SOT101 With or Without Pembrolizumab Achieves Antitumor Response in Advanced Solid Tumors

Encouraging efficacy signals in heavily pretreated patients with advanced solid tumor has been demonstrated in AURELIO-03 trial, and will be further evaluated in AURELIO-304.

In the phase 1 AURELIO-03 trial (NCT04234113) of SOT101 (previously SO-C101) alone and in combination with pembrolizumab (Keytruda), patients with advanced solid tumors had favorable safety outcomes with no added toxicity and promising efficacy was demonstrated with treatment, according to findings presented during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.1

“Encouraging efficacy signals were observed for the monotherapy and the combination even checkpoint inhibitor–relapsed tumors,” lead study author, Elena Garralda, head, Early Drug Development Unit, Vall Hebron Institute of Oncology, said in a presentation of the data.

SOT101 is a fusion protein of IL-15 and the IL-15 receptor α sushi+ domain. SOT101 and anti–PD-1 therapy have shown synergistic activity in tumor mouse models causing a protective memory response.

The phase 1 study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and early efficacy of step-up doses of subcutaneous SOT101 on days 1, 2, 8, and 9 in patients with advanced and metastatic solid tumors as a single agent (n = 30; part A) and in combination with 200 mg of intravenous pembrolizumab every 3 weeks until disease progression or unacceptable toxicity (n = 21; part B). In part A, patients were allowed to crossover to the combination arm following disease progression.

To be eligible for enrollment, patients also had to have an ECOG performance status of 0 or 1, measurable disease per iRECIST, adequate organ function, and no prior treatment with IL-2 or IL-15 like agonists. Prior treatment with checkpoint inhibitors was permitted.

Dose escalation followed a standard 3 + 3 design. The data cut-off was January 26, 2022.

In part A, patients received SOT101 monotherapy at a dose of 0.25 to 15 μg/kg. In part B, patients received SOT101 in combination with pembrolizumab at a dose of 1.5 to 12 μg/kg.

The median number of prior lines of therapy was 3 (range, 1-9) in part A and 2 (range, 1-6) in part B. In part A, 19 (63.3%) patients had received a prior checkpoint inhibitor, of whom 9 (30 %) were refractory and 5 (16.7%) had relapsed. In part B, 12 patients (57.1%) had received a prior checkpoint inhibitor to which 9 (42.9%) patients relapsed and 1 (4.8%) was refractory.

The most common treatment-emergent adverse effects (TEAEs) were short lived, and included pyrexia, chills, lymphopenia, anemia, transaminase elevation and vomiting. Most TEAEs were grade 2 or lower. No treatment-related death was reported.

The recommended phase 2 dose of SOT101 as a single agent and in combination with pembrolizumab was determined to be 12 μg/kg. In part A, the clinical benefit rate was 38% (n = 13) with doses ranging from 6 to 12 μg/kg.

A partial response (PR) was confirmed in 1 patient with checkpoint inhibitor–refractory, skin squamous cell carcinoma; the PR duration was 46 days, and the patient was on treatment for 154 days. ­Four patients, all of whom had received a prior checkpoint inhibitor had stable disease (SD; range, 33-183 days).

The final median duration on treatment was 84 days (range, 43-183), and the median duration of clinical benefit was 190 days.

In part B, the observed clinical benefit rate across all SOT101 doses was 63%. A complete response (CR) was confirmed in 1 patient with checkpoint inhibitor–naïve mesothelioma starting at the first tumor assessment, and the patient is ongoing in cycle 5. Three patients, 2 of whom had received a prior checkpoint inhibitor had a PR (range, 51-232 days). Two of the patients are in ongoing PR, and 1 patient discontinued treatment while still in PR.

Five patients, 3 of whom had received a prior checkpoint inhibitor had SD (range, 92-340 days); 2 patients have ongoing SD. The 3 patients who had received a prior checkpoint inhibitor had an SD range of 41 to 340 days; 1 patient remains in ongoing SD. The preliminary median duration on the combination therapy was 113 days (range, 7-429), and the preliminary median duration of clinical benefit was 131 days.

Additionally, the pharmacokinetic profile for SOT101 was similar for the monotherapy and combination regimen. Notably, SOT101 promoted proliferation of target immune cells without T regulatory cell proliferation in line with the anticipated mechanism of action.

Furthermore, all patients with best clinical response of PR or at least 2 instances of SD with SOT101 treatment showed increased tumor infiltrating lymphocyte density in tumors after treatment.

Increased immune cell density was also seen in the tumor tissue of patients with PR or confirmed SD with combination.

“This preliminary efficacy of the recommended phase 2 dose is currently being evaluated in expansion cohorts in skin squamous cell carcinoma, melanoma, and renal cell cancer. These encouraging efficacy signals in this heavily pretreated population will be further evaluated in the AURELIO-304 study [NCT05256381],” Garralda concluded.


Garralda E, Naing A, Galvao V, et al. Interim safety and efficacy results from AURELIO-03: a phase 1 dose escalation study of the IL-2/IL-15 receptor βγ superagonist SOT101 as a single agent and in combination with pembrolizumab in patients with advanced solid tumors. J Clin Oncol. 2022;40(suppl 16):2502. doi:10.1200/JCO.2022.40.116_suppl.2502