FDA Grants Fast Track Designation to CUSP06 for Platinum-Resistant Ovarian Cancer

The FDA has granted fast track designation to CUSP06, a CDH6-directed antibody-drug conjugate (ADC), for the treatment of patients with platinum-resistant ovarian cancer.1

The agent is being evaluated in the ongoing, phase 1a/1b CUSP06-1001 trial (NCT06234423) in patients with platinum-refractory/-resistant ovarian cancer, advanced renal cell carcinoma (RCC), and other advanced CDH6-positive solid tumors.2 In March 2024, the company developing the agent, OnCusp Therapeutics, announced that the first patient had been dosed in the trial.3 Preliminary data from the trial have shown encouraging efficacy and a manageable safety profile, according to the news release.1

“We are extremely pleased that the FDA granted fast track designation to CUSP06,” Eric Slosberg, PhD, chief development officer of OnCusp Therapeutics, stated 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.”

CDH6 is a transmembrane glycoprotein involved in cancer metastasis and invasion that can be found in ovarian cancer, RCC, papillary thyroid cancer, cholangiocarcinoma, sarcoma, and uterine serous carcinoma.2 CUSP06 is an ADC designed with a human IgG1 monoclonal antibody directed against CDH6 conjugated with a protease-cleavable linker, T100, to the topoisomerase I inhibitor payload exatecan.

In preclinical models, CUSP06 exhibited CDH6-dependent cell growth inhibition in ovarian cancer cell lines. Moreover, tumor regression was seen in both ovarian and renal cell line–derived xenograft and patient-derived xenograft (PDX) models with high CDH6 expression, as well as low CDH6-expressing PDX models of other solid tumors.

The first-in-human, open-label, multi-center, dose-escalation and -expansion trial is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, recommended phase 2 dose, and preliminary efficacy of CUSP06. Phase 1a will follow a standard 3+3 dose escalation design with 1 patient in cohort 1. Up to 3 dose enrichment cohorts will be added at doses that have shown safety, with up to 18 patients in each cohort. Phase 1b will be comprised of 4 expansion cohorts including platinum-resistant/-refractory ovarian cancer, RCC, and other CDH6-positive tumors according to a Simon’s 2-stage design. Cohort selection will be informed by data from phase 1a.

To be eligible for enrollment patients need to be at least 18 years of age and have histologically or cytologically confirmed advanced solid tumors previously treated with standard of care systemic therapy, or for whom no standard therapy is available; an ECOG performance status of 0 or 1; and a life expectancy of at least 12 weeks. CDH6 prescreening will be required for all tumor types except for ovarian cancer and RCC.

Patients who previously received an ADC with a topoisomerase I payload or underwent allogeneic bone marrow transplant will be excluded from enrollment. Other exclusion criteria include active or progressing brain metastases or evidence of leptomeningeal disease, major surgery within 4 weeks of the first study dose, clinically significant lung disease requiring systemic corticosteroid treatment within the past 6 months, hepatic insufficiency, hepatic encephalopathy, and/or variceal bleed within 60 days prior to study entry, and history of liver transplant, significant cardiac disease, or thromboembolic/cerebrovascular events within 3 months prior to the first study dose.

Eligible patients will receive CUSP06 intravenously once every 21 days.

References

1. OnCusp Therapeutics receives FDA fast track designation for CUSP06 for the treatment of platinum-resistant ovarian cancer. News release. OnCusp Therapeutics, Inc. February 12, 2025. Accessed February 12, 2025. https://www.oncusptx.com/html/companynews/103.html
2. Spira AI, Lee EK, O’Cearbhaill RE, et al. A phase 1, first-in-human study of CUSP06, a cadherin-6 (CDH6) -directed antibody-drug conjugate, in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors. J Clin Oncol. 2024;42(suppl 16):TPS3166. doi:10.1200/JCO.2024.42.16_suppl.TPS3166
3. OnCusp Therapeutics announces first patient dosed in phase 1 trial of CUSP06 in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors. News release. OnCusp Therapeutics. March 6, 2024. Accessed February 12, 2025. https://www.oncusptx.com/html/companynews/75.html