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

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

Sponsor considered no further meaningful data was being collected, nor were likely to be collected in the future.

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.

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.

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).

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).

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).

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.

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.

Blood samples were collected and sera prepared for analysis of immunological markers and mediators. Exploratory endpoints may include a change in one or more markers of immune status based on cellular involvement, function or cytokine/immune mediator production such as, for example, cytokines and antibodies, or any other clinically or immunologically relevant assays.

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.