IMM-101-015: IMM-101 in Combination with Checkpoint Inhibitor Therapy
Research type
Research Study
Full title
A Study of the Safety and Efficacy of IMM-101 in Combination with Checkpoint Inhibitor Therapy in Patients with Advanced Melanoma
IRAS ID
244789
Contact name
Alberto Fusi
Contact email
Sponsor organisation
Immodulon Therapeutics Ltd
Eudract number
2018-001346-34
Duration of Study in the UK
2 years, 8 months, 0 days
Research summary
Summary of Research
IMM-101 is an immune therapy, with promising efficacy signals demonstrated in patients with metastatic pancreatic cancer and in some patients with advanced melanoma. IMM-101 contains a specific organism (Mycobacterium obuense) that has been killed at high temperature so that it is not infectious, but still can produce immunological effects.
The target population for this study are patients with metastatic melanoma whose disease cannot be completely removed through surgery, and who are either previously untreated (cohort A), or whose disease has progressed during treatment with a PD-1 inhibitor (cohort B).
Patients will receive treatment with PD-1 inhibitor, nivolumab, according to the prescribing information for nivolumab, plus the investigational drug IMM-101. Patients in cohort B who experience progression during the study may change to receiving treatment with ipilimumab, if deemed by the investigator to be in the best interests of the patient.
Patients will receive IMM-101 every 2 weeks for the first 3 doses, followed by a rest period of 4 weeks, then patients will receive IMM-101 every 2 weeks for the next 3 doses, and thereafter every 4 weeks.
Patients will continue to receive IMM-101 on study until unacceptable side-effects, the investigator's decision to discontinue treatment, withdrawal of patient consent or 18 months study treatment, whichever is the sooner.
Patients completing or withdrawing from the study will be followed up for post-study survival information until database lock.
Summary of Results
Study IMM-101-015 investigated the safety and efficacy of IMM 101 in combination with a type of approved melanoma treatment called checkpoint inhibitors.
The study enrolled patients with advanced stage disease which had spread to multiple sites within the body and could not be removed by surgery. Two different groups of patients were eligible; patients who had not received any prior treatment for their disease (Cohort A) and patients whose disease had progressed despite treatment with Nivolumab (Cohort B).
Although it was planned to enroll 18 cohort A patients and 8 cohort B patients, recruitment was suspended at both study sites in March 2020 due to the COVID-19 pandemic prior to reaching the planned number of enrolled patients, however, all recruited patients had the opportunity for 18 months treatment on study and were followed to study completion/withdrawal. Eleven patients were recruited to Cohort A and five were recruited to Cohort B.
For all patients, Nivolumab was given as specified in the prescribing information and IMM 101 was given initially every 2 weeks and then every 4 weeks for up to 18 months. For patients in Cohort B who failed to respond to treatment with IMM-101 + nivolumab there was an option to change treatment on study to IMM-101 + ipilimumab (another type of checkpoint inhibitor).
All patients were followed for assessment of safety, response to treatment (via scheduled CT scans or MRI) and survival. All available safety data were reviewed by the Sponsor and Investigator every 6 months throughout the study.
The study was conducted at two hospitals within the UK.
Patients in cohort A were treated with IMM-101 and/or nivolumab for between 1 and 18 months. Patients in cohort B were treated with IMM-101 and/or nivolumab for between 1 and 6.5 months. One cohort B patient also received one dose of ipilimumab.
Safety
Consistent with previous clinical studies, IMM-101 was generally well tolerated in this group of patients. There were no serious side effects leading to death and only one patient withdrew from the study due to side effects of the treatment. Six patients experienced side effects which were classified as serious but none of these side effects were considered to be caused by IMM 101. Most serious side effects were resolved or resolving by the end of the study, except for swallowing difficulties, constant tiredness and lack of energy which were ongoing at the time of tone patient’s death due to disease progression.
The most commonly reported non-serious side effects were rash (reported by 44% patients), constant tiredness (reported by 38% patients), redness at the injection site and itchy skin (each reported by 25% patients), and diarrhoea and injection site swelling (each reported by 19% patients).
The majority of side effects related to IMM-101 were local reactions at the injection site. The majority of all injection site reactions were mild or moderate and did not require any form of treatment. Only two patients experienced a severe injection site reaction.
Overall, IMM-101 was well tolerated in these patients in terms of injection site reactions and other side effects. No serious side effects were assessed to be related to IMM-101.
Effectiveness of treatment
The main endpoint of the study was to assess the number of patients who responded to the treatment using standard criteria to assess the size of the tumour – this is known as the Overall Response Rate. Response to treatment included patients whose tumour disappeared completely those whose tumour shrank in size but was still detectable. In Cohort A eight of the eleven patients responded to treatment so the Overall Response Rate was 73%. In Cohort B, none of the 5 patients responded to treatment so the Overall Response Rate was zero.
In Cohort A. there was no difference in response to treatment between patients who had high levels of a tumour protein called PD-L1 and those who had low or undetectable levels.
Another endpoint was the time each patient survived before their tumour progressed – known as Progression Free Survival. In Cohort A progression free survival ranged from <3 months to >18 months. In Cohort B, no patients responded to treatment so progression free survival could not be calculated.
This study also evaluated the length of time patients survived overall irrespective of whether they responded to treatment or not. In Cohort A, 90% of patients survived at least 6 months and 81% of patients survived at least 18 months. In Cohort B, all patients survived at least 6 months but no patients survived for 18 months.
The overall response rate in this study compares favourably to the results of a previous study in 316 similar patients who were treated with nivolumab alone (the CheckMate 067 study). However, the small number of patients in this non-comparative study means that no firm conclusions can be reached about of effectiveness of the combination of IMM-101 and nivolumab. The encouraging findings from this study need to be confirmed in larger studies.REC name
London - Westminster Research Ethics Committee
REC reference
18/LO/1069
Date of REC Opinion
27 Jul 2018
REC opinion
Further Information Favourable Opinion