Daiichi Sankyo has announced positive initial findings from the dose escalation phase of its Phase I clinical trial of DS-9606, an investigational antibody-drug conjugate (ADC) for advanced solid tumors. The trial, a first-in-human study, assessed the safety, tolerability, and preliminary efficacy of DS-9606 in heavily pretreated patients with various cancers.
DS-9606: Targeting CLDN6 in Solid Tumors
DS-9606, developed using Daiichi Sankyo's second ADC technology platform in collaboration with the Tokyo University of Pharmacy and Life Sciences, comprises a humanized Claudin-6 (CLDN6) monoclonal antibody linked to a modified pyrrolobenzodiazepine (PBD) payload. CLDN6 is a protein expressed in several tumor types, including endometrial, ovarian, gastric cancers, germ cell tumors, and non-small cell lung cancer.
Phase I Trial Details and Results
The Phase I trial involved 53 heavily pretreated patients with various cancers who had undergone a median of four prior therapies. Doses of DS-9606 ranged from 0.016 mg/kg to 0.225 mg/kg. The safety profile was deemed acceptable, with no dose-limiting toxicities observed and no patients withdrawing due to treatment-related adverse events. The most common treatment-emergent adverse events (TEAEs) included nausea, fatigue, and anaemia, with Grade 3 or higher TEAEs occurring in 30.2% of patients.
Preliminary efficacy results showed four confirmed objective responses at doses greater than or equal to 0.072mg/kg. Notably, two responses were observed in patients with germ cell tumors, and one response each in patients with gastric/esophageal cancer and non-small cell lung cancer. Seven patients with germ cell tumors showed significant tumor marker reductions, with two maintaining treatment response for over six months. As of the data cutoff on 14 June 2024, 21 patients continue to receive DS-9606 treatment.
Future Directions
The ongoing Phase I trial is evaluating the drug's safety, tolerability, and efficacy in adult patients with CLDN6-expressing advanced solid tumors in Europe and North America. The trial's next steps include determining the maximum tolerated dose and the recommended dose for expansion, followed by further evaluation in dose expansion cohorts.
Ken Takeshita, Daiichi Sankyo R&D global head, stated, "While these results provide preliminary proof-of-concept for DS-9606, further clinical evaluation is warranted across different tumor types that are known to express CLDN6. We continue to apply our science and technology expertise to DS-9606, which has been developed from our second antibody-drug conjugate platform in order to create potentially new and innovative treatments for certain patients with cancer."
