Immune checkpoint blockades or checkpoint inhibitors (CPIs) have emerged as a breakthrough for patients with metastatic melanoma and more recently they have been licensed for other tumour types. The combination of nivolumab and ipilimumab has shown high response rates (58% objective response with about 20% of complete responses) but this comes with significant toxicity.

IMM-101 is a suspension of heat-killed whole cell Mycobacterium obuense (M. obuense) sourced from the National Collection of Type Cultures (NCTC) which had shown clinical benefit in stage IV melanoma patients as single agent.

Before the IMM-101-015 trial, Prof. Dalgleish and Dr Fusi have reported on four cases who have received treatment with IMM-101 and a checkpoint blockade (either sequentially or as a combination) and had complete remission.

The most impressive case of the one of a 79-year-old male who presented in 2014 with a melanoma on his left cheek and with a positive nodes in the left neck surgically resected. A few months after the surgery, he paracardiac nodes, adrenal, lung and multiple large subcutaneous metastatic deposits. In view of his age and performance status he was commenced on IMM-101 on a named-patient program with initial stabilisation of disease. Upon rapid progression of the subcutaneous disease IMM-101 was stopped and started on pembrolizumab, which showed a very rapid benefit as the subcutaneous lesions started to shrink within 4 days of the first infusion. The other sites of disease also responded to treatment, and he achieved a complete response (complete remission) within a few months from commencing pembrolizumab.
Of note none of the patients described had significant toxicity from the sequential or combinatory treatment.

The Authors concluded that based on their experience with IMM-101 and checkpoint blockades, the use of IMM-101 in the 4 patients reported may have enhanced the effects of the checkpoint inhibitor resulting into the complete responses seen. IMM-101 may have activated in fact a complementary pathway which is synergistic with the checkpoint blockade treatment.
These observations led to a clinical trial to assess the safety and the efficacy of IMM-101 in combination with nivolumab in metastatic melanoma patients (IMM-101-015: results reported).