On September 13, 2024 MediLink Therapeutics (MediLink) reported clinical data for YL201, a novel B7H3-targeting antibody drug conjugate (ADC) developed based on MediLink’s Tumor Microenvironment Activable LINker-payload (TMALIN) platform, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Suzhou Medilink Therapeutics, SEP 13, 2024, View Source [SID1234646573]). This is the first disclosure of clinical data for YL201 featured in an oral presentation.

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Presented results are from phase I studies (NCT05434234 & NCT06057922) conducted in China and the US to explore the safety and efficacy of YL201 in patients with advanced solid tumors. As shown in the abstract, by August 9 2024, a total of 312 patients were enrolled in the dose escalation and expansion studies with various tumor types, including 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=68). All enrolled patients have been treated with prior standard therapy, and 60% had at least 2 prior treatment lines.

During dose escalation stage, dose limiting toxicities were observed at 2.8 mg/kg (n=1) and 3.0 mg/kg (n=2). For dose expansion, 2.0 mg/kg and 2.4 mg/kg were selected as recommended expansion doses. As of 09 Aug 2024, 276 patients had at least one post-baseline tumor assessment per RECIST V1.1., The overall response rate (ORR) was 44.6%, the disease control rate (DCR) was 83.7%. The median follow-up duration was 5.4 months, and 46% of the patients are still on treatment.

Antitumor activity was observed in multiple solid tumor types. In extensive-stage SCLC patients, among 72 patients who had evaluable tumor assessment, all patients had prior treatment with platinum-based chemotherapy, and 95% had prior treatment with anti-PD-(L)1. The ORR was 68.1% (at dose levels >= 2.0 mg/kg: 70.0%) and the median progress-free survival (mPFS) was 6.2 months (at dose levels >= 2.0 mg/kg: 6.2 months). Also worth mentioning was that in patients with brain metastasis, the ORR was 52.2% and mPFS was 5.3 months, comparable to those of overall population.

In 70 NPC patients with evaluable tumor assessment, the ORR was 48.6% (at dose levels >= 2.0 mg/kg: 48.6%), and mPFS was 7.2 months (at dose levels >= 2.0 mg/kg: 7.2 months). In heavily-treated NPC patients receiving at least 2 prior lines of treatment, the efficacy was also comparable, with ORR of 51.0% and mPFS of 7.0 months.

In NSCLC without AGA, all patients had prior treatment with anti-PD-(L)1 and platinum-based chemotherapy. In the histological subtypes of adenocarcinoma and LELC, ORR were 29.2% and 60.9%, respectively, and mPFS were unmatured and 8.1 months, respectively.

In terms of safety, the grade 3 and higher treatment-related TEAEs (TRAEs) occurred in 51% of the patients, and serious TRAEs occurred in 28%. The most common TRAE were leukopenia (G≥3 29%), anemia (G≥3 22%) and neutropenia (G≥3 30%), while decreased appetite (G≥3 1%) and nausea (G≥3 1%) were the most common non-hematological TRAEs. Only 3 (1%) were reported as treatment related interstitial lung disease.

"We are excited to share the results of YL201 at the ESMO (Free ESMO Whitepaper) Congress," said Dr. Steve Chin, Chief Medical Officer of MediLink. "Clinical data accumulated from a sample size of over 300 patients has solidly demonstrated the antitumor activity of YL201 in multiple solid tumor types, especially in SCLC, NPC, and NSCLC without AGA. Significant improvement was shown in these population compared to historical data of existing standard treatment regimens. Also, YL201 is well tolerated with the most common TRAEs being hematological toxicities, which are deemed to be manageable. We were actively preparing Phase 3 studies of YL201 in SCLC, NPC, etc."

About YL201

YL201 is an innovative antibody-drug conjugate that specifically targets B7-H3. B7-H3 is overexpressed on differentiated malignant cells and cancer-initiating cells of various tumor types, but has a restricted expression in normal tissue, indicating its potential as ADC drug. YL201 has been developed by utilizing MediLink’s Tumor Microenvironment Activable LINker-payload (TMALIN) conjugated with a highly specific B7-H3 antibody. Currently, YL201 is being investigated in four Phase I or II studies, including one multi-national Phase I clinical study.