Daiichi Sankyo Company, Limited and Sarah Cannon Research Institute (Sarah Cannon) announced that initial results from the first-in-human phase 1 study of DS-6000, a CDH6 directed DXd antibody drug conjugate (ADC), suggest early clinical activity in patients with advanced ovarian cancer or renal cell carcinoma with disease progression following standard of care treatment. The data were presented in an oral session (Abstract #3002) at the American Society of Clinical Oncology (#ASCO22) Annual Meeting. Patients with advanced ovarian cancer or renal cell carcinoma may have disease progression after initial treatments and there is a need for new therapeutic approaches for recurrent disease, as five-year survival rates in the U.S. are low at 30% and 15%, respectively.

The CDH6 protein is significantly overexpressed in ovarian cancer and renal cell carcinoma and has been identified as a promising therapeutic target. Preliminary safety and efficacy results of DS-6000 were reported from the dose escalation part of the phase 1 trial in 30 heavily pretreated patients, including 21 patients with advanced ovarian cancer, one of which was missing a primary diagnosis of ovarian cancer, and nine patients with renal cell carcinoma. The safety and tolerability of DS-6000 was evaluated at increasing dose levels from 1.6 mg/kg to 9.6 mg/kg with two dose-limiting toxicities observed at the 9.6 mg/kg dose (grade 3 febrile neutropenia and grade 4 thrombocytopenia).

The most common treatment-related emergent adverse events (TEAEs) (= 10% of patients) reported were nausea (60.0%), fatigue (56.7%), vomiting (30.0%), neutrophil count decrease (23.3%), decreased appetite (20.0%), and diarrhea (13.3%). Grade = 3 TEAEs occurred in seven patients (23.3%), the most common of which were neutrophil count decrease (16.7%), anemia (6.7%) and febrile neutropenia (6.7%). One patient experienced grade 2 pneumonitis at the 9.6 mg/kg dose that led to treatment discontinuation.

Preliminary efficacy results in 20 evaluable patients included six partial responses (PRs) in patients with ovarian cancer (n=5) and renal cell carcinoma (n=1). Four PRs were confirmed and two are awaiting confirmation. Stable disease was reported in 12 patients with platinum-resistant ovarian cancer.

Eight CA-125 responses were observed in 17 evaluable patients with ovarian cancer, based on the Gynecologic Cancer Intergroup (GCIG) criteria. All patients enrolled in the study (n=30) had received a median of three prior lines of systemic therapies (range, 1-12), including four (range, 1-12) for patients with ovarian cancer and two (range, 1-6) for patients with renal cell carcinoma. Seventeen of the 20 patients with ovarian cancer had platinum-resistant disease.

As of the data cut-off on February 25, 2022, 17 patients (56.7%) were still being treated with DS-6000 including 12 patients with ovarian cancer and five patients with renal cell carcinoma.