OnCusp Therapeutics Announces Positive Phase 1b Data Evaluating its CDH6-Directed Antibody-Drug Conjugate, CUSP06, in Platinum-Resistant Ovarian Cancer (PROC) Presented at Plenary Oral Session of the IGCS 2026 Annual Global Meeting

Initial Phase 1b data highlight promising clinical activity in patients with PROC and support continued clinical development of CUSP06

At the September 23, 2026, data cutoff, CUSP06 achieved a 62% objective response rate (ORR) in patients treated at 4.0mg/kg in Phase 1b with response and durability data continuing to mature

Robust activity observed in patients previously treated with mirvetuximab soravtansine, with a 53% ORR

CUSP06 demonstrated a manageable safety profile, with primarily hematologic toxicities, no ocular toxicity, and infrequent low-grade pneumonitis (1%) in Ph1b PROC cohorts

PRINCETON, N.J., Oct. 05, 2026 (GLOBE NEWSWIRE) -- OnCusp Therapeutics, Inc., a clinical-stage biopharmaceutical company developing differentiated therapies designed to translate cutting-edge innovation into clinically meaningful outcomes for patients, today announced initial data from the Company’s Phase 1b open-label, multicenter dose-expansion study evaluating its Cadherin-6 (CDH6)-directed antibody-drug conjugate (“ADC”), CUSP06, for the treatment of platinum-resistant ovarian cancer (“PROC”). The Phase 1b data are being presented for the first time by Roisin E. O’Cearbhaill, M.D., Gynecological Medical Oncologist and Cellular Therapist, Memorial Sloan Kettering Cancer Center, at a plenary oral session of the International Gynecologic Cancer Society (IGCS) 2026 Annual Global Meeting, on October 3, 2026, at Palais des Congrès de Montréal in Montréal, Canada.

“We are excited to report these initial data from our Phase 1b trial at this year’s IGCS Annual Meeting, which reflect the potential of CUSP06 to treat platinum-resistant ovarian cancer in patients who have experienced disease progression after multiple lines of prior therapy,” said Dr. Bing Yuan, Co-Founder and CEO of OnCusp Therapeutics. “The 62% ORR observed in the 4.0 mg/kg cohort represents one of the highest response rates reported in PROC patients receiving an experimental TOP1-inhibitor ADC. CUSP06 also demonstrates robust activity in patients previously treated with mirvetuximab soravtansine. Importantly, CUSP06 continues to maintain an acceptable safety and tolerability profile in line with other TOP1 inhibitor ADCs currently in development. We believe these Phase 1b data provide us with strong clinical evidence that CUSP06 is a very active, differentiated and potentially best-in-class CDH6-targeting ADC in ovarian cancer and possibly other CDH6-expressing cancers.”

“Despite advances in treatment, most patients with ovarian cancer will ultimately develop resistance to platinum-based chemotherapy, highlighting the need for new therapeutic approaches," said Dr. Roisin E. O'Cearbhaill. "The development of highly potent antibody-drug conjugates targeting CDH6, which is frequently overexpressed in ovarian cancer, represents a promising strategy for patients with recurrent and treatment-resistant disease. I am particularly encouraged not only by the response rates observed in this study, but also by the duration of response and the low incidence of pneumonitis, which may suggest a potential safety advantage compared with other TOP1 inhibitor-based ADCs. While these results remain early, the overall findings from this Phase 1b study support the continued development of CUSP06, and I look forward to seeing the program advance into pivotal-stage clinical testing."

The Phase 1b trial (NCT06234423) is an open-label multi-center, dose- expansion study evaluating CUSP06 in patients with platinum-refractory/resistant ovarian cancer (PROC), advanced renal cell carcinoma (RCC) and other CDH6-positive solid tumors. More specifically, the Phase 1b portion of the trial included data from 86 heavily pre-treated PROC patients with a median of 3 lines of prior therapy. Eligibility included patients with high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer which is platinum-resistant with 1-4 prior lines of therapy.

Four cohorts treated with CUSP06 were evaluated in the Phase 1b trial: 3.6 mg/kg (n=22), 4.0 mg/kg (n=21), 4.0 mg/kg + prophylactic G-CSF (n=20), and 4.4 mg/kg + prophylactic G-CSF (n=23).

The primary endpoint of the Phase 1b study was Objective Response Rate (ORR) based on RECIST v1.1, safety parameters (incidence/severity of AEs and SAEs, frequency and duration of dose modifications). Secondary endpoints included Clinical Benefit Rate (CBR), Disease Control Rate (DCR), Duration of Response (DOR), Time to Progression (TTP), Progression Free Survival (PFS) as measured by RECIST v1.1, and Pharmacokinetic (PK) parameters.

As of September 23, 2026, there were 81 Ph1B PROC patients evaluable for efficacy in the trial.

Summary of efficacy data

CUSP06 demonstrated meaningful responses across dose levels in the four patient cohorts, including complete responses (CR):

• 50% ORR (10/20) in the 3.6 mg/kg cohort; including 1 CR
• 62% ORR (13/21) in the 4.0 mg/kg cohort; including 3 CR
• 45% ORR (9/20) in the 4.0 mg/kg + G-CSF cohort
• 40% ORR (8/20) in the 4.4 mg/kg + G-CSF cohort; including 1 CR
  
  
• 53% ORR (16/30) in post-mirvetuximab treated patients; including 1 CR
• mDOR from the Phase 1a part of the study HGSOC was 10.5 months, with longest response > 23 months (ongoing)

Data from the ongoing Phase 1b study continues to mature, which could provide additional evidence in support of CUSP06 as a potential best-in-class TOP1 ADC therapy for the treatment of PROC.

Summary of safety and tolerability data  

• Most common TRAEs were hematologic (anemia, neutropenia, thrombocytopenia), GI (nausea, vomiting, diarrhea), and fatigue, consistent with TOP1 inhibitor ADC class effects
• Dose modifications were primarily driven by hematologic AEs, consistent with mechanism, and were manageable
• No ocular toxicity reported
• Pneumonitis rate remains rare with only 1 case in 86 patients

Presentation Details:
Title: Dose-Optimization, Efficacy, and Safety of CUSP06, a Cadherin-6 Directed Antibody-Drug Conjugate, in Platinum-Resistant Ovarian Cancer
Session Title: Plenary Oral 2
Abstract Number: 503 

CUSP06 has been granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of patients with platinum-resistant ovarian cancer.

About CUSP06

CUSP06 is a Cadherin-6 (CDH6)-targeting antibody-drug conjugate (ADC) now in the Phase 1b portion of a Phase 1 study in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors. CUSP06 has shown promising efficacy in heavily pretreated ovarian cancer, with both Phase 1a and Phase 1b results supporting potential best-in-class activity. CUSP06 is composed of a proprietary antibody with high CDH6 binding affinity, a protease-cleavable linker, and an exatecan payload (a potent and clinically validated topoisomerase-1 inhibitor). The linker is designed to complement the exatecan payload, enabling a stable and homogeneous ADC. The payload is a weak substrate for BCRP/P-gp, drug efflux pumps that drive chemoresistance to many therapies. In preclinical data, CUSP06’s linker-payload has been shown to have an increased “bystander effect” compared with competitor ADCs. CUSP06 has a drug-to-antibody ratio of eight. OnCusp obtained the exclusive global rights (outside of China) to lead the development and commercialization of CUSP06 from Multitude Therapeutics in 2022. Additional information on the CUSP06-1001 (NCT06234423) trial can be found at ClinicalTrials.gov.

About OnCusp Therapeutics

OnCusp Therapeutics, Inc., is a clinical-stage biopharmaceutical company dedicated to transforming cutting-edge preclinical innovation into clinically meaningful outcomes for patients. The company’s lead program, CUSP06—a Cadherin-6 (CDH6)-targeting antibody-drug conjugate (ADC)—is in the final stage of the Phase 1b study in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors. OnCusp Therapeutics raised a total of $139M in Seed and Series A fund raising, supported by leading investors such as Novo Holdings, OrbiMed, and F-Prime Capital. OnCusp is headquartered in Princeton, New Jersey. For more information, visit www.oncusptx.com.

CONTACTS:

Anthony H. Kim
Chief Financial Officer
OnCusp Therapeutics
investors@oncusptx.com

John P. Fraunces
Managing Director
LifeSci Advisors, LLC
jfraunces@lifesciadvisors.com