Investigating the Combination of Bexmarilimab and Nivolumab in Solid Tumours, Melanoma and NSCLC (BLAZE)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Non Small Cell Lung Cancer; Melanoma (Skin Cancer); Solid Tumor in Advanced Stage
• Intervention / Treatment: Drug: Bexmarilimab 1mg/kg and nivolumab 1mg/kg; Drug: Bexmarilimab 3mg/kg and nivolumab 1mg/kg; Drug: Recommended Phase II Dose

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Aasia Hussain, PhD; Phone Number: 02034376301; Email: BLAZE@icr.ac.uk
• Study Contact Backup: Name: Anna Zachariou, PhD; Email: BLAZE@icr.ac.uk

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
    • Contact: Dr Donna Graham; Phone Number: 01619187262; Email: donna.graham8@nhs.net
    • Principal Investigator: Dr Donna Graham
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust - Drug Development Unit
    • Contact: Dr Anna Minchom; Phone Number: 02086426011; Email: anna.minchom@icr.ac.uk
    • Principal Investigator: Dr Anna Minchom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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
2. Life expectancy of at least 12 weeks
3. World Health Organisation (WHO) performance status of 0-1 (Appendix 2)
4. Measurable disease as assessed by iRECIST

5. 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:

   1. 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.
   2. 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.

6. Biologically male patients are eligible to participate in the trial if they meet one of the following criteria:

   1. 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
   2. is infertile
7. Negative serology for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV)

8. 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)

9. 18 years or over
10. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up

Exclusion Criteria:

1. 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.
2. 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.

3. 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:

   • Evaluable or measurable disease outside the CNS is present.
   • Radiographic stability upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the baseline disease assessment
   • Not requiring corticosteroids.
4. Major thoracic or abdominal surgery from which the patient has not yet recovered.
5. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
6. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus.
7. 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
8. 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.
9. Are receiving chronic systemic steroids (> 10 mg/day prednisone equivalent). Use of topical, inhalational, intranasal, and intraocular steroids will be permitted.
10. Patients that experienced a Grade 3 or higher immune-related AEs from prior treatment with immunotherapy will be excluded from the study.
11. 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.

12. Any of the following cardiac criteria:

    • Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 consecutive electrocardiograms (ECGs) within 5 minutes of each other.
    • Known congenital QT syndrome or history of torsades de pointes. Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG, e.g. complete left bundle branch block, third degree heart block. Controlled atrial fibrillation is allowed.
    • Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association [NYHA Grade 2 or above], severe valvular disease, uncontrolled hypertension despite optimal therapy.
13. Prior bone marrow transplant, allogenic tissue/solid organ transplant or have had extensive radiotherapy to greater than 25% of bone marrow within eight weeks.
14. 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.
15. 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.
16. Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
17. Symptoms of COVID-19 and/or documented COVID-19 infection
18. Hypersensitivity to the active substance or to any of the IMP excipients
19. Active or known pre-existing or history of non-infectious/interstitial lung disease/pneumonitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I: Dose Escalation; Phase I will establish a recommended Phase 2 dose (RP2D) of Bexmarilimab in combination with Nivolumab	Drug: Bexmarilimab 1mg/kg and nivolumab 1mg/kg; Dose Level 1; Drug: Bexmarilimab 3mg/kg and nivolumab 1mg/kg; Dose Level 2
Experimental: Phase II: Dose Expansion; Phase II will assess the anti-tumour activity of bexmarilimab in combination with nivolumab	Drug: Recommended Phase II Dose; Recommended Phase II Dose of bexmarilimab in combination with nivolumab established from Dose Escalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To establish a recommended Phase II dose (RP2D) of bexmarilimab in combination with nivolumab	At the end of Cycle 2 (Cycle 1 is 28 days and Cycle 2 is 21 days)".
Determining causality of each adverse event to bexmarilimab and nivolumab and grading severity according to the NCI CTCAE Version 5.0	From the start of treatment until the end of the trial (due to documented disease progression or withdrawal of consent or toxicity), with follow-up continuing for 28 days after the last dose of the IMP.
Evaluation of disease response by RECIST criteria version 1.1, immune-modified RECIST (iRECIST) and thus overall response rate	From date of enrolment until the date of first documented progression, assessed up to 48 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluation of disease response by RECIST criteria version 1.1, iRECIST and thus response rate, clinical benefit rate, radiological PFS and overall survival.	From date of enrolment until the date of first documented progression, assessed up to 48 months
Determination of changes in markers of target inhibition and immune microenvironment in tumour and blood.	48 months

Collaborators and Investigators

• Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: Royal Marsden NHS Foundation Trust; The Christie NHS Foundation Trust; Faron Pharmaceuticals Ltd
• Investigators: Study Director: Dr Anna Minchom, MB BCh, FRCP, MD (Res), Institute of Cancer Research, United Kingdom

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 31, 2030
• Study Completion (Estimated): January 31, 2030

Study Registration Dates

• First Submitted: July 7, 2026
• First Submitted That Met QC Criteria: July 17, 2026
• First Posted (Actual): July 21, 2026

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Non-Small-Cell Lung; Melanoma; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; bexmarilimab
• Other Study ID Numbers: CCR6142

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No