A Long Term Follow up Study for Patients Who Previously Took Part in the Phase I Study IMM-101-001

Study Overview
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Brief Summary
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Patients who were previously enrolled in Study IMM-101-001 and who provided informed consent were eligible to participate in this study. Once eligibility was confirmed, a full medical history covering the period from completion of Study IMM-101-001 to date was taken. The treatment regimen with IMM-101 was one dose given every 4 weeks or as close to this interval as permitted due to practical or logistic considerations. The dose interval could be modified at the discretion of the Investigator provided the minimum period between doses was no less than 14 days. The overall objective was to determine the long term safety profile of IMM-101 administered intradermally for extended use.

Detailed Description
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This was an open-label long term follow up study. The study consisted of two phases: Screening and enrolment Patients, who provided informed consent participated in a screening period of up to 28 days to establish eligibility. Once eligibility was confirmed a full disease and treatment history covering the period from their completion of Study IMM-101-001 to date was taken. Treatment Patients could receive ongoing treatment every 4 weeks or as close to this interval as permitted due to practical or logistic considerations until death or withdrawal, unless such therapy was contraindicated, the patient did not wish to continue or the study was terminated by the Sponsor. At no point could the elapsed period between IMM-101 doses be less than 14 days. Patients could choose to withdraw from the study at any time and for any reason. IMM-101 could be stopped or the dosing regimen reduced if felt to be necessary by the Investigator and/or patient (e.g., intolerable injection site reactions). In the event of an injection site reaction of Grade 3 and above, and/or if significant ulceration, tenderness or lymphadenopathy was observed, at the discretion of the Investigator, patients could be administered a half dose of the study drug (i.e., a single 0.05 mL intradermal injection of IMM-101) or the timing of the injection could be delayed. If the dosing interval was increased, the patient still attended the study site for safety assessments preferably every 3 months but, if this was not possible, every 6 months at a minimum. The blood sample for exploratory analysis continued to be taken every 6 months. Any change in the dose of study drug administered or the frequency of dose administration was recorded in the patient's case report form (CRF). In the case of withdrawal, separate consent was sought to allow the continued collection on patient status.

Official Title
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An Open Label Long Term Follow up Study for Patients With Melanoma Who Were Previously Enrolled in the Phase I Study IMM-101-001

Conditions
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Malignant Melanoma

Intervention / Treatment
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* Biological: IMM-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient was previously enrolled in Study IMM-101-001 Patient gave consent to make their disease and treatment history for the intervening period between their completion of Study IMM-101-001 and enrollment in this study available to the Sponsor Patient gave signed informed consent for participation in the study Exclusion Criteria: Female patient of child-bearing potential who was not, in the opinion of the Investigator, using an approved method of birth control (e.g., physical barrier [patient and partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device [IUD]). Those patients that utilised hormonal contraceptives must have used the same method for at least three months before additional barrier contraception (as described above) was discontinued from being used concomitantly with the hormonal contraception. Patient of non-child-bearing potential were defined as having 12 month amenorrhoea or were surgically sterile. Female patient who was pregnant, breast feeding or planning a pregnancy during the course of the study. A pre-treatment urine pregnancy test measuring human chorionic gonadotrophin (hCG) must be negative. Patient was unable or unwilling to comply with the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMM-101<br>IMM-101 1.0 mg administered intradermally | Biological: IMM-101<br>* IMM-101 10mg/mL, a suspension of heat-killed whole cell M. obuense in borate-buffered saline.<br>* Other names: Heat-killed whole cell M. obuense;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events With a Causal Relationship to IMM-101 | Adverse events measured throughout the study and assessed for severity using NCI CTCAE and causality to measure the profile and number of local and systemic toxicities. Treatment related Adverse Events were defined as being definitely, probably or possibly related to IMM-101 or with an unknown relationship. | From the time of signing informed consent until 30 days after the end of study or withdrawal, a median of 4.4 years (range 1.2 to 6.7). | 
| Treatment Emergent Adverse Events of NCI CTCAE ≥Grade 3 | Adverse events measured throughout the study and assessed for severity using NCI CTCAE and causality to measure the profile and number of local and systemic toxicities | From the time of signing informed consent until 30 days after the end of study or withdrawal, a median of 4.4 years (range 1.2 to 6.7). | 
| Treatment Emergent Serious Adverse Events | Adverse events measured throughout the study and assessed for severity using NCI CTCAE and causality to measure the profile and number of local and systemic toxicities. There were no IMM-101 related serious adverse events reported during the study. | From the time of signing informed consent until 30 days after the end of study or withdrawal, a median of 4.4 years (range 1.2 to 6.7). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Overall survival | Overall survival was defined as the time from enrolment until date of death for up to 81 months. Patients still alive after 81 months were censored at withdrawal from the study or at last known date alive if later. | 
| Incidence of Change in Metastatic Disease | The protocol required any change in metastatic disease to be documented where possible. However, given this was a real-life long-term follow-up study, CT or MRI scans were not mandated as part of the protocol and were only performed as clinically indicated. Very few scans were performed during the course of the study (0 to nine events per patient). Given the fact patients could receive anti-cancer therapy on study, disease status fluctuated throughout the study (better, worse, no change). This coupled with the sparsity of CT or MRI scan data collected on a per patient basis resulted in only Best Overall Response being described. | From Informed Consent to death or withdrawal (median 4.4 years, range 1.2 - 6.7) |