclitaxel Form: Powder for suspension for infusion Dose: 100 mg/m² day 1,8,15 of a 28-day cycle (continuous until disease progression) Route: IV RCC: IMP: Nivolumab Form: Concentrate for solution for infusion Dose: 3 mg/kg every 21 days for the first four cycles and then flat dosed at 480 mg every 28 days (continuous until disease progression) Route: IV IMP: Ipilimumab Form: Concentrate for solution for infusion Dose: 1 mg/kg every 21 days for the first four cycles Route: IV NSCLC: IMP: Pembrolizumab Form: Solution for infusion Dose: 200 mg every 21 days or 400 mg every 42 days (maximum treatment duration 2 years) Route: IV Duration of treatment: All patients will be treated until progressive disease, unacceptable toxicity, end of trial or withdrawal of patient consent. In the case of pembrolizumab patient must also stop treatment after 2 years of therapy in line with national guidelines. Duration of follow-up: For all cohorts a minimum follow-up of 6 months for all patients who do not experience progression prior to 6 months post start of treatment Overall study duration: 48 months Screening/baseline activity: 1. Written Informed Consent for the LION trial 2. Confirmation of histological diagnosis of tumour type and patient eligibility check. 3. Complete demographics and medical history including prior surgeries, systemic therapies, radiotherapy, and allergies 4. Full physical exam
Current key inclusion criteria as of 07/05/2026: All cohorts: 1. Written informed consent obtained 2. Age ≥ 18 years at the time of screening. 3. No prior treatment for metastatic or locally advanced, incurable disease. 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment. 5. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline. 6. Adequate organ and bone marrow function as defined below 6.1. Haemoglobin ≥ 9.0 g/dL 6.2. Absolute neutrophil count ≥ 1.5 x 10^9/l 6.3. Platelet count ≥ 100 x 10^9/l 6.4. Serum bilirubin ≤ 1.5 x ULN. In patients with a confirmed diagnosis of Gilbert’s syndrome then an isolated bilirubin of ≤ 3 x ULN is permitted. 6.5. ALT and AST ≤ 2.5 x ULN 6.6. Creatinine clearance ≥ 40mL/min calculated by Cockcroft-Gault (using actual body weight) OR by measured 24-hour urine collection. 7. Provision of an FFPE tumour sample taken within 12 months of trial registration. 8. Eligible for immune-checkpoint blockade therapy according to the relevant Blueteq/NHSE eligibility criteria with approval requested and confirmed. 9. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of the study drug (see definition in section 10.4). 10. WOCBP must agree to follow instructions in Section 8.3.2 for method(s) of contraception for the duration of treatment with study drugs plus 5 months after the completion of trial therapy. 11. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment plus 5 months after completion of treatment. 12. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, participating WOCBP must still undergo pregnancy testing. Tumour-specific inclusion criteria: Triple Negative Breast
Current participant exclusion criteria as of 14/05/2024: All cohorts: 1. History of another malignancy within the last 5 years except adequately treated non-melanoma skin cancer; curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS); stage 1, grade I endometrial carcinoma. 2. History of leptomeningeal metastases 3. Known symptomatic CNS metastases or symptoms suspicious of CNS metastases are excluded unless: 3.1. Symptomatic lesions have been definitively treated with surgery or stereotactic surgery (whole-brain radiation may be given as adjuvant treatment), and do not require steroids for control of symptoms 3.2. Are asymptomatic without the use of steroids. 4. Current use of a prohibited medication as described in section 9.7.2. 5. Patients known to be CYP2C9-poor metabolisers. 6. Has received a live vaccine within 30 days of the first dose of study treatment. 7. Contraindications to COX-inhibitor dosing including hypersensitivity. 8. Hypersensitivity to sulphonamides. 9. Significant cardiovascular disease including a history of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months or clinically significant congestive heart failure. 10. Any other serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that in the opinion of the investigator could interfere with the patient’s safety, obtaining informed consent, or compliance with study procedures. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection. 12. Patients with active, known or suspected autoimmune disease. The following are exceptions to this criterion: 12.1. Patients with vitiligo or alopecia 12.2. Patients with hypothyroidism stable on hormone replacement 12.3. Patients with any chronic skin condition that does not require systemic therapy 13. Patients with a condition requ