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.
Elena Garralda, Aung Naing, Vladimir Galvao, Patricia LoRusso, Peter Grell, Philippe A. Cassier, Carlos Gomez‐Roca, Iphigénie Korakis, David Béchard, Lenka Palová Jelínková, Irena Adkins, Sascha Tillmanns, Joachim Kiemle-Kallee, Aurélien Marabelle, Stéphane Champiat
Abstract
2502 Background: SOT101 (previously SO-C101) is a fusion protein of IL-15 and the IL-15 receptor α sushi+ domain. Synergistic effects of SOT101 and an anti-programmed cell death protein 1 antibody have been validated in various tumor mouse models inducing a protective memory response. Methods: In this phase 1 study, safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of increasing doses of SOT101 administered subcutaneously were investigated in patients (pts) with advanced solid tumors as monotherapy (Part A) and in combination with pembrolizumab every 3-week cycle (Part B). Dose escalation followed a standard 3+3 design. Data cut-off was 26 January 2022. Results: Overall, 51 pts were treated: 30 in Part A monotherapy at 0.25 to 15 μg/kg SOT101 and 21 in Part B combination therapy (Tx) at 1.5 to 12 μg/kg SOT101. The median (range) number of previous lines of Tx was 3 (1-9) in Part A and 2 (1-6) in Part B. In Part A, 19 (63.3%) pts had previous check-point inhibitor (CPI) Tx, of whom 9 (30 %) were refractory, 5 (16.7%) relapsed. In Part B, 11 pts (52.4%) had previous CPI Tx, and the outcome was 9 (42.9%) pts relapsed, 1 (4.8%) refractory. The most common treatment-emergent adverse events (TEAEs) were transient, and included pyrexia, chills, lymphopenia, anemia, transaminase elevation and vomiting. Most TEAEs were ≤ Grade 2. No treatment-related death was reported. For both monotherapy and combination Tx, the recommended phase 2 dose of SOT101 was determined to be 12 μg/kg. In Part A, in 13 pts at 6 to 12 μg/kg SOT101, the observed clinical benefit rate was 38%. A partial response (PR) was confirmed in 1 pt with skin squamous cell carcinoma, CPI refractory, PR duration 46 days (d), on treatment 154 d. Four pts (all CPI pretreated) had stable disease (SD), range 33-183 d. Final median duration on treatment was 84 d, range 43-183 d. The median duration of clinical benefit was 190 d. In Part B, the observed clinical benefit rate across all SOT101 doses was 63%. A complete response (CR) was confirmed in 1 pt with mesothelioma, CPI naïve, starting at the first tumor assessment, and the pt is ongoing in cycle 5. Three pts, 2 CPI pretreated, had a PR, range 51-232 d, 2 ongoing with PR, and 1 Tx discontinuation while still on PR. Five pts, 3 CPI pretreated, had SD, range 92-340 d, 2 ongoing with SD. The 3 CPI pretreated pts had SD range 41-340 d, 1 pt ongoing. The preliminary median duration on combination Tx was 113 d, range 7-429 d. The preliminary median duration of clinical benefit was 131 d. Conclusions: SOT101 as monotherapy and in combination with pembrolizumab showed a favorable safety profile. Highly promising efficacy signals with one ongoing CR and several long-lasting PRs were reported in CPI-naïve and CPI pretreated pts, including CPI-resistant tumors. Clinical trial information: NCT04234113.