MediLink Presents YL201 at ESMO 2024: Over 6 Months PFS in SCLC, Pan-Tumor Benefits

MediLink Therapeutics has unveiled the inaugural clinical data for YL201, a novel B7H3-targeting antibody-drug conjugate (ADC), during an oral presentation at the European Society for Medical Oncology (ESMO) Congress 2024. This marks the first public disclosure of clinical results for YL201, developed utilizing MediLink's proprietary Tumor Microenvironment Activable LINker-payload (TMALIN®) platform.

The reported findings stem from Phase I studies (NCT05434234 & NCT06057922) conducted in China and the US, aimed at assessing the safety and efficacy of YL201 in advanced solid tumor patients. As of August 9, 2024, 312 patients had participated in the dose escalation and expansion trials, encompassing various cancer types such as small cell lung cancer (SCLC), nasopharyngeal carcinoma (NPC), and non-small cell lung cancer without actionable genomic alterations (NSCLC without AGAs). Notably, all patients had undergone prior standard therapy, with 60% having at least two previous treatment lines.

During the dose escalation phase, dose-limiting toxicities were recorded at 2.8 mg/kg (1 patient) and 3.0 mg/kg (2 patients). For the dose expansion phase, 2.0 mg/kg and 2.4 mg/kg were selected as the recommended doses. By August 9, 2024, 276 patients had undergone tumor assessments according to RECIST V1.1 criteria, revealing an overall response rate (ORR) of 44.6% and a disease control rate (DCR) of 83.7%. The median follow-up duration was 5.4 months, with 46% of patients still undergoing treatment.

YL201 demonstrated promising antitumor activity across multiple solid tumor types. Specifically, in extensive-stage SCLC patients, 72 of whom had evaluable tumor assessments and prior platinum-based chemotherapy and anti-PD-(L)1 treatments, the ORR was 68.1%, with a median progression-free survival (mPFS) of 6.2 months. Additionally, for patients with brain metastasis, the ORR was 52.2% and the mPFS was 5.3 months, comparable to the overall population.

In 70 NPC patients with evaluable tumor assessments, the ORR was 48.6%, and the mPFS was 7.2 months. Heavily treated NPC patients with at least two prior treatment lines exhibited similar efficacy, with an ORR of 51.0% and mPFS of 7.0 months.

For NSCLC without AGAs, all patients had prior treatments with anti-PD-(L)1 and platinum-based chemotherapy. Among adenocarcinoma and LELC histological subtypes, ORRs were 29.2% and 60.9%, respectively, while mPFS remained unmatured for adenocarcinoma but was 8.1 months for LELC.

The safety profile of YL201 indicated that grade 3 and higher treatment-related adverse events (TRAEs) occurred in 51% of patients, with serious TRAEs in 28%. The most frequent hematological TRAEs were leukopenia (29%), anemia (22%), and neutropenia (30%), while the most common non-hematological TRAEs included decreased appetite and nausea (both 1%). Only 1% of patients reported treatment-related interstitial lung disease.

Dr. Steve Chin, Chief Medical Officer of MediLink, expressed enthusiasm over the results presented at the ESMO Congress, highlighting the significant improvement in antitumor activity for YL201 compared to historical data for standard treatments. The drug was well tolerated, with the most common adverse events being manageable hematological toxicities. MediLink is actively preparing for Phase 3 studies of YL201 in various cancer types, including SCLC and NPC.

YL201 is an innovative ADC targeting B7-H3, a protein overexpressed in many malignant cells but limited in normal tissues, making it a promising therapeutic candidate. Developed through MediLink's TMALIN® platform, YL201 is currently under investigation in several Phase I and II studies, including a multi-national Phase I clinical trial.