Currently, the Cadherin-6 targeting antibody-drug conjugate is undergoing evaluation in a phase 1a/1b clinical trial.
The FDA has granted fast track designation to CUSP06 (AMT-707; OnCusp Therapeutics) for the treatment of patients with platinum-resistant ovarian cancer. The agent is currently undergoing evaluation in the phase 1a/1b clinical trial, CUSP06-1001 (NCT06234423).1,2
CUSP06 is a Cadherin-6 targeting antibody-drug conjugate (CDH6 ADC) that is composed of a proprietary antibody with high CDH6 binding affinity, a protease-cleabable linker, as well as an exatecan payload, which is a potent and clinically validated topoisomerase-1 inhibitor. The linker is designed to complement the exatecan payload, allowing for a stable and homogenous ADC. Additionally, the payload is a weak substrate for BCRP/P-gp. In preclinical data, this linker payload demonstrated to have an increased “bystander effect” compared with other ADCs.1
The first-in-human, multicenter, open-label phase 1a/1b CUSP06-1001 clinical trial (NCT06234423) is ongoing to evaluate the safety, tolerability, pharmacokinetics, and efficacy of CUSP06 in patients aged 18 and older with platinum-refractory or resistant ovarian cancer, as well as other advanced solid tumors. An estimated 180 patients with advanced solid tumors or ovarian cancer will be enrolled and receive CUSP06 intravenously every 21 days, according to the investigators.2,3
Patients with advanced solid tumors who were previously treated with standard of care systemic therapy, as well as those for whom no standard therapy was available, are eligible for trial enrollment. Additionally, patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 and a life expectancy of at least 12 weeks were also eligible. After enrollment, participants with solid tumors (eg, papillary thyroid cancer, cholangiocarcinoma, hepatocellular cancer, glioma, uterine serous carcinoma, and non-small cell lung cancer) that are not platinum-refractory or resistant ovarian cancer or renal cell carcinoma (RCC) will be required to complete prescreening for CDH6 expression.2,3
The trial’s phase 1a portion will follow a standard 3+3 dose escalation design and include up to 3 dose enrichment cohorts—with a minimum of 18 patients—at doses that have shown safety to generate additional safety, pharmacokinetic, pharmacodynamic, and preliminary efficacy data to support an optimized dose for expansion. The phase 1b portion consists of several dose expansion cohorts, including platinum-refractory or resistant ovarian cancer, RCC, as well as other CDH6-positive solid tumors.3
Trial Name: A Study of CUSP06 in Patients With Platinum-Refractory/Resistant Ovarian Cancer and Other Advanced Solid Tumors
ClinicalTrials.gov ID: NCT06234423
Sponsor: OnCusp Therapeutics, Inc.
Completion Date (Estimated): August 31, 2027
The trial’s primary end points were the characterization of safety and tolerability of CUSP06 (phases 1a and 1b), the recommended dose for expansion (phase 1a), and preliminary efficacy of CUSP06 (measured by objective response rate; phase b). Secondary end points included pharmacokinetics, such as maximum concentration (Cmax) time to Cmax, area under the curve, disease control rate, clinical benefit rate, duration of response, time to progression, as well as others, all of which were end points for phases 1a and 1b.2
"We are extremely pleased that the FDA granted [a] fast track designation to CUSP06," said Eric Slosberg, PhD, chief development officer of OnCusp Therapeutics, in a news release. "The early results from our phase 1 trial have been encouraging, and this designation will expedite our efforts to bring this potentially transformative therapy to patients. Given the need for new therapeutic options in this underserved population, we are committed to working closely with the FDA to accelerate its development."1
