Clinical trial NCT03711188: A Study of IMM-101 in Combination With Checkpoint Inhibitor Therapy in Advanced Melanoma
Official title: A Study of the Safety and Efficacy of IMM-101 in Combination With Checkpoint Inhibitor Therapy in Patients With Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Lead sponsor: Immodulon Therapeutics Ltd
Sponsor class: INDUSTRY
First posted: 2018-10-18
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and efficacy of the combination of IMM-101 with nivolumab.

Detailed description: 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.

Eligibility criteria: Key Inclusion Criteria:

1. Histologically-confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV) melanoma.
2. At least one measurable lesion by CT or MRI, according to RECIST 1.1.
3. Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) Performance Status of ≤1 at Day 0.
4. Known BRAF V600 mutation status or consent to BRAF V600 mutation testing during the Screening Period.
5. 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.
6. Patient is considered suitable for treatment with nivolumab.

For cohort A, the following key inclusion criteria apply:

1. 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:

1. 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:

1. Uveal/ocular melanoma.
2. 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.
3. Patient has documented history of clinically severe autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents.
4. 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:

1. 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:

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

Primary outcomes:
measure: Safety and Tolerability of the Combination of IMM-101 + Nivolumab
timeFrame: From the point of Informed Consent until end of the study assessment (up to 84 weeks) or until withdrawal from the study.
measure: Overall Response Rate
timeFrame: From enrollment to end of study (18 months) or withdrawal, whichever was soonest
Secondary outcomes:
measure: Best Overall Response (BOR) Using RECIST 1.1
timeFrame: 18 months
measure: Progression Free Survival (PFS)
timeFrame: From Visit 1 (week 0) and the first confirmation of progression using RECIST 1.1 (confirmed or unconfirmed), or death from any cause (whichever occurred first).
measure: Overall Survival (OS)
timeFrame: Overall survival was defined as the time from Visit 1 (week 0) until the end of the study (80 weeks) or until the date of death from any cause.
measure: Overall Survival (OS) at One Year
timeFrame: OS at 1 year was calculated after all patients had had the opportunity of 12 months treatment of study
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie Hospital
Study officials:
affiliation: St George's University Hospitals NHS Foundation Trust
name: Alberto Fusi
role: PRINCIPAL_INVESTIGATOR
References: