Background IL-15 is a member of the common y-chain family of cytokines that shares functional activities with IL-2. SO-C101is a superagonist fusion protein of IL-15 and the IL-15 receptor α sushi+ domain. SO-C101 stimulates the proliferation and the cytotoxic activity of NK cells and memory CD8+ T cells.

In pre-clinical studies SO-C101 promoted expansion and activation of human, murine and cynomolgus monkey NK and CD8+ T cells. NK and CD8+ T cell activation correlated with potent monotherapy anti-cancer activity of SO-C101 in metastatic and solid tumor models. The combination of an anti-PD-1 or of anti-cancer monoclonal antibodies with SO-C 101 augmented the anti-tumor responses in mouse models. First clinical study was initiated in June 2019 to investigate SO-C101 as monotherapy and in combination with pembrolizumab.

Methods The phase 1/1 b study currently on-going is a multicenter, open-label, dose escalation study for patients with selected advanced/metastatic solid tumors. The study consists of 2 parts: Part A - dose escalation of SO-C101 as monotherapy; Part B - dose escalation of SO-C101 in combination with pembrolizumab. Study objectives are to define the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of SO-C101 in both parts.

Results As of September 22nd, 19 subjects were treated in part A in 6 escalating dose levels, and 3 subjects were treated in part B, at dose level 1.

SO-C101 was well tolerated. No DLT was observed, the main AEs related to SO-C101 were injection site reactions, fever, chills, flu-like syndrome, all G1- G2, and transient lymphopenia in 5 subjects, Grade 2 to 4, all resolved within few days.

Preliminary PK results showed the PK profile to be dose-proportional, with a Tmax of approx. 5 – 6 hours after administration and T½ approx. 4 hours.

Preliminary PD analysis showed dose dependent NK and CD8+ T cell activation.

A preliminary efficacy signal has been observed in a patient refractory to anti-PD1 therapy, who showed a RECIST PR with initial 20% shrinkage of target lesions at 6 weeks and 49% shrinkage at 12 weeks on CT-scans.

Conclusions To date, SO-C101 has been well tolerated, with a manageable toxicity and encouraging signs of clinical activity. The study will proceed to reach a RP2D in both monotherapy and combination with Pembrolizumab. Expansion of the study in selected indications is warranted.

Trial Registration https://clinicaltrials.gov/ct2/show/NCT04234113?term=sotio&draw=3&rank=12

The study was approved to proceed by FDA – IND 140011 -and by the sites ECs.

Ethics Approval The NCT04234113 clinical trial was approved by each investigational site health agency and ethical committee.

Consent Written informed consent of patients was obtained prior enrollment in the NCT04234113 clinical trial.