FDA Type C Meeting Supports Phase 3 Design for DLL3-Targeted ADC in ES-SCLC

A type C meeting between IDEAYA Biosciences and the FDA has established the design of a phase 3 registrational trial for IDE849, a delta-like ligand 3 (DLL3)–targeting antibody-drug conjugate, in patients with extensive-stage small cell lung cancer (ES-SCLC).¹

The planned global registrational study, anticipated to begin by the end of 2026, will enroll approximately 400 patients with ES-SCLC who have previously received tarlatamab (Imdelltra). Patients will be randomized 1:1 to IDE849 monotherapy or a control arm to receive investigator's choice of chemotherapy consisting of either topotecan or amrubicin.

"Based on the FDA type C meeting, we are targeting to initiate a randomized [p]hase 3 registrational study for IDE849 monotherapy in extensive stage [SCLC] to enable a potential accelerated approval and full approval in one seamless study design," Yujiro S. Hata, president and CEO of IDEAYA Biosciences, stated in a news release.¹

To support potential accelerated approval, the primary end point of the trial will be overall response rate as assessed by blinded independent central review (BICR), while median overall survival will serve as the primary end point for full approval. Secondary end points will include median duration of response by BICR, progression-free survival, and safety.

Mechanistic Rationale for DLL3 Targeting

DLL3 is upregulated across several solid tumor types, including SCLC, neuroendocrine carcinoma, and melanoma, making it a therapeutic target of interest. IDE849, consisting of an anti-DLL3 IgG1 monoclonal antibody carrying a topoisomerase I payload, is designed to selectively deliver cytotoxic activity to DLL3-expressing tumor cells.

Clinical Development: Phase 1 Trial

Dose selection for the phase 3 study is being informed by an ongoing multisite, global phase 1 trial evaluating IDE849 as monotherapy and combination therapy in patients with DLL3-upregulated solid tumors, including SCLC and neuroendocrine carcinoma (NCT07174583).² The trial has been underway since the fourth quarter of 2025, a few months following FDA clearance of IDE849’s investigational new drug (IND) application in May 2025. Investigators are now evaluating expansion doses of 2.4 mg/kg and 3.5 mg/kg administered intravenously once every 3 weeks to determine the recommended phase 3 dose.

IDE849 is also being evaluated in combination with durvalumab (Imfinzi), a PD-L1 inhibitor, and IDE161, IDEAYA's investigational PARG inhibitor, in a study intended to inform a potential phase 3 registrational design in the first-line SCLC setting.

In interim data presented during the 2025 World Conference on Lung Cancer, IDE849 demonstrated manageable safety and preliminary antitumor activity in patients with relapsed SCLC.³ Additional clinical data for IDE849 in a combined total of 100 patients with ES-SCLC are expected at the European Society for Medical Oncology (ESMO) 2026 Congress.

REFERENCES

1. IDEAYA Biosciences Announces Successful FDA Type C Meeting for IDE849, DLL3 TOP1 ADC, on Phase 3 Registrational Trial Design for Potential Accelerated and Full Approval in Extensive Stage Small Cell Lung Cancer. News release. IDEAYA Biosciences. August 31, 2026. Accessed August 31, 2026. https://tinyurl.com/yck7cvhv

2. A Study of IDE849 in Patients With DLL3 Expressing Tumors Including Small Cell Lung Cancer. ClinicalTrials.gov. Updated July 9, 2026. Accessed August 31, 2026. https://clinicaltrials.gov/study/NCT07174583

3. Cheng Y, Meng X, Zhang Y, et al. A first-in-human phase 1 study of SHR-4849 (IDE849), a DLL3-directed antibody-drug conjugate, in relapsed SCLC. J Thorac Oncol. 2025;20(10 suppl 1):S21.