Early results of an investigational HER3-targeting antibody-drug conjugate (ADC) showed anti-tumor activity across several subgroups of pretreated patients with non-small cell lung cancer (NSCLC).

Heavily pretreated patients with epidermal growth factor receptor-mutated (EGFRm) NSCLC — the largest cohort — had a confirmed overall response rate of 27.3% with 2.0 mg/kg of YL202/BNT326, a dose that is moving forward for further study. Confirmed overall response rates with a dose of 2.0 mg/kg were 9.1% in previously treated patients with squamous disease and 46.7% in previously treated patients with nonsquamous NSCLC without actionable genomic alterations.

“In nonsquamous patients without actionable genomic alterations, where HER3 ADC data are limited, our results show encouraging response rates after standard-of-care therapies,” said lead author Haifeng Liu, MD, while presenting the results at European Lung Cancer Congress (ELCC) 2026 in Copenhagen, Denmark.

The study included three cohorts:

(A2) Patients with NSCLC with EGFRm with a median of three prior lines of treatment that included a TKI and platinum-based chemotherapy (PBC) (n = 102) at doses of 2.0 mg/kg, 2.5 mg/kg, and 3.0 mg/kg given every 3 weeks.

(E1) Patients with squamous NSCLC who had received a median of one prior treatment lines — with or without PBC (n = 23) at 2.0 mg/kg given every 3 weeks.

(E2) Patients with nonsquamous, actionable genomic alteration-negative NSCLC who had received a median of two prior treatment lines, one of which had to include a PD-1 or a PD-L1 with or without chemotherapy (n = 27) at doses of 2.0 mg/kg, 2.5 mg/kg, and 3.0 mg/kg given every 3 weeks.

The co-primary endpoints were confirmed overall response rates and the selection of the recommended dose of YL202/BNT326 for further study. Secondary endpoints included progression-free survival and safety.

“This represents the first data presentation of a HER3-targeted ADC in patients with squamous NSCLC, addressing an important unmet need.” said Liu, who is a medical oncologist at Jilin Cancer Hospital in Changchun, China.

The median progression-free survival was 5.5 months for the group.

Discussant Kersti Oselin, MD, PhD, a thoracic oncologist at the Clinic of Oncology and Hematology at North Estonia Medical Centre, in Tallinn, Estonia, noted that “YL202/BNT326 HER3-ADC demonstrated encouraging antitumor activity in patients with EGFRm and prior TKI plus PBC treatment.” For these patients, the median progression-free survival was greater than 8.2 months at 2.0 mg/kg, a dose moved forward into phase 3, she said.

Adverse Events (AEs)

There were low treatment-discontinuation rates with YL202/BNT326, particularly with 2.0 mg/kg and 2.5 mg/kg dose levels, Liu said.

Grade 3-5 treatment-related AEs (TRAEs) occurred in 30.6%, 48.6%, and 55.8% across cohorts at doses of 2.0 mg/kg, 2.5 mg/kg, and 3.0 mg/kg, respectively. Treatment discontinuation occurred with three, one, and four patients across groups at doses of 2.0 mg/kg, 2.5 mg/kg, and 3.0 mg/kg, respectively. There was one TRAE leading to death in a patient who received 2.0 mg/kg YL202/BNT326.

Liu reported having no significant relationships related to the presentation. Oselin reported having significant relationships with several pharmaceutical companies.