DS-9606 Shows Promising Activity in Advanced Solid Tumors

Initial results from the dose escalation phase of the first-in-human clinical trial for DS-9606, a modified pyrrolobenzodiazepine (PBD) antibody drug conjugate (ADC) targeting Claudin-6 (CLDN6), indicate promising clinical activity in patients with advanced solid tumors. Presented at the 2024 European Society for Medical Oncology (ESMO24), these findings highlight the potential of DS-9606 in treating various cancers known to express CLDN6, including endometrial, ovarian, gastric, germ cell tumors (GCT), and non-small cell lung cancer (NSCLC).

DS-9606, developed by Daiichi Sankyo, is part of their second ADC platform and is designed to target CLDN6, which is often associated with poor prognosis in several tumor types. The initial phase 1 trial involved 53 patients who had undergone extensive previous treatments, with a median of four prior therapies (ranging from one to nine). The group included patients with ovarian cancer (19), GCT (11), gastric/esophageal cancer (7), NSCLC (7), pancreatic cancer (5), breast cancer (2), and endometrial cancer (2).

The safety and tolerability of DS-9606 were tested at increasing doses from 0.016 mg/kg to 0.225 mg/kg. No dose-limiting toxicities were reported, and no patients withdrew due to treatment-related adverse events. Common side effects included nausea, fatigue, anemia, abdominal pain, constipation, vomiting, diarrhea, fever, weight loss, reduced appetite, joint pain, cough, sinusitis, shortness of breath, and pleural effusion. Grade 3 or higher adverse events occurred in 30.2% of patients, with anemia, abdominal pain, pleural effusion, constipation, vomiting, and diarrhea among the more severe cases. Skin-related side effects were also noted, with most being mild except for some grade 2 and 3 events.

Preliminary efficacy of DS-9606 was observed at doses of 0.072 mg/kg and above (excluding 0.190 mg/kg due to immature data). Four objective responses were confirmed, including two in GCT patients and one each in gastric/esophageal cancer and NSCLC patients. Among the seven evaluable GCT patients, two maintained treatment for over six months, and five showed significant reductions in tumor markers. As of the data cutoff on June 14, 2024, 21 patients were still receiving DS-9606.

Dr. Manish R. Patel from Florida Cancer Specialists and Sarah Cannon Research Institute emphasized the encouraging results, particularly for GCT patients, and announced ongoing enrollment to further determine the optimal dose and understand the broader impact on other advanced solid tumors. Ken Takeshita, Global Head of R&D at Daiichi Sankyo, also noted that these findings provide early proof-of-concept for DS-9606, motivating further clinical evaluation across different CLDN6-expressing tumors.

The ongoing phase 1 trial is a multicenter, open-label study assessing the safety, tolerability, and efficacy of DS-9606. The dose escalation phase aims to identify the maximum tolerated dose and/or recommended dose for expansion. Following this, the dose expansion phase will further evaluate the drug's safety, tolerability, and effectiveness in specific cohorts of advanced solid tumors based on initial data.

This trial will measure various endpoints, including objective response rate, duration of response, and progression-free survival, along with pharmacokinetic and immunogenicity assessments. Currently, the trial is enrolling patients in Europe and North America.

DS-9606 represents an innovative approach in Daiichi Sankyo's ADC portfolio, which includes seven ADCs in clinical development. The portfolio features two distinct technology platforms, with DS-9606 being the first to utilize the second platform targeting CLDN6.