“The new results highlight the potential of nadunolimab as a cancer therapy providing both antitumor effects while, at the same time, reducing neuropathic side effects when combined with chemotherapy. This finding may also be of relevance in other neuroinflammatory conditions,” said Göran Forsberg, CEO of
Neuropathy is a serious medical condition and a side effect of several classes of chemotherapies. The main symptoms are weakness, pain and numbness in hands and feet. Neuropathy often leads to discontinuation of therapy in patients despite effective antitumor activity. The mechanisms behind chemotherapy induced neuropathy relate to damaged nerve cells and neuroinflammation, where the IL-1 pathway has been indicated as a key driver. With nadunolimab blocking IL-1 activity through its binding to IL1RAP, nadunolimab has the potential to counteract neuropathy during treatment with chemotherapies, such as paclitaxel.
In the CANFOUR trial, 73 first line pancreatic cancer patients were treated with nadunolimab and gemcitabine/nab-paclitaxel. The median survival of 13.2 months and iPFS of 7.2 months are longer than expected from historical control data for the chemotherapy alone (1). The incidence of neuropathy was notably lower than expected from chemotherapy treatment. Only one grade 3 event was observed and a statistically significant (p=0.042) relationship between dose level and any grade neuropathy was observed. At 1 mg/kg nadunolimab, 60% of patients had any grade neuropathy with a median time to onset of 112 days. At 2.5 mg/kg or higher, only 36% had any grade neuropathy and median time to onset was not reached.
Studies in mouse models show that several aspects of chemotherapy induced neuropathy, such as sensitivity to mechanical pressure, temperature and decreased grip strength, all were prevented by concomitant treatment with the nadunolimab surrogate antibody. Combination studies were performed with either paclitaxel or vincristine.
The preclinical data were generated in collaboration with Hana Starobova and colleagues at University of
Reference
1) OS 8.5 mo, PFS 5.3 mo, (Von Hoff et al, N Engl J Med 2013); OS 9.2 mo, PFS 5.6 mo, (Wainberg et al,
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