605O - YL201, a novel B7H3-targeting antibody-drug conjugate (ADC), in patients (pts) with advanced solid tumors: Results from a first-in-human phase I study

Background

YL201 is a B7H3-targeting ADC with a tumor microenvironment activable linker and a novel topoisomerase I inhibitor payload. Here, we report safety and preliminary efficacy of YL201 monotherapy in pts with advanced solid tumors from phase 1 dose escalation and expansion study.

Methods

Pts with metastatic/locally advanced solid tumors with ECOG PS ≤1 were treated with YL201 intravenously Q3W. For dose escalation, the 3+3 design was utilized with six dose levels from 0.8 to 3.0 mg/kg. For dose expansion, pts with selected tumor types were treated at the recommended expansion doses (REDs).

Results

As of 26 Apr 2024, 276 pts were enrolled and received at least one dose (dose escalation, n=49; dose expansion, n=227). The top 3 tumor types enrolled were small cell lung cancer (SCLC, n=79), nasopharyngeal carcinoma (NPC, n=75), and non-small cell lung cancer without actionable genomic alterations (NSCLC without AGAs, n=44). 60% pts had previously received at least 2 lines of therapy. During dose escalation, DLTs were observed at 2.8 mg/kg (n=1) and 3.0 mg/kg (n=2) including neutropenia, febrile neutropenia and thrombocytopenia, and 2.0 and 2.4 mg/kg were selected as REDs in dose expansion. Among the response-evaluable pts treated at ≥2.0 mg/kg (n=146), the response rates were 73.7%, 45.9%, and 32.1% in pts with SCLC, NPC, and NSCLC without AGAs, respectively. The 3-month DoR rates were 77.5% and 91.7% in SCLC and NPC. The most common hematological TRAEs were leukopenia (52.9%; grade [G]≥3: 22.5%), anemia (51.1%; G≥3: 14.9%) and neutropenia (48.9%; G≥3: 23.9%), while decreased appetite (22.5%; G≥3: 1.1%) and nausea (21.0%; G≥3: 0.7%) were the most common non-hematological TRAEs. One (0.4%) interstitial lung disease was reported. The PK, updated DoR and other details will be presented in the meeting. Table: 605O

Conclusions

YL201 has demonstrated encouraging efficacy in heavily pretreated advanced solid tumors with manageable safety and tolerability profile.

Clinical trial identification

NCT05434234 & NCT06057922.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

MediLink Therapeutics (Suzhou) Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.