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.
Inclusion Criteria:
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.
Part B2: Histologically proven cutaneous melanoma.
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:
Biologically male patients are eligible to participate in the trial if they meet one of the following criteria:
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
Exclusion Criteria:
Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C) and 4 weeks for investigational medicinal products) before treatment.
Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia/vitiligo, treated endocrinopathies (i.e. on physiological doses of endocrine replacement) or certain Grade 1 toxicities, which in the opinion of the Investigator and the CI should not exclude the patient.
Known untreated or active central nervous system (CNS) metastases (progressing or requiring corticosteroids for symptomatic control). Patients with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:
Major thoracic or abdominal surgery from which the patient has not yet recovered.
At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment
Has an active autoimmune disease that has required systemic treatment in past 3 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs) or is at risk of recurrence. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with a history of inflammatory bowel diseases such as Crohn's disease or ulcerative colitis will be excluded from the study. Patients with Sjogren's syndrome will not be excluded from the study.
Are receiving chronic systemic steroids (> 10 mg/day prednisone equivalent). Use of topical, inhalational, intranasal, and intraocular steroids will be permitted.
Patients that experienced a Grade 3 or higher immune-related AEs from prior treatment with immunotherapy will be excluded from the study.
Has received a live vaccine within 30 days of planned start of study therapy. Note: The inactivated virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.
Any of the following cardiac criteria:
Prior bone marrow transplant, allogenic tissue/solid organ transplant or have had extensive radiotherapy to greater than 25% of bone marrow within eight weeks.
Current malignancies of other types, with the exception of adequately treated cone biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. An exception to this criteria are cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for three years or more and are deemed at negligible risk for recurrence, are eligible for the trial.
Is a patient or plans to participate in another interventional clinical trial, whilst taking part in this study. Participation in an observational trial would be acceptable.
Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
Symptoms of COVID-19 and/or documented COVID-19 infection
Hypersensitivity to the active substance or to any of the IMP excipients
Active or known pre-existing or history of non-infectious/interstitial lung disease/pneumonitis
BLAZE@icr.ac.uk02034376301
Phase I will establish a recommended Phase 2 dose (RP2D) of Bexmarilimab in combination with Nivolumab
Phase II will assess the anti-tumour activity of bexmarilimab in combination with nivolumab
BLAZE@icr.ac.uk
anna.minchom@icr.ac.uk02086426011
An Investigational Immuno-therapy Study of BMS-986205 Given in Combination With Nivolumab and in Combination With Both Nivolumab and Ipilimumab in Cancers That Are Advanced or Have Spread
PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma
An Investigational Immuno-therapy Study of Experimental Medication BMS-986179 Given Alone and in Combination With Nivolumab
A Study of BMS-986253 in Combination With Nivolumab or Nivolumab Plus Ipilimumab in Advanced Cancers
An Investigational Study of Immunotherapy Combinations in Participants With Solid Cancers That Are Advanced or Have Spread
A Dose Escalation and Combination Immunotherapy Study to Evaluate BMS-986226 Alone or in Combination With Nivolumab or Ipilimumab in Patients With Advanced Solid Tumors
An Investigational Immuno-Therapy Study of Experimental Medication BMS-986242 Given in Combination With Nivolumab in Patients With Advanced Cancer
A Study of Nivolumab by Itself or Nivolumab Combined With Ipilimumab in Patients With Advanced or Metastatic Solid Tumors