“Molecular Glue Degrader Improves Outcomes in Heavily Pre-treated Patients with Advanced Solid Tumors”
An interview with:
Elena Garralda MD PhD, Medical Oncologist, Head, Early Drug Development Unit, Vall d’Hebron Hospital, Barcelona, Spain
SAN DIEGO, USA—Cancer cell transcription lies at the heart of a new therapy that has demonstrated potential for treating solid tumors that have become refractory to standard therapy. New data were reported, at the 2026 Annual Meeting of the American Association for Cancer Research, by a group from Spain on the use of a so-called “molecular glue degrader” that modulates transcription to treat cancer. First author Elena Garralda MD PhD, a medical oncologist who leads the Early Drug Development Unit at Vall d’Hebron Hospital in Barcelona, talked about her findings with Peter Goodwin:
AUDIO JOURNAL OF ONCOLOGY: Elena Garralda MD PhD
IN: [GOODWIN] “I am in San Diego at the ….
OUT: ..Audio Journal of Oncoloty, I’m Peter Goodwin” 8:38 secs
2026 AACR Abstract Title
CT006 – “Phase 1 DKY709A12101C study in patients with advanced solid tumors treated with DKY709, an IKZF2 degrader, alone or in combination with PDR001, a PD-1 inhibitor”
Presenter/Authors
- Garralda1, C.-C. Lin2, T. Koyama3, B. Ma4, M. Johnson5, M. Schuler6, M. Wermke7, J. Gainor8, R. Gopal9, D. Long9, J. Kim9, D. Maddirala10, A. Dang9, X. Yang9, M. Awad11;
1VHIO Vall D’Hebron Institute of Oncology, Barcelona, Spain, 2National Taiwan University Hospital, Taipei, Taiwan, 3National Cancer Center Central Hospital, Tokyo, Japan, 4Prince of Wales Hospital, Shatin, Hong Kong, China, 5Sarah Cannon Research Institute, Nashville, TN, 6University Hospital Essen, Essen, Germany, 7Dresden University of Technology, Dresden, Germany, 8Massachusetts General Hospital, Boston, MA, 9Novartis Pharmaceuticals Corporation, East Hanover, NJ, 10Novartis India Limited, Boston, MA, 11Dana-Farber Cancer Institute, Boston, MA
Background:
DKY709 is an orally administered molecular glue degrader of IKZF2, a transcription factor expressed in regulatory T cells. PDR001 (spartalizumab) is a humanized monoclonal antibody directed against programmed cell death 1 protein (PD-1). This phase 1 study was designed to assess the safety, pharmacokinetics, and preliminary efficacy of DKY709 as monotherapy or in combination with PDR001 in patients with advanced solid cancers.
Methods:
DKY709A12101C (NCT03891953) was a global, phase 1, open-label study in patients with advanced cancers, including non-small cell lung cancer (NSCLC) and melanoma previously treated with anti-PD-1/PD-L1 therapy, or previously treated nasopharyngeal carcinoma (NPC). Patients received DKY709 alone (arm A) or in combination (arm B) with PDR001 (400 mg Q4W or 300 mg Q3W intravenously). During dose escalation, 20 mg was the starting dose and patients also received 4, 6, 10, or 40 mg (arm A only) of DKY709 by mouth QD continuously. An intermittent dosing schedule for DKY709 (20 or 10 mg) of either 3 or 2 weeks on followed by 1 week off was implemented in both arms. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics, pharmacodynamics, and preliminary antitumor activity.
Results:
At data cutoff (Sep 5, 2024), 58 patients were treated with DKY709 (30 with melanoma, 4 with NPC, and 24 with NSCLC) and 40 with DKY709 + PDR001 (12 with melanoma, 13 with NPC, and 15 with NSCLC). Median age was 60 years; 46% of participants were female. DKY709 showed dose-proportional exposure with 2- to 3-fold accumulation and achieved IKZF2 degradation of ≥90% in peripheral regulatory T cells with all doses ≥6 mg. Dose-limiting toxicities occurred in 3 patients receiving monotherapy and 2 receiving the combination. The most common treatment-related adverse events were myalgia (17.2%) with DKY709 monotherapy and AST/ALT increase (22.5%) and diarrhea (22.5%) with DKY709 + PDR001. Reversible peripheral neuropathy related to DKY709 was observed in 28% and 30% of patients receiving monotherapy and the combination, respectively; lower doses and intermittent schedules were associated with less neurotoxicity. The disease control rate in the monotherapy arm was 44.8% and included 1 confirmed complete response (melanoma) and 3 confirmed partial responses (2 melanoma and 1 NSCLC). The disease control rate in the combination arm was 37.5% and included confirmed partial responses in 5 patients (2 melanoma, 2 NPC, and 1 NSCLC). The recommended dose for expansion was 6 mg QD continuously in the monotherapy and combination arms.
Conclusions:
DKY709 achieved IKZF2 degradation of ≥90% in peripheral regulatory T cells at doses ≥6 mg. DKY709 as monotherapy and in combination with anti-PD-1 therapy reduced tumor volume in patients with NPC and those with NSCLC and melanoma previously treated with immunotherapy.
Elena Garralda AACR 2026 Audio Journal of Oncology Text April 23, 2026
