Treatment With SOT101 and Pembrolizumab Commences in Phase 2 AURELIO-04 Study

: On the heels of positive findings from the phase 1/1b AURELIO-03, 1 patient with an advanced/refractory solid tumor has been dosed with SOT101 and pembrolizumab in the follow-up study, AURELIO-04.

The first of approximately 320 patients with advanced/refractory solid tumors has been dosed with the combination of SOT101(previously SO-C101) and pembrolizumab (Keytruda) in the phase 2 AURELIO-04 study (NCT05256381), according to a press release issued by SOTIO Biotech.1

SOT101 is an interleukin (IL)-15 superagonist that had demonstrated preclinical efficacy in various tumor models. Specifically, the agent prolonged survival and improved tumor regression in in vivo models. The agent also demonstrated a favorable toxicity profile preclinically.

“The continued clinical development of SOT101 is crucial as we still face a significant need to provide more effective therapeutic options for patients with solid tumors. Validated by promising phase 1/1b AURELIO-03 data, AURELIO-04 will aim to confirm safety and demonstrate efficacy of SOT101 in combination with pembrolizumab in additional indications,” said Stéphane Champiat, MD, PhD, head of the Inpatient Unit at the Drug Development of Gustave Roussy Cancer Center and coordinating investigator of AURELIO-04, in a press release.

In the previous study, AURELIO-03 (NCT05256381), treatment with SOT101 in combination with pembrolizumab achieved a complete response in 1 of 16 heavily pretreated patients, and partial responses were observed in 4 patients. Five patients in the study had confirmed stable disease of at least 50 weeks. Moreover, 12 of the patients derived clinical benefit from SOT101/pembrolizumab. Based on the AURELIO-03 results, AURELIO-04 was conducted to further evaluate the efficacy and safety of the combination.2

In the open-label, single-arm multicenter AURELIO-04 study, investigators will evaluate the efficacy and safety of SOT101 and pembrolizumab in patients with selected advanced/refractory solid tumors.

The study’s primary end point is objective response rate (ORR) according to RECIST v1.1 criteria. The secondary end points of the study include the number of patients with treatment-emergent adverse events, the number of patients with adverse events (AEs) of special interest, best overall response, immune best overall response, duration of response (DOR), immune DOR, clinical benefit rate, progression-free survival (PFS), immune PFS, time to response (TTR), and immune TTR.3

In the metastatic castration-resistant prostate cancer (mCRPC) cohort, investigators will also assess clinical benefit rate and PFS according to PCWG3-modified RECIST 1.1, circulating tumor cell count conversion, confirmed prostate-specific antigen decline of ≥ 50%, and the time to confirmed prostate-specific antigen progression according to PCWG3-modified RECIST 1.1, as well as SOT101 plasma concentration profile at timepoints, and the number of patients with anti-drug antibodies.

Patients are eligible to enroll in AURELIO-04 if they have histologically or cytologically confirmed sold tumors including non–small cell lung cancer (NSCLC), colorectal cancer, cutaneous squamous cell carcinoma, advanced hepatocellular carcinoma, mCRPC, and ovarian cancer. All patients are required to have measurable disease per RECIST 1.1, accessible tumor tissue, an ECOG performance status of 0-1, adequate organ, renal, and hepatic function, and be using adequate contraception. Patients must have also recovered from all AEs caused by previous therapies to grade 1 or lower.

The study excluded individuals who have been previously treated with an anti-PD-1, anti-PD-L1, or anti-PD-L2 inhibitor. In addition, patients treated with an IL-2 or IL-15 agent, systemic anti-cancer therapy, radiotherapy within 2 weeks of the study, allogeneic hematopoietic stem cell transplantation within the last 5 years, or prior allogeneic tissue/solid organ transplantare ineligible for enrollment. Patients with NSCLC who received radiation therapy to the lung > 30 Gy within 6 months are also ineligible for the study. The study also excludes patients with certain comorbidities that may impact treatment outcomes.

“The initiation of this phase 2 study is a significant milestone for the clinical development of SOT101,” said Richard Sachse, MD, PhD, chief medical officer of SOTIO and managing director of SOTIO Biotech in Switzerland, in the press release.1 “IL-15 has been widely favored as a promising cytokine in oncology, but IL-15-based approaches to date have fallen short of realizing this promise due to aberrant targeting and adverse events. SOT101 in combination with Keytruda has shown encouraging early clinical efficacy in the AURELIO-03 phase 1 study and we look forward to building upon our findings to advance this innovative therapy for the potential benefit of patients battling cancer.”


1. SOTIO doses first patient in AURELIO-04 phase 2 trial of SOT101 in combination with keytruda® (pembrolizumab). News release. SOTIO Biotech. July 26, 2022. Accessed July 26, 2022.

2. Champiat S, Marabelle A, Galvao V, et al. SOT101, an IL-2/IL-15 Rβγ superagonist, in combination with pembrolizumab in patients with advanced solid tumors: Interim safety and efficacy results from the AURELIO-03 dose escalation trial. Presented at: American Association for Cancer Research Annual Meeting 2022; April 8-13, 2022; New Orleans, LA. Abstract CT040.

3. A study of SOT101 in combination with pembrolizumab to evaluate the efficacy and safety in patients with selected advanced solid tumors. Updated July 26, 2022. Accessed July 26, 2022.