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

Study Description

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Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Melanoma	Drug: Nivolumab; Drug: Ipilimumab; Drug: IMM-101	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	26 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Study of the Safety and Efficacy of IMM-101 in Combination With Checkpoint Inhibitor Therapy in Patients With Advanced Melanoma
Actual Study Start Date :	October 4, 2018
Estimated Primary Completion Date :	July 1, 2021
Estimated Study Completion Date :	July 1, 2021

Arms and Interventions

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Arm

Intervention/treatment

Experimental: IMM-101 (and nivolumab or ipilimumab); IMM-101 given in combination with nivolumab. Patients in cohort B who fail to respond to treatment with IMM-101 and nivolumab, and who meet certain criteria, have the option to change treatment on study to IMM-101 and ipilimumab.

Drug: Nivolumab; Nivolumab is to be administered as a 3 mg/kg IV infusion every two weeks in accordance with the prescribing information.; Other Name: Opdivo; Drug: Ipilimumab; Ipilimumab, when used as subsequent treatment for patients in cohort B, is to be administered as a 3 mg/kg IV infusion over 90 minutes every three weeks for a maximum of 4 doses, in accordance with the prescribing information.; Other Name: Yervoy; Drug: IMM-101; A single 0.1 mL intradermal injection of IMM 101 (10 mg/mL) given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter.

Outcome Measures

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Primary Outcome Measures :

1. Overall Response Rate (ORR) using RECIST 1.1 [ Time Frame: 18 months ]
   ORR is calculated from Best Overall Response recorded during treatment with IMM-101 + nivolumab
2. The profile of adverse events experienced [ Time Frame: 18 months ]

Secondary Outcome Measures :

1. Progression free survival (PFS) [ Time Frame: 18 months ]
2. Overall survival (OS) [ Time Frame: Approximately 30 months ]
3. Overall survival (OS) at one year [ Time Frame: 12 months ]
4. Patients with values outside normal range and within normal range at post baseline assessments [ Time Frame: 18 months ]
5. Local tolerability measured as injection site reactions [ Time Frame: 18 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Contacts

Contact: Alberto Fusi	+44 (0) 208 725 2425	alberto.fusi@stgeorges.nhs.uk

Locations

United Kingdom
St George's University Hospitals NHS Foundation Trust	Recruiting
London, United Kingdom, SW17 0QT
Contact: Alberto Fusi +44 (0) 208 725 2425 alberto.fusi@stgeorges.nhs.uk
Principal Investigator: Alberto Fusi

Sponsors and Collaborators

Immodulon Therapeutics Ltd

Investigators

Principal Investigator:	Alberto Fusi	St George's University Hospitals NHS Foundation Trust

More Information

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Responsible Party:	Immodulon Therapeutics Ltd
ClinicalTrials.gov Identifier:	NCT03711188 History of Changes
Other Study ID Numbers:	IMM-101-015
First Posted:	October 18, 2018
Last Update Posted:	October 18, 2018
Last Verified:	October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue	Nevi and Melanomas; Nivolumab; Antibodies, Monoclonal; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs