KEY TAKEAWAYS
- The phase 1 study in advanced solid tumors assessed the safety and dosage of a novel therapy administered bi-weekly and weekly.
- The main goal was to evaluate how safe and well-tolerated SAR445710 was as a standalone treatment.
- SAR445710 showed a manageable toxicity profile and displayed expected pharmacological actions linked to IL-15 activation.
Extensive in vitro and in vivo studies showed SAR445710 and its mouse cross-reactive surrogate to have substantial efficacy and therapeutic advantages over IL-15 alone. The approach of SAR445710 potentially exploits PD-L1 targeting to transport IL-15 into the tumor microenvironment.
The study, registered as NCT04242147, was a phase 1 trial conducted across multiple centers, focusing on patients with locally advanced or metastatic solid tumors.
Using a ‘3+3’ design for dose escalation, the study evaluated dose-limiting toxicity (DLT) within the initial 28 days. Different dosing schedules – bi-weekly (Q2W) and weekly (QW) – were tested, ranging from 3–400 μg/kg (Q2W) and 50–300 μg/kg (QW). The main goal was to evaluate how safe and well-tolerated SAR445710 was as a standalone treatment.
As of July 31, 2023, 39 patients (median age: 61.5 years; 46.15% females) underwent dose escalation – 27 on a bi-weekly (Q2W) schedule and 12 on a weekly (QW) schedule. In the Q2W dosing, three dose-limiting toxicities (DLTs) occurred: two Grade 3 cytokine release syndromes at 400 μg/kg and one Grade 3 pneumonitis at 200 μg/kg. No dose-limiting toxicities (DLTs) were observed in the weekly (QW) schedule.
The maximum tolerated dose (MTD) for Q2W was 200 μg/kg. Common treatment-related adverse events included pyrexia (57.1%) and chills (42.9%), mostly resolving with supportive care. Most patients achieved stable disease as the best overall response.
SAR445710 demonstrated anticipated effects on immune responses, promoting NK and CD8 T cell expansion. Pharmacokinetics showed a non-linear profile in the Q2W schedule from 3–400 µg/kg, as expected for targeted antibodies. Enrollment is ongoing for the QW schedule. SAR445710 showed controllable side effects and exhibited pharmacodynamics aligned with IL-15 stimulation.
Source: https://jitc.bmj.com/content/11/Suppl_2/A1774
Clinical Trial: https://clinicaltrials.gov/study/NCT04242147
Luke J, Olszanski AJ, Rosen L, et al782-I Phase I dose escalation of SAR445710, a PDL1-IL15 targeted cytokine in metastatic and/or advanced solid tumorsJournal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0782-I
