FDA Fast Tracks CUSP06 in Platinum-Resistant Ovarian Cancer

• The FDA has granted fast track designation to CUSP06 for the treatment of patients with platinum-resistant ovarian cancer.
• CUSP06 is a CDH6-directed antibody-drug conjugate (ADC).
• The agent is currently undergoing evaluation in the phase 1a/1b CUSP06-1001 trial (NCT06234423).

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

The ongoing phase 1a/1b CUSP06-1001 trial (NCT06234423) is evaluating the agent when given as a treatment in patients with platinum-refractory/resistant ovarian cancer, advanced renal cell carcinoma (RCC), and other advanced CDH6-positive solid tumors.²

Preliminary data from the trial showed the agent to elicit encouraging efficacy and a manageable safety profile, supporting further development of the program. In March 2024, it was also announced that the first patient was dosed in the trial.³

“We are extremely pleased that the FDA granted fast track designation to CUSP06,” said Eric Slosberg, PhD, chief development officer of OnCusp Therapeutics, in a news release.¹ “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.”

Illustration of ovarian cancer: © blueringmedia - stock.adobe.com

CUSP06-1001 is a first-in-human, open-label, multicenter, dose-escalation and dose-expansion study of CUSP06.⁴ Experts are assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, recommended phase 2 dose, and preliminary efficacy of the agent.

Enrollment in the study is open to patients aged 18 years and older with histologically or cytologically confirmed advanced solid tumors previously treated with standard of care systemic therapy, or for whom no standard therapy is available. Patients must also have an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and are required to undergo CDH6 prescreening for all tumor types except for ovarian cancer and RCC.

Phase 1a will use a 3+3 dose escalation design, starting with 1 patient in cohort 1. Up to 3 additional dose enrichment cohorts will be added at safe doses, with up to 18 patients per cohort. Phase 1b will include 4 expansion cohorts for platinum-resistant/refractory ovarian cancer, RCC, and other CDH6-positive tumors, following a Simon’s 2-stage design. Cohort selection will be based on phase 1a data. Eligible patients will receive CUSP06 intravenously 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 13, 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 13, 2025. https://www.oncusptx.com/html/companynews/75.html

4. A study of CUSP06 in patients with platinum-refractory/​resistant ovarian cancer and other advanced solid tumors. ClinicalTrials.gov. Updated August 19, 2024. Accessed February 13, 2025. https://clinicaltrials.gov/study/NCT06234423