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

NCT07718243 | Not Yet Recruiting Phase 1

• 1 other identifier: CCR6142
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Melanoma (Skin Cancer); Non Small Cell Lung Cancer; Solid Tumor in Advanced Stage

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• 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

Study Arms (2)

Phase I: Dose Escalation

EXPERIMENTAL

Phase I will establish a recommended Phase 2 dose (RP2D) of Bexmarilimab in combination with Nivolumab

Drug: Bexmarilimab 1mg/kg and nivolumab 1mg/kg; Drug: Bexmarilimab 3mg/kg and nivolumab 1mg/kg

Phase II: Dose Expansion

EXPERIMENTAL

Phase II will assess the anti-tumour activity of bexmarilimab in combination with nivolumab

Drug: Recommended Phase II Dose

Interventions

Bexmarilimab 3mg/kg and nivolumab 1mg/kg DRUG

Dose Level 2

Phase I: Dose Escalation

Recommended Phase II Dose DRUG

Recommended Phase II Dose of bexmarilimab in combination with nivolumab established from Dose Escalation

Phase II: Dose Expansion

Bexmarilimab 1mg/kg and nivolumab 1mg/kg DRUG

Dose Level 1

Phase I: Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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.
• 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:

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Faron Pharmaceuticals Ltd: collaborator
• The Christie NHS Foundation Trust: collaborator
• Royal Marsden NHS Foundation Trust: collaborator

Study Sites (2)

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

The Royal Marsden NHS Foundation Trust - Drug Development Unit

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung

Interventions

bexmarilimab; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dr Anna Minchom, MB BCh, FRCP, MD (Res)

  Institute of Cancer Research, United Kingdom

  STUDY DIRECTOR

Central Study Contacts

Aasia Hussain, PhD

CONTACT

02034376301; BLAZE@icr.ac.uk

Anna Zachariou, PhD

CONTACT

BLAZE@icr.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2026
• First Posted: July 21, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): January 31, 2030
• Study Completion (Estimated): January 31, 2030
• Last Updated: July 21, 2026

Record last verified: 2026-07

Locations

GB (2)