A Study of IMM-101 in Combination With Checkpoint Inhibitor Therapy in Advanced Melanoma

This open-label study will assess the safety and efficacy of the combination of IMM-101 with nivolumab in patients with unresectable stage III, or stage IV melanoma who are either treatment-naive (cohort A) or whose disease has progressed during PD-1 blockade (cohort B). Ipilimumab may be used as a subsequent treatment in place of nivolumab alongside IMM-101 for patients in cohort B if their disease progresses on study. Eighteen patients will be enrolled into cohort A and 8 patients into cohort B.

Key Inclusion Criteria:

• Histologically-confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV) melanoma.
• At least one measurable lesion by CT or MRI, according to RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) Performance Status of ≤1 at Day 0.
• Known BRAF V600 mutation status or consent to BRAF V600 mutation testing during the Screening Period.
• Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration (Week 0, Visit 1). Prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to enrolment (Week 0, Visit 1), and all related adverse events have resolved or stabilised.
• Patient is considered suitable for treatment with nivolumab.

For cohort A, the following key inclusion criteria apply:

• Patient is treatment-naive (i.e. no prior systemic anticancer therapy for unresectable or metastatic melanoma).

For cohort B, the following key inclusion criteria apply:

• Patient is either currently receiving treatment with an anti-PD-1 therapy (monotherapy or in combination with ipilimumab), for advanced melanoma and has progressive disease by RECIST 1.1 after 4 or more doses; or has previously received at least 4 doses of PD-1 targeted therapy, alone or in combination with ipilimumab, had disease progression by RECIST 1.1 during this therapy and has not received any further therapy for advanced melanoma.

Key Exclusion Criteria:

• Uveal/ocular melanoma.
• Active brain metastases or leptomeningeal metastases. Patients with brain metastases are eligible for cohort B of the study only, if these have been treated and there is no MRI evidence of progression for at least 8 weeks after treatment is complete and within 21 days prior to first dose of study treatment administration.
• Patient has documented history of clinically severe autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents.
• Patient has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressant drugs (such as azathioprine, tacrolimus, cyclosporin) within the 14 days period before the first administration of IMM-101.

For cohort A, patients meeting the following key criteria are also ineligible to participate in this study:

• Patient has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD ligand-1 (PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agent.

For cohort B, patients meeting the following key criteria are also ineligible to participate in this study:

• Patient has received more than one treatment regimen for advanced (stage III/IV) disease prior to their anti PD-1 therapy.