MediLink Therapeutics is advancing YL201, a novel B7H3-targeting antibody-drug conjugate (ADC), as a potential treatment for various solid tumors, including small cell lung cancer (SCLC), nasopharyngeal carcinoma (NPC), and non-small cell lung cancer (NSCLC). Clinical data from Phase I studies, presented at the European Society for Medical Oncology (ESMO) Congress 2024, demonstrate encouraging antitumor activity and manageable safety profiles. Furthermore, a global clinical trial collaboration with Amgen aims to evaluate YL201 in combination with Amgen's IMDELLTRA™ in extensive-stage SCLC (ES-SCLC).
YL201 Monotherapy Shows Promise in SCLC and Other Tumors
The Phase I studies (NCT05434234 & NCT06057922) enrolled 312 patients with advanced solid tumors across multiple sites in China and the US. All patients had received prior standard therapy, with 60% having undergone at least two prior treatment lines. The data, cut off August 9, 2024, revealed an overall response rate (ORR) of 44.6% and a disease control rate (DCR) of 83.7% across all tumor types. The median follow-up duration was 5.4 months, with 46% of patients remaining on treatment.
In the subgroup of patients with extensive-stage SCLC (n=72), all of whom had prior treatment with platinum-based chemotherapy and 95% with anti-PD-(L)1 therapy, YL201 demonstrated an ORR of 68.1% (70.0% at dose levels >= 2.0 mg/kg) and a median progression-free survival (mPFS) of 6.2 months (6.2 months at dose levels >= 2.0 mg/kg). Notably, patients with brain metastasis also showed a comparable response, with an ORR of 52.2% and mPFS of 5.3 months.
Activity in Nasopharyngeal Carcinoma and NSCLC
YL201 also exhibited activity in 70 evaluable NPC patients, with an ORR of 48.6% (48.6% at dose levels >= 2.0 mg/kg) and an mPFS of 7.2 months (7.2 months at dose levels >= 2.0 mg/kg). In heavily pre-treated NPC patients who had received at least two prior lines of treatment, the efficacy remained comparable, with an ORR of 51.0% and an mPFS of 7.0 months.
In NSCLC patients without actionable genomic alterations, all of whom had prior treatment with anti-PD-(L)1 and platinum-based chemotherapy, the ORR in adenocarcinoma and LELC subtypes were 29.2% and 60.9%, respectively, with mPFS being unmatured and 8.1 months, respectively.
Safety Profile
The most common treatment-related adverse events (TRAEs) of grade 3 or higher were hematological toxicities, including leukopenia (29%), anemia (22%), and neutropenia (30%). Non-hematological TRAEs were less frequent, with decreased appetite and nausea each occurring in only 1% of patients. Treatment-related interstitial lung disease was reported in only 1% of patients.
Collaboration with Amgen for Combination Therapy in ES-SCLC
MediLink has entered into a global clinical trial collaboration and supply agreement with Amgen to evaluate the combination of YL201 and Amgen's DLL3- and CD3-targeting bispecific T-cell engager (BiTE®) IMDELLTRA™ in ES-SCLC. This open-label, multi-center Phase Ib clinical study will assess the safety, tolerability, pharmacokinetics, and efficacy of the combination regimen.
IMDELLTRA™ received accelerated approval from the FDA in May 2024 for the treatment of adult patients with ES-SCLC with disease progression on or after platinum-based chemotherapy. The collaboration aims to explore the potential synergistic effects of the two innovative drugs in treating ES-SCLC.
Mechanism of Action and Future Directions
YL201 targets B7-H3, a protein overexpressed on various tumor types but with limited expression in normal tissue, making it an attractive target for ADC development. YL201 utilizes MediLink's Tumor Microenvironment Activable LINker-payload (TMALIN®) technology. According to Dr. Steve Chin, Chief Medical Officer of MediLink, the company is actively preparing Phase 3 studies of YL201 in SCLC and NPC.
