Phase 1 study of DK2 10 (EGFR), a tumor-targeted IL2 x IL10 dual immunocytokine, in advanced cancer patients: Dose escalation, immune activation, and safety results.
Year: 2025
Type: conference-abstract
Abstract: 2589 Background: IL-2 induces anti-tumor immunity and toxicity, predominantly vascular leak syndrome (VLS), leading to edema, hypotension, organ toxicity, and therapy-inhibiting regulatory T cell (Treg) accumulation. DK2 10 (EGFR) couples wild-type IL-2 to a high affinity variant of EBV IL-10 via an scFv that binds to epidermal growth factor receptors. The IL-10 component was designed to block IL-2 mediated cytokine release syndrome (CRS) and VLS while retaining T cell activation and proliferation and limiting Treg expansion. We report the clinical and pharmacodynamic results from the dose escalation in the DEKA-1 phase 1 (NCT05704985) study. Methods: Eligible patients (pts) had advanced/metastatic tumors known to express EGFR, progressive disease on ≥1 lines of systemic treatment, and ECOG ≤1. DK2 10 (EGFR) (2-16 mg; 0.025-0.5 mg/kg for an 80 kg subject) was self-administered subcutaneously 3 times per week in 21-day cycles following a BOIN design. Adverse events (AEs) including serious (SAEs) were evaluated using CTCAE version 5.0. Cytokines and anti-drug antibodies were monitored during the first cycle and every 3 cycles thereafter. RECIST 1.1 tumor responses were evaluated every 9 weeks. Results: 35 pts (14 RCC, 6 NSCLC, 9 CRC, 5 PDAC, 1 SCC) were enrolled. Median age was 63 yrs (range 35-80). Treatment-related AEs (TRAEs; any grade) in ≥ 10% pts were injection site reactions (63%), fever (40%), fatigue (31%), nausea (23%), anemia (17%), chills (17%), eosinophilia (14%), CRS (14%), diarrhea (11%); the majority were G1-2. G3 TRAEs included fatigue (n = 4), anemia (n = 3), syncope (n = 3) and single events of acute kidney injury, cellulitis, hypoalbuminemia, and lymphopenia. No DLTs were observed. While MTD was not exceeded, a dose proportional induction of IFNγ was observed through 8 mg but not at 16 mg. Therefore, higher doses were not explored, and a 12 mg dose level was introduced for dose optimization. No appreciable increase in IL-6, TNF-a, or IL-1β was seen other than 1 subject at 4 mg with G2 CRS and elevated IL-6. IFNγ and IL-5 were concomitantly induced proportional to dose level and reached saturation between levels 3 and 4, consistent with pK exposure of DK2 10 (EGFR). Sustained IL-5 associated eosinophilia was observed and correlated with drug concentration but did not require intervention. IL-2 and IL-10 induction led to sustained elevation of IL-2Ra and IL-18, respectively. 33% of evaluable patients had a best ORR of SD. Conclusions: DK210 (EGFR) demonstrates strong IL-2 activity shown by IL-5 driven eosinophilia, shed IL-2Ra, T and NK cell proliferation and expansion but not Treg accumulation. These effects have been decoupled from IL-2 driven toxicity, confirming the hypothesis of the balancing effect of IL-10. These data support further evaluation in combination with T cell engagers, T cell therapeutics, and kinase inhibitors. Clinical trial information: NCT05704985 .
Source: Journal of Clinical Oncology
Institutions: Deka Biosciences (United States), The University of Texas MD Anderson Cancer Center, The University of Texas Southwestern Medical Center, OU Health Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Northwell Health, City Of Hope National Medical Center, Mary Crowley Cancer Research Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410805129