OnCusp CUSP06 hits 62% response rate in resistant ovarian cancer
OnCusp Therapeutics has reported initial Phase 1b data for CUSP06, its Cadherin-6 (CDH6)-directed antibody-drug conjugate (ADC), in platinum-resistant ovarian cancer (PROC). Presented as a plenary oral at the International Gynecologic Cancer Society 2026 Annual Global Meeting in Montreal on 3 October, the data showed a 62% objective response rate (ORR) in 21 patients treated at the 4.0 mg/kg dose level, including three complete responses, as of a 23 September data cutoff.
Across all four dose cohorts evaluated in 81 efficacy-evaluable patients, ORRs ranged from 40% to 62%. A 53% ORR was observed in the 30 patients who had previously received mirvetuximab soravtansine, the folate receptor-alpha-targeting ADC approved by the FDA in 2022 and currently the standard of care for a subset of PROC patients. That cross-over activity is commercially significant: it suggests CUSP06 could address a population for whom mirvetuximab has already failed, broadening its potential addressable market.
Safety and mechanism
CUSP06 carries an exatecan topoisomerase-1 (TOP1) inhibitor payload via a protease-cleavable linker, with a drug-to-antibody ratio of eight. The safety profile in 86 Phase 1b PROC patients was characterised primarily by haematological toxicities, including anaemia, neutropenia and thrombocytopenia, consistent with the class effect seen across TOP1-inhibitor ADCs. The company reported no ocular toxicity and a pneumonitis rate of just 1% (one case in 86 patients).
The absence of ocular toxicity and the low pneumonitis rate will draw attention from clinicians. Both events have been associated with other high-profile ADCs in the clinic. Roisin E. O'Cearbhaill, the presenting investigator from Memorial Sloan Kettering Cancer Center, noted that the low pneumonitis incidence "may suggest a potential safety advantage compared with other TOP1 inhibitor-based ADCs," while cautioning that the results remain early.
Median duration of response from the Phase 1a high-grade serous ovarian cancer cohort was 10.5 months, with the longest response exceeding 23 months and still ongoing at cutoff.
Competitive landscape and regulatory path
CDH6 is expressed across a range of solid tumours, and OnCusp is also evaluating CUSP06 in advanced renal cell carcinoma and other CDH6-positive cancers under the same Phase 1 protocol (NCT06234423). That positions the asset as a potential platform beyond PROC if the antigen's expression profile proves tractable.
The ADC sector broadly remains one of the most competitive areas of oncology development, with multiple large-cap pharma companies holding approved or late-stage assets. Within CDH6 targeting specifically, the field is less crowded, though interest has grown following clinical validation of the target in gynaecological oncology. CUSP06 received FDA Fast Track designation for PROC, which accelerates review timelines and enables more frequent agency interactions.
OnCusp, headquartered in Princeton, New Jersey, has raised $139 million across seed and Series A rounds from investors including Novo Holdings, OrbiMed and F-Prime Capital. The company said it intends to advance CUSP06 into pivotal-stage testing, though no Phase 2 or Phase 3 trial design or timeline was announced alongside the data readout. Investors will be watching for clarity on the registrational path and any update on the renal cell carcinoma cohort, where CDH6 expression data could open a second substantial indication.