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A phase II study to evaluate the safety and efficacy of IMM-101 in combination with checkpoint inhibitors in patients with advanced melanoma: final results of the IMM-101-015 trial

2nd June 2022

The incidence of malignant melanoma is reported to be increasing every year, both globally and in the UK. Treatment options have increased in recent years with the development of immunotherapies (ipilimumab, nivolumab and pembrolizumab) and targeted therapies blocking BRAF and MEK. IMM-101 is a suspension of heat-killed whole cell Mycobacterium obuense, which enhances the innate immune response and dendritic cell maturation. In animal models, it increases antigen specific responses and number of CD8+ CTL and CD4 + Th1 cells. An important feature of the mode of action of IMM-101 is its ability to activate and mature immature DCs into a sub-class of dendritic cells that elicit Type-1 immune responses.

The clinical studies with IMM-101 have so far been promising and IMM-101 showed efficacy signals in pancreatic cancer when combined with gemcitabine and in melanoma when given alone or as additional therapy. In a study published in 2016 by Prof Dalgleish, IMM-101 in a randomised phase 2 study in combination with gemcitabine showed improvement in the progression free survival and in the overall survival of metastatic pancreatic cancer patients compared to gemcitabine alone without additional toxicity. Dr Fusi presented in 2019 at the Society for Melanoma Research Meeting an update of the IMM-101-008 study which was a Phase 1 placebo controlled, dose escalation study of IMM-101 in patients with advanced stage III/stage IV melanoma. The final results showed significan extented survival of somem of the patients enroleld in this study

IMM-101-015 was a clinal trial aiming to investigate the safety and efficacy of IMM-101 in combination with nivolumab, both in treatment-naïve patients and in those patients whose disease has progressed during anti-PD-1 therapy. The study was performed at two UK centres (St George`s University Hospitals NHS Foundation Trust and The Christie Hospital NHS Foundation Trust) between 2018 and 2021.

All patients received one 1.0 mg (0.1 mL) dose of IMM 101 every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then every 2 weeks for the next 3 doses, and thereafter every 4 weeks. Nivolumab and Ipilumumab were prescribed according to standard practice.

Sixteen patients with advanced melanoma and evaluable lesions, were eligible for the study. Treatment naive patients received nivolumab and IMM-101 whereas patients not responsive to anti-PD1 had the option to receive ipilimumab plus IMM-101. The primary objectives of the study were to evaluate the overall response rate after a maximum of 18 months of treatment and to assess the safety of the combination of IMM-101 + with checkpoint blockades.

The response rate in treatment-naïve patients was 73% whereas all the patients pre-treated progressed on the investigational combination. The median progression-free survival time for treatment-naïve patients was about 10 months with 41% of the pts progression-free at 18 months. The combination was very well tolerated, there were no new toxicities or increased toxicity.

The results were very promising ansd would warrant further investigations in a randomised study. IMM-101 in combination with nivolumab was in fact deemed safe and showed encouraging antitumor activity in treatment-naive patients with advanced melanoma.

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