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

A Study of the Safety and Efficacy of IMM-101 in Combination With Checkpoint Inhibitor Therapy in Patients With Advanced Melanoma

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

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: Nivolumab; Drug: Ipilimumab; Drug: IMM-101

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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW17 0QT
    • St George's University Hospitals NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: IMM-101 (and nivolumab or ipilimumab); Patients in cohort A were given IMM-101 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 Names: 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 Names: 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.; Other Names: Heat killed whole cell M. obuense National Collection of Type Cultures (NCTC) 13365

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of the Combination of IMM-101 + Nivolumab	Incidence, frequency and severity of treatment emergent adverse events (TEAEs) throughout the study.	From the point of Informed Consent until end of the study assessment (up to 84 weeks) or until withdrawal from the study.
Overall Response Rate	The primary endpoint of Overall Response Rate (ORR) is defined as the number of subjects with a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) divided by the number of subjects in the Intent-to-treat analysis set in each cohort of the study. The BOR will be determined once all the data up to and including the 12-month assessments for Cohort A or the 6-month assessment for Cohort B are available. It is defined as the best response designation based on confirmed responses determined by the investigator according to RECIST 1.1, recorded between the date of first postscreening scan and the date of last scan at/prior to the assessment at the 12-month assessment (Cohort A) and 6-month assessment/last assessment prior to change of treatment to IMM-101 + ipilimumab whichever is sooner (Cohort B).	From enrollment to end of study (18 months) or withdrawal, whichever was soonest

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response (BOR) Using RECIST 1.1	Best Overall Response (BOR) is defined as the best response (complete or partial response, stable disease or progressive disease) designation based on confirmed responses determined by the investigator according to RECIST 1.1, recorded between the date of first postscreening scan and the date of last scan at/prior to the assessment at the 12-month assessment (Cohort A) and 6-month assessment/last assessment prior to change of treatment to IMM-101 + ipilimumab whichever is sooner (Cohort B).) Patients in cohort B who changed therapy without documented progression were censored at their last scan assessment prior to the change of therapy.	18 months
Progression Free Survival (PFS)	Progression-free survival was defined as the time from Visit 1 (week 0) to the first confirmation of progression using RECIST 1.1 (confirmed or unconfirmed), or death from any cause (whichever occurred first). Progression was determined by the investigator using the CT or MRI scan or death due to any cause. Patients who died without reporting progression were considered to have progressed on the date of their death. Progression is defined by RECIST 1.1 guidelines as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.	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).
Overall Survival (OS)	Overall survival was defined as the time from Visit 1 (week 0) until date of death from any cause. OS was calculated for the entire study duration, where patients without a death date were right censored at the date the patient was last known to be alive. Post-study survival information was collected until database lock, for subjects completing or withdrawing from the study and included in the analysis.	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.
Overall Survival (OS) at One Year	Number of patients surviving at leat 12 months	OS at 1 year was calculated after all patients had had the opportunity of 12 months treatment of study

Collaborators and Investigators

• Sponsor: Immodulon Therapeutics Ltd
• Investigators: Principal Investigator: Alberto Fusi, St George's University Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2018
• Primary Completion (Actual): December 2, 2021
• Study Completion (Actual): December 2, 2021

Study Registration Dates

• First Submitted: October 4, 2018
• First Submitted That Met QC Criteria: October 16, 2018
• First Posted (Actual): October 18, 2018

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: IMM-101-015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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