A Phase I/II Trial of Bexmarilimab and Nivolumab in Patients With Solid Tumours, Non-Small Cell Lung Cancer and Melanoma
The trial will test if the combination of bexmarilimab and nivolumab can help patients whose cancers have stopped responding to immunotherapy treatment. It will focus on two cancers: non-small cell lung cancer and melanoma. Early research suggests bexmarilimab may change some immune cells inside the tumour so they create a stronger attack signal, which could help other immune cells recognise and kill cancer cells more effectively. This may make it easier for PD-1 immunotherapy drugs to work again by helping the immune system stay active against the tumour. This is a Phase I/II clinical trial. In Phase I, researchers will give increasing doses of bexmarilimab together with a standard (fixed) dose of nivolumab to patients with solid tumours, to find the safest and most suitable dose to use going forward (the recommended Phase 2 dose). In Phase II, the study will treat two groups of patients-one with non-small cell lung cancer and one with melanoma-using that selected dose.
• Part A:
• Histologically proven solid tumour, refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient
• Part B1: Histologically proven NSCLC.
⁃ Patient has received at least one but not more than three lines of systemic anticancer therapy for metastatic disease.
⁃ Patient has received at least two cycles of immune checkpoint inhibitor and has demonstrated disease progression within 12 weeks of last dose.
⁃ Patient has had a benefit to prior immune checkpoint inhibitor defined as greater than 6 months of treatment or partial response.
⁃ Patients with actionable EGFR, ALK, or other known genomic alterations must have received at least 1 relevant targeted therapy treatment if available.
• Part B2: Histologically proven cutaneous melanoma.
⁃ Patient has received at least one but not more than three lines of systemic anticancer therapy for metastatic disease.
⁃ Patient has received at least two cycles of immune checkpoint inhibitor and has demonstrated disease progression within 12 weeks of last dose.
⁃ Patients with BRAF mutations must have received relevant targeted therapy.
⁃ Patient has had a benefit to prior immune checkpoint inhibitor defined as greater than 6 months of treatment or partial response
• Life expectancy of at least 12 weeks
• World Health Organisation (WHO) performance status of 0-1 (Appendix 2)
• Measurable disease as assessed by iRECIST
• Biologically female patients are eligible to participate in the trial if they are not pregnant, not breast feeding and meet one of the following criteria:
∙ a biological woman of childbearing potential (WOCB) who has a negative serum or urine pregnancy test before enrolment and agrees to use a highly effective form of contraception (refer to Appendix 3) from signing the consent form, throughout the trial and for six months afterwards. A biological woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
‣ A biological woman of non-childbearing potential; a postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in biological women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
• Biologically male patients are eligible to participate in the trial if they meet one of the following criteria:
∙ is fertile and agrees to use and ensure their partners (if WOCBP) use a highly effective form of contraception (refer to Appendix 3) from signing the consent form, throughout the trial and for six months afterwards. Biological men with pregnant or lactating partners must be advised to use barrier method contraception (refer to Appendix 3) to prevent exposure of the foetus or neonate; a biological man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy
‣ is infertile
• Negative serology for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV)
• Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day 1) prior to the patient's first dose of IMP
• Laboratory Test Value required Haemoglobin (Hb) ≥ 9.0 g/dL Absolute neutrophil count ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L
• Serum bilirubin ≤ 1.5 x ULN; with the following exception:
• Patients with known Gilbert disease who have serum bilirubin level ≤ 3 × ULN may be enrolled
• ALT ≤ 2.5 x ULN unless raised due to tumour in which case up to 5 x ULN is permissible AST ≤ 2.5 x ULN unless raised due to tumour in which case up to 5 x ULN is permissible Renal function Calculated creatinine clearance (using the Wright, Cockcroft \& Gault formula) Glomerular filtration rate ≥ 30 mL/min (uncorrected value)
• 18 years or over
⁃ Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up